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Zhang C, Yuan M, Rong W, Du H, Li X, Ji T, Li J, Dai B, Ma Z, Qi H, Zhang N, Yang J, Duan X, Bi Y. Synergistic effects of Lianhuaqingwen in combination with Oseltamivir and Baloxavir against seasonal influenza virus: In vitro and in vivo assessment. JOURNAL OF ETHNOPHARMACOLOGY 2025; 338:119091. [PMID: 39528119 DOI: 10.1016/j.jep.2024.119091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/06/2024] [Accepted: 11/08/2024] [Indexed: 11/16/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Lianhuaqingwen (LH), a traditional Chinese medicine, presents a broad-spectrum antiviral effect and has been widely used to treat influenza. Given the potential rise of drug-resistant influenza viruses, it is necessary to develop new antiviral drugs and explore combination therapies involving LH in tandem with existing antivirals such as Oseltamivir acid (Osel) or Baloxavir (Bal). These multidrug combinations could help effectively control the seasonal influenza epidemics and reduce the disease burden. AIM OF THE STUDY This study aimed to evaluate the antiviral effects of LH, alone and in combination with Osel or Bal, against human seasonal influenza viruses in vitro and in vivo models. MATERIALS AND METHODS The antiviral efficacy of LH alone and LH in combination with Osel/Bal against seasonal influenza A viruses (IAVs) (H1N1 and H3N2 subtypes) and influenza B viruses (IBVs) (BV- and BY-lineages) was assessed in vitro using MDCK cells. The median effective concentration (EC50) was determined, and the drug synergies were analyzed. Additionally, the antiviral activity of LH monotherapy and LH + Osel/Bal combination therapy were evaluated in vivo using an H1N1-infected BABL/c mouse model by monitoring changes in body weight, survival rate, lung viral titer, pathological damage, and inflammatory reaction. RESULTS In vitro, LH alone and in combination with Osel/Bal exhibited antiviral activity against both IAVs and IBVs. The addition of LH to Osel/Bal improved the therapeutic efficacy compared to Osel/Bal alone. In vivo, LH monotherapy reduced body weight loss and increased the survival rates of H1N1-infected mice. LH in combination with Osel/Bal resulted in lower virus titers, more effective relief of pathological damage, and comparable low expression of inflammatory factors in the lungs of H1N1-infected mice compared to the use of Osel/Bal alone. Transcriptomic analysis of the lungs revealed that LH + Osel/Bal significantly increased the expression of genes associated with antiviral and anti-inflammatory effects. CONCLUSIONS This study evaluated the antiviral effects of LH monotherapy and combination therapy with Osel/Bal against human seasonal influenza viruses in vitro and in vivo models. The results suggest that combining LH with Osel or Bal could enhance the antiviral efficiency for influenza viruses compared to the monotherapy using any of these three drugs.
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Affiliation(s)
- Cheng Zhang
- College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China
| | - Manhua Yuan
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China
| | - Wenwan Rong
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Han Du
- College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China
| | - Xuanxuan Li
- College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China
| | - Tiannan Ji
- Department of Emergency, Department of Radiotherapy, The Fifth Medical Center of PLA General Hospital, Beijing, 100071, China
| | - Jianxiong Li
- Department of Emergency, Department of Radiotherapy, The Fifth Medical Center of PLA General Hospital, Beijing, 100071, China
| | - Bo Dai
- Department of Pharmacy, Air Force Medical Center, PLA, Beijing, 100142, China
| | - Zhenghai Ma
- College of Life Science and Technology, Xinjiang University, Urumchi, 830046, China
| | - Hui Qi
- Hebei Academy of Integrated Traditional Chinese and Western Medicine, National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, China
| | - Ning Zhang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China
| | - Jing Yang
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China
| | - Xuefeng Duan
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuhai Bi
- CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
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Alqaraleh M, Khleifat KM, Al-Samydai A, Al-Najjar BO, Saqallah FG, Al Qaisi YT, Alsarayreh AZ, Alqudah DA, Fararjeh AS. Bioactive potency of extracts from Stylissa carteri and Amphimedon chloros with silver nanoparticles against cancer cell lines and pathogenic bacteria. Biomed Rep 2025; 22:34. [PMID: 39777210 PMCID: PMC11704841 DOI: 10.3892/br.2024.1912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 10/15/2024] [Indexed: 01/11/2025] Open
Abstract
Silver nanoparticles (AgNPs) are spherical particles with a number of specific and unique physical (such as surface plasmon resonance, high electrical conductivity and thermal stability) as well as chemical (including antimicrobial activity, catalytic efficiency and the ability to form conjugates with biomolecules) properties. These properties allow AgNPs to exhibit desired interactions with the biological system and make them prospective candidates for use in antibacterial and anticancer activities. AgNPs have a quenching capacity, which produces reactive oxygen species and disrupts cellular processes (such as reducing the function of the mitochondria, damaging the cell membrane, inhibiting DNA replication and altering protein synthesis). In addition, sponge extracts contain biologically active substances with therapeutic effects. Therefore, the concurrent use of these agents may present a potential for the development of novel antitumor and antimicrobial drugs. The present study investigated the cytotoxic effects of AgNPs combined with the extracts from sponge species, Stylissa carteri or Amphimedon chloros, against various cancer cell lines and pathogenic bacterial strains. The present study was novel as it provided a further understanding of the cytotoxicity and underlying mechanisms of AgNPs. Alterations in the properties, such as size, charge and polydispersity index, of the AgNPs were demonstrated after lyophilization. Scanning electron microscopy revealed submicron-sized particles. The cytotoxic potential of AgNPs across various cancer cell lines such as lung, colorectal, breast and pancreatic cancer cell lines, was demonstrated, especially when the AgNPs were combined with sponge extracts, which suggested a synergistic effect. Analysis using liquid chromatography-mass spectrometry revealed key chemical components in the extracts, and molecular docking simulations indicated potential inhibition interactions between a number of the extract components and the epidermal growth factor receptor and tyrosine kinase receptor A. Synergistic antibacterial effects against several bacterial species such as Staphylococcus xylosus, Klebsiella oxytoca, Enterobacter aerogenes, Micrococcus spp. and Escherichia coli, were observed when AgNPs were combined with sponge ethyl acetate extracts. The results of the present study suggested a potential therapeutic application of marine-derived compounds and nanotechnology in combating cancer and bacterial infections. Future research should further elucidate the mechanistic pathways and investigate the in vivo therapeutic efficacy.
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Affiliation(s)
- Moath Alqaraleh
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Balqa Applied University, Al-Salt 19117, Jordan
| | - Khaled M. Khleifat
- Department of Medical Laboratory Sciences, Faculty of Science, Mutah University, Al-Karak 61710, Jordan
| | - Ali Al-Samydai
- Department of Pharmaceutical and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Amman 11814, Jordan
| | - Belal O. Al-Najjar
- Department of Pharmaceutical and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Amman 11814, Jordan
| | - Fadi G. Saqallah
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan
| | - Yaseen T. Al Qaisi
- Department of Biological Sciences, Faculty of Science, Mutah University, Al-Karak 61710, Jordan
| | - Ahmad Z. Alsarayreh
- Department of Biological Sciences, Faculty of Science, Mutah University, Al-Karak 61710, Jordan
| | - Dana A. Alqudah
- Department of Pharmaceutics and Technology, Cell Therapy Center, The University of Jordan, Amman 11942, Jordan
| | - Abdulfattah S. Fararjeh
- Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Balqa Applied University, Al-Salt 19117, Jordan
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Wang YB, Salameen H, Hu YY, Zhou SJ, Gong JH. LncRNA DERCNC in Hepatocellular Carcinoma with Cirrhosis Aggravates Tumor Proliferation by Targeting SOX9. Curr Cancer Drug Targets 2025; 25:665-679. [PMID: 39041258 DOI: 10.2174/0115680096310229240626102449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 05/04/2024] [Accepted: 05/20/2024] [Indexed: 07/24/2024]
Abstract
PURPOSE This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). METHODS A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both in vitro and in vivo experiments. RESULTS The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter. CONCLUSION In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.
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Affiliation(s)
- Yun-Bing Wang
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Haitham Salameen
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Yi-Yu Hu
- The Second Clinical College, Chongqing Medical University, Chongqing, 400016, China
| | - Shi-Ji Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Jun-Hua Gong
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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Liu Y, Li Y, Chen L, Zha W, Zhang J, Wang K, Hao C, Gan J. Construction of an Oxidative Stress Risk Model to Analyze the Correlation Between Liver Cancer and Tumor Immunity. Curr Cancer Drug Targets 2025; 25:49-63. [PMID: 38375834 DOI: 10.2174/0115680096284532231220061048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/11/2023] [Accepted: 11/17/2023] [Indexed: 02/21/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Despite advancements in immunotherapy, the prognosis for patients with HCC continues to be poor. As oxidative stress plays a significant role in the onset and progression of various diseases, including metabolism-related HCC, comprehending its mechanism in HCC is critical for effective diagnosis and treatment. METHODS This study utilized the TCGA dataset and a collection of oxidative stress genes to identify the expression of oxidative stress-related genes in HCC and their association with overall survival using diverse bioinformatics methods. A novel prognostic risk model was developed, and the TCGA cohort was divided into high-risk and low-risk groups based on each tumor sample's risk score. Levels of immune cell infiltration and the expression of immune checkpoint-related genes in different risk subgroups were analyzed to investigate the potential link between tumor immunity and oxidative stress-related features. The expression of model genes in actual samples was validated through immunohistochemistry, and their mRNA and protein expression levels were measured in cell cultures. RESULTS Four oxidative stress-related genes (EZH2, ANKZF1, G6PD, and HMOX1) were identified and utilized to create a predictive risk model for HCC patient overall survival, which was subsequently validated in an independent cohort. A correlation was found between the expression of these prognostic genes and the infiltration of tumor immune cells. Elevated expression of EZH2, ANKZF1, G6PD, and HMOX1 was observed in both HCC tissues and cell lines. CONCLUSION The combined assessment of EZH2, ANKZF1, G6PD, and HMOX1 gene expression can serve as an oxidative stress risk model for assessing HCC prognosis. Furthermore, there is a correlation between the expression of these risk model genes and tumor immunity.
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Affiliation(s)
- Ying Liu
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yufeng Li
- Hebei Key Laboratory of Molecular Oncology, Tangshan People's Hospital, Tangshan, Hebei, 063001, China
- Institute of Cancer Research, Tangshan People's Hospital, Tangshan, China
| | - Li Chen
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Weina Zha
- Department of Endocrine, TangShan GongRen Hospital, Tangshan, China
| | - Jing Zhang
- Department of Hepatobiliary Medicine, Tangshan People's Hospital, Tangshan, China
| | - Kun Wang
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chunhai Hao
- Department of Hepatobiliary Medicine, Tangshan People's Hospital, Tangshan, China
| | - Jianhe Gan
- Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, China
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Liang H, Xu Y, Sun S, Chen Y, Wang W, Hao Z. Based on network pharmacology, the mechanism of Dioscin in alleviating renal tubular epithelial cell injury induced by calcium oxalate crystals was explored. Urolithiasis 2024; 53:3. [PMID: 39666011 DOI: 10.1007/s00240-024-01673-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 11/23/2024] [Indexed: 12/13/2024]
Abstract
The commencement of kidney stone formation involves a crucial initial phase characterized by injury to renal tubular cells caused by calcium oxalate (CaOx). Dioscin (Dio) has been acknowledged for its potent anti-inflammation and anti-apoptotic properties; nevertheless, the impact and underlying Investigation into the molecular basis underlying the action of Dioscin in mitigating inflammation and apoptotic induced by exposure to calcium oxalate crystals in renal tissues remain unexplored. To comprehend the precise mechanism of Dioscin in the treatment of crystalline nephropathy, we conducted experiments utilizing a murine model of CaOx crystal deposition, induced by intraperitoneal administration of glyoxylate. An in vitro model was constructed using HK-2 cells exposed to calcium oxalate monohydrate (COM). To evaluate the effect of Dioscin on calcium oxalate crystal deposition by ROS assay, Western blotting, immunohistochemistry, Periodic Acid-Schiff staining (PAS) staining, hematoxylin-eosin (H&E) staining. Using network pharmacology and molecular docking methods, we explored the molecular mechanism of Dioscin in the treatment of CaOx-induced renal tubular epithelial cell injury. Subsequently, we conducted experiments to verify our findings. We observed a significant protective effect of Dioscin treatment against kidney oxidative stress and inflammation induced by CaOx. Then we predicted through network pharmacology that Dioscin exerts its anti-apoptotic effect through the NF-kappa B signaling pathway. Then we verified in vitro and in vivo that administration of Dioscin can alleviate the elevation of TLR4 and activation of the NF-kappa B signaling pathway induced by calcium oxalate, as well as attenuate renal apoptosis. Instead, the beneficial impact of this protection of Dioscin was reversed after overexpression of the TLR4. Dioscin has the potential to alleviate the activation of the NF-kappa B signaling pathway through TLR4, thereby exerting anti-inflammatory and anti-apoptotic effects. This study provides new ideas for the prevention and treatment of kidney stones.
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Affiliation(s)
- Hu Liang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Urology, Anhui Medical University, Hefei, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China
| | - Yuexian Xu
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Urology, Anhui Medical University, Hefei, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China
| | - Shuai Sun
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Institute of Urology, Anhui Medical University, Hefei, China
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China
| | - Yang Chen
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- Institute of Urology, Anhui Medical University, Hefei, China.
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China.
| | - Wei Wang
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- Institute of Urology, Anhui Medical University, Hefei, China.
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China.
| | - Zongyao Hao
- Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- Institute of Urology, Anhui Medical University, Hefei, China.
- Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China.
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Bai Y, Liu F, Luo S, Wan Y, Zhang L, Wu X, Chen Q, Xie Y, Guo P. Experimental study on H 2O 2 activation of HSC-T6 and hepatic fibrosis in cholestatic mice by "Yajieshaba". JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118712. [PMID: 39173724 DOI: 10.1016/j.jep.2024.118712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/16/2024] [Accepted: 08/17/2024] [Indexed: 08/24/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Yajieshaba (YJSB), approved by the Yunnan Provincial Food and Drug Administration in 2008, are known for their anti-inflammatory, antiviral, and pro-apoptotic properties, effectively treating Hepatic fibrosis (HF). However, its mechanism of action remains unclear. AIM OF THE STUDY The objective of this investigation is to explore how YJSB influences the TGF-β1/Smad signaling pathway as a strategy for reducing HF. METHODS The establishment of a HF model in mice involved ligation of the common bile duct, followed by administration of YJSB. Body and liver weights were measured, and the liver index calculated. Serum levels of ALT, AST, ALP, TBA, and TBIL were assessed using colorimetric methods. Additionally, liver homogenates were analyzed for PIIINP, Col-IV, LN, HA, and Hyp, as well as TGF-β1 activity, using ELISA. Histological analyses of liver sections, stained with H&E, Ag, and Masson's trichrome, were performed to examine inflammation and the accumulation of collagen and reticular fibers. These studies aimed to elucidate the pharmacodynamic effects of YJSB on HF in mice with bile duct obstruction. The target pathways of YJSB were preliminarily identified through immunofluorescence detection of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, P-Smad3C, and Smad4 proteins. In vitro experiments included the induction of hepatic stellate cell (HSC-T6) activation by H2O2. A cell injury model was established for HSC-T6, and the CCK-8 assay was used to determine the optimal YJSB concentration and treatment duration. After pirfenidone (PFD) administration, which inhibits the TGF-β1/Smad pathway, the effects of YJSB on HSC-T6 cell proliferation were observed. ELISA assays quantified Col-III, α-SMA, and Col-I in cell lysates to assess YJSB's impact on collagen synthesis in HSC-T6 cells. Western blot analysis was performed to assess the protein levels within the TGF-β1/Smad signaling cascade. RESULTS In the HF mouse model, administration of YJSB notably augmented the body weight and reduced the liver index. Concurrently, there was an elevation in serum concentrations of ALP, AST, ALT, TBA, and TBIL. Similarly, in the liver homogenates of HF mice, increases were observed in the levels of HA, PIIINP, Col-IV, LN, Hyp, and TGF-β1. Histological assessments using H&E, Ag, and Masson stains indicated a substantial diminution in liver tissue damage. Through immunofluorescence analysis, it was discerned that YJSB modulated the expression of TGF-β1, P-Smad2L, P-Smad2C, and P-Smad3L downwards, while elevating P-Smad3C and Smad4 protein expressions. Additional investigations revealed a significant reduction in α-SMA, Col-I, and Col-III levels in cell culture fluids, suggesting a decrease in collagen synthesis and a protective role against cellular damage. Western blot analyses demonstrated that the TGF-β1/Smad pathway inhibitor, PFD, acted in synergy with YJSB, enhancing its regulatory effects on this pathway, decreasing levels of TGF-β1, P-Smad2L, P-Smad2C, P-Smad3L, and promoting the expression of P-Smad3C. CONCLUSIONS YJSB demonstrates a pharmacodynamic effect against HF, enhancing liver functionality and effectively mitigating the damage associated with bile duct obstruction. The proposed action mechanism of YJSB involves modulation of the TGF-β1/Smad signaling pathway. Research indicates that YJSB might play a role in suppressing the movement, programmed cell death, and activation of HSC-T6, potentially decelerating the advancement of hepatic fibrosis.
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Affiliation(s)
- Yuanmei Bai
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Feifan Liu
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Shifang Luo
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Yan Wan
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Linao Zhang
- College of Chinese Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Xue Wu
- College of Chinese Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China
| | - Qinghua Chen
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China.
| | - Yuhuan Xie
- College of Basic Medical Sciences, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China.
| | - Peixin Guo
- College of Ethnic Medicine, Yunnan University of Chinese Medicine, Yunnan, Kunming, 650500, China.
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Apaza-Ticona L, Beltrán M, Moraga E, Cossio D, Bermejo P, Guerra JA, Alcamí J, Bedoya LM. Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118613. [PMID: 39047879 DOI: 10.1016/j.jep.2024.118613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/10/2024] [Accepted: 07/21/2024] [Indexed: 07/27/2024]
Abstract
ETHNOPHARMACOLOGY RELEVANCE Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases. AIM OF THE STUDY The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity. MATERIAL AND METHODS Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids. RESULTS n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription. CONCLUSIONS n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.
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Affiliation(s)
- Luis Apaza-Ticona
- Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Complutense University of Madrid, Plza. Ramón y Cajal s/n, 28040, Madrid, Spain.
| | - Manuela Beltrán
- AIDS Immunopathology Department, National Centre of Microbiology, Carlos III Health Institute, Ctra. Pozuelo Km. 2, 28224, Madrid, Spain.
| | - Elisa Moraga
- HIV Unit, Hospital Clínic-IDIBAPS, University of Barcelona, c/ Rosselló, 149-153, 08036, Barcelona, Spain.
| | - David Cossio
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plza. Ramón y Cajal s/n, 28040, Madrid, Spain.
| | - Paulina Bermejo
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plza. Ramón y Cajal s/n, 28040, Madrid, Spain.
| | - José A Guerra
- Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plza. Ramón y Cajal s/n, 28040, Madrid, Spain.
| | - José Alcamí
- AIDS Immunopathology Department, National Centre of Microbiology, Carlos III Health Institute, Ctra. Pozuelo Km. 2, 28224, Madrid, Spain.
| | - Luis M Bedoya
- AIDS Immunopathology Department, National Centre of Microbiology, Carlos III Health Institute, Ctra. Pozuelo Km. 2, 28224, Madrid, Spain; Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid, Plza. Ramón y Cajal s/n, 28040, Madrid, Spain.
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Li H, Zeng X, Sun D, Qi X, Li D, Wang W, Lin Y. Albiflorin Alleviates Severe Acute Pancreatitis-Associated Liver Injury by Inactivating P38MAPK/NF-κB Signaling Pathway. Biochem Genet 2024; 62:4987-5003. [PMID: 38381358 DOI: 10.1007/s10528-024-10686-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 01/03/2024] [Indexed: 02/22/2024]
Abstract
Albiflorin (Alb) is a monoterpenoid component that is commonly found in Paeonia lactiflora Pall. or Paeonia veitchii Lynch. It is known for its impressive anti-oxidant and anti-inflammatory properties. However, the effect of Alb on severe acute pancreatitis (SAP)-associated liver injury has not been fully understood. To investigate this, we conducted a study using a rat model of SAP induced by administering two intraperitoneal injections of 20% L-arginine (3.3 g/kg) over a period of 2 h. Subsequently, the SAP-induced rats were randomly assigned into different groups with the treatment of gradient doses of Alb (5, 10, and 20 mg/kg), with the normal saline as the sham group. The pathological changes in rat livers were evaluated through hematoxylin-eosin staining. Furthermore, the levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using specific enzyme-linked immunosorbent assay kits. Moreover, the serum levels of inflammatory factors, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, were quantified. Finally, immunohistochemical and Western blot analyses were conducted to determine phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and mitogen-associated protein kianse (MAPK) p38 in the liver tissues. TNF-α stimulated liver cells were used as a cell model to further confirm the involvement of NF-κB and p38 in the effect of Alb. Our study revealed that Alb effectively mitigated the hepatic pathological damage in a dose-dependent manner and reduced the levels of indicators associated with hepatic malfunction (AMY, AST, and ALT) in rats with SAP-induced liver injury. Additionally, Alb demonstrated its ability to suppress inflammation and oxidative stress markers in the liver tissues. Alb exerted dose-dependent inhibitory effects by modulating the P38MAPK/NF-κB signaling pathway. Overall, our findings strongly support the hepatoprotective effect of Alb in rats with SAP-induced liver injury, suggesting that Alb protects against SAP-induced liver injury through the suppression of inflammation and oxidative stress via the P38MAPK/NF-κB signaling pathway.
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Affiliation(s)
- Haitao Li
- Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China
| | - Xiangpeng Zeng
- Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China
| | - Dongjie Sun
- Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China
| | - Xingfeng Qi
- Department of Pathology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China
| | - Dazhou Li
- Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China
| | - Wen Wang
- Department of Pathology, Fuzong Clinical Medical College of Fujian Medical University/The 900th Hospital of the Joint Logistics Support Force Fuzhou, No. 156, West Second Ring Road, Fuzhou City, 350025, Fujian, People's Republic of China.
| | - Yan Lin
- Department of Gastroenterology, Fuzhou Second Hospital Affiliated to Xiamen University, No. 47 Shangjidi Road, Cangshan District, Fuzhou City, 350007, Fujian, People's Republic of China.
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Yuen GKW, Lin S, Dong TTX, Tsim KWK. Sophoricoside, a genistein glycoside from Fructus Sophorae, promotes hair growth via activation of M4 muscarinic AChR in dermal papilla cells. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118585. [PMID: 39019417 DOI: 10.1016/j.jep.2024.118585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/08/2024] [Accepted: 07/14/2024] [Indexed: 07/19/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Alopecia, or hair loss, refers to ongoing decline of mature hair on the scalp or any other region of the body. Fructus Sophorae, a fruit from Sophora japonica L., contains various phytochemicals, e.g., sophoricoside, that exhibit a broad range of pharmacological effects. The potential functions of herbal extracts deriving from Fructus Sophorae and/or its major phytochemical, sophoricoside, in treating alopecia are probed here. AIM OF STUDY The objective was to determine the ability of Fructus Sophorae extract and sophoricoside in promoting hair growth and it signalling mechanism. METHODS Molecular docking studies were conducted to measure the binding affinities between sophoricoside and M4 mAChR in the allosteric binding site. The mechanism of Fructus Sophorae and sophoricoside in activating the signalling involving Wnt/β-catenin and muscarinic AChR was evaluated by using immortalized human dermal papilla cell line (DPC), as well as their roles in promoting hair growth. The activity of pTOPflash-luciferase in transfected DPCs was used to examine the transcriptional regulation of Wnt/β-catenin-mediated genes. RT-PCR was applied to quantify mRNA expressions of the biomarkers in DPCs responsible for hair growth. The phosphorylated protein levels of Wnt/β-catenin and PI3K/AKT in DPC were revealed by using Western blot analysis. The culture of ex vivo mouse vibrissae hair follicle was used to evaluate the hair growth after the treatments. RESULTS The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/β-catenin signalling. The result of molecular docking showed a high binding affinity between sophoricoside and M4 mAChR. The effect of sophoricoside was blocked by specific inhibitor of M4 mAChR, but not by other inhibitors of mAChRs. Sophoricoside promoted hair growth in cultured ex vivo mouse vibrissae hair follicle by acting through M4 mAChR. CONCLUSION The ethanol extract of Fructus Sophorae and sophoricoside activated Wnt/β-catenin signalling via activation of M4 mAChR. The results suggested beneficial functions of Fructus Sophorae and sophoricoside as a potential candidate in treating alopecia.
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Affiliation(s)
- Gary Ka-Wing Yuen
- Division of Life Science, Centre for Chinese Medicine, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
| | - Shengying Lin
- Division of Life Science, Centre for Chinese Medicine, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
| | - Tina Ting-Xia Dong
- Division of Life Science, Centre for Chinese Medicine, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
| | - Karl Wah-Keung Tsim
- Division of Life Science, Centre for Chinese Medicine, and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, 518057, China.
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Tian CB, Qin ML, Qian YL, Qin SS, Shi ZQ, Zhao YL, Luo XD. Liver injury protection of Artemisia stechmanniana besser through PI3K/AKT pathway. JOURNAL OF ETHNOPHARMACOLOGY 2024; 334:118590. [PMID: 39029542 DOI: 10.1016/j.jep.2024.118590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 07/21/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.
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Affiliation(s)
- Cai-Bo Tian
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China
| | - Ma-Long Qin
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China
| | - Yan-Ling Qian
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China
| | - Shi-Shi Qin
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China
| | - Zhuo-Qi Shi
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China
| | - Yun-Li Zhao
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China.
| | - Xiao-Dong Luo
- Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, PR China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China.
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Zhang S, Hou B, Xu A, Wen Y, Zhu X, Cai W, Han Z, Chen J, Nhamdriel T, Mi M, Qiu L, Sun H. Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization. JOURNAL OF ETHNOPHARMACOLOGY 2024; 332:118377. [PMID: 38782307 DOI: 10.1016/j.jep.2024.118377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/10/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. AIM OF THE STUDY This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. MATERIALS AND METHODS Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthritic(CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. RESULTS Metabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-κB, and STAT3 through hydrogen bonds, C-H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. CONCLUSION GLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1β signaling pathway and reduction in M1 macrophage polarization.
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Affiliation(s)
- Shijie Zhang
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Bao Hou
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Anjing Xu
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Yuanyuan Wen
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Xuexue Zhu
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Weiwei Cai
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China
| | - Zhijun Han
- Department of Clinical Research Center, Jiangnan University Medical Center, Wuxi, 214001, Jiangsu Province, China
| | - Jing Chen
- Department of Basic Medicine, Tibet University of Medicine, 850000, Lhasa, China
| | - Tsedien Nhamdriel
- Department of Basic Medicine, Tibet University of Medicine, 850000, Lhasa, China
| | - Ma Mi
- Department of Basic Medicine, Tibet University of Medicine, 850000, Lhasa, China.
| | - Liying Qiu
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China.
| | - Haijian Sun
- Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.
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12
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Nian Q, Liu R, Zeng J. Unraveling the pathogenesis of myelosuppression and therapeutic potential of natural products. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 132:155810. [PMID: 38905848 DOI: 10.1016/j.phymed.2024.155810] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/21/2024] [Accepted: 06/06/2024] [Indexed: 06/23/2024]
Abstract
BACKGROUND Myelosuppression is a serious and common complication of radiotherapy and chemotherapy in cancer patients and is characterized by a reduction of peripheral blood cells. This condition not only compromises the efficacy of treatment but also increases the risk of patient death. Natural products are emerging as promising adjuvant therapies due to their antioxidant properties, ability to modulate immune responses, and capacity to stimulate haematopoietic stem cell proliferation. These therapies demonstrate significant potential in ameliorating myelosuppression. METHODS A systematic review of the literature was performed utilizing the search terms "natural products," "traditional Chinese medicine," and "myelosuppression" across prominent databases, including Google Scholar, PubMed, and Web of Science. All pertinent literature was meticulously analysed and summarized. The objective of this study was to perform a pertinent analysis to elucidate the mechanisms underlying myelosuppression and to categorize and synthesize information on natural products and traditional Chinese medicines employed for the therapeutic management of myelosuppression. RESULTS Myelosuppression resulting from drug and radiation exposure, viral infections, and exosomes is characterized by multiple underlying mechanisms involving immune factors, target genes, and the activation of diverse signalling pathways, including the (TGF-β)/Smad pathway. Recently, traditional Chinese medicine monomers and compounds, including more than twenty natural products, such as Astragalus and Angelica, have shown promising potential as therapeutics for ameliorating myelosuppression. These natural products exert their effects by modulating haematopoietic stem cells, immune factors, and critical signalling pathways. CONCLUSIONS Understanding the various mechanisms of myelosuppression facilitates the exploration of natural product therapies and biological target identification for evaluating herbal medicine efficacy. This study aimed to establish a foundation for the clinical application of natural products and provide methodologies and technical support for exploring additional treatments for myelosuppression.
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Affiliation(s)
- Qing Nian
- Department of Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
| | - Rongxing Liu
- Department of Pharmacy, The Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Jinhao Zeng
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Ren Y, Sun Y, Liao YY, Wang S, Liu Q, Duan CY, Sun L, Li XY, Yuan JL. Mechanisms of action and applications of Polygonatum sibiricum polysaccharide at the intestinal mucosa barrier: a review. Front Pharmacol 2024; 15:1421607. [PMID: 39224782 PMCID: PMC11366640 DOI: 10.3389/fphar.2024.1421607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 08/01/2024] [Indexed: 09/04/2024] Open
Abstract
As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer's disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.
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Affiliation(s)
- Yu Ren
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi Sun
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Yu-Ying Liao
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Si Wang
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
- First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Qian Liu
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Chun-Yan Duan
- College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Lan Sun
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Xiao-Ya Li
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
| | - Jia-Li Yuan
- Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Diseasein Prevention and Treatment, School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, China
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Gong XX, Cao LH, Ni HX, Zang ZY, Chang H. Chinese herbal medicine for the treatment of diabetic nephropathy: From clinical evidence to potential mechanisms. JOURNAL OF ETHNOPHARMACOLOGY 2024; 330:118179. [PMID: 38636575 DOI: 10.1016/j.jep.2024.118179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 03/28/2024] [Accepted: 04/08/2024] [Indexed: 04/20/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetic nephropathy (DN) is a typical chronic microvascular complication of diabetes, characterized by proteinuria and a gradual decline in renal function. At present, there are limited clinical interventions aimed at preventing the progression of DN to end-stage renal disease (ESRD). However, Chinese herbal medicine presents a distinct therapeutic approach that can be effectively combined with conventional Western medicine treatments to safeguard renal function. This combination holds considerable practical implications for the treatment of DN. AIM OF THE STUDY This review covers commonly used Chinese herbal remedies and decoctions applicable to various types of DN, and we summarize the role played by their active ingredients in the treatment of DN and their mechanisms, which includes how they might improve inflammation and metabolic abnormalities to provide new ideas to cope with the development of DN. MATERIALS AND METHODS With the keywords "diabetic nephropathy," "Chinese herbal medicine," "clinical effectiveness," and "bioactive components," we conducted an extensive literature search of several databases, including PubMed, Web of Science, CNKI, and Wanfang database, to discover studies on herbal formulas that were effective in slowing the progression of DN. The names of the plants covered in the review have been checked at MPNS (http://mpns.kew.org). RESULTS This review demonstrates the superior total clinical effective rate of combining Chinese herbal medicines with Western medicines over the use of Western medicines alone, as evidenced by summarizing the results of several clinical trials. Furthermore, the review highlights the nephroprotective effects of seven frequently used herbs exerting beneficial effects such as podocyte repair, anti-fibrosis of renal tissues, and regulation of glucose and lipid metabolism through multiple signaling pathways in the treatment of DN. CONCLUSIONS The potential of herbs in treating DN is evident from their excellent effectiveness and the ability of different herbs to target various symptoms of the condition. However, limitations arise from the deficiencies in interfacing with objective bioindicators, which hinder the integration of herbal therapies into modern medical practice. Further research is warranted to address these limitations and enhance the compatibility of herbal therapies with contemporary medical standards.
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Affiliation(s)
- Xiao-Xiao Gong
- College of Food Science, Southwest University, Chongqing, 400715, China.
| | - Lin-Hai Cao
- College of Food Science, Southwest University, Chongqing, 400715, China.
| | - Hong-Xia Ni
- College of Food Science, Southwest University, Chongqing, 400715, China.
| | - Zi-Yan Zang
- College of Food Science, Southwest University, Chongqing, 400715, China.
| | - Hui Chang
- College of Food Science, Southwest University, Chongqing, 400715, China.
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Gao M, Zhu X, Gao X, Yang H, Li H, Du Y, Gao J, Chen Z, Dong H, Wang B, Zhang L. Kaempferol mitigates sepsis-induced acute lung injury by modulating the SphK1/S1P/S1PR1/MLC2 signaling pathway to restore the integrity of the pulmonary endothelial cell barrier. Chem Biol Interact 2024; 398:111085. [PMID: 38823539 DOI: 10.1016/j.cbi.2024.111085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/19/2024] [Accepted: 05/29/2024] [Indexed: 06/03/2024]
Abstract
Sepsis-induced acute lung injury (SALI) is the common complication of sepsis, resulting in high incidence and mortality rates. The primary pathogenesis of SALI is the interplay between acute inflammation and endothelial barrier damage. Studies have shown that kaempferol (KPF) has anti-sepsis properties. Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway's significance in acute lung damage and S1P receptor 1 (S1PR1) agonists potential in myosin light chain 2 (MLC2) phosphorylation are documented. Whether KPF can regulate the SphK1/S1P/S1PR1/MLC2 signaling pathway to protect the lung endothelial barrier remains unclear. This study investigates the KPF's therapeutic effects and molecular mechanisms in repairing endothelial cell barrier damage in both LPS-induced sepsis mice and human umbilical vein endothelial cells (HUVECs). KPF significantly reduced lung tissue damage and showed anti-inflammatory effects by decreasing IL-6 and TNF-α synthesis in the sepsis mice model. Further, KPF administration can reduce the high permeability of the LPS-induced endothelial cell barrier and alleviate lung endothelial cell barrier injury. Mechanistic studies showed that KPF pretreatment can suppress MLC2 hyperphosphorylation and decrease SphK1, S1P, and S1PR1 levels. The SphK1/S1P/S1PR1/MLC2 signaling pathway controls the downstream proteins linked to endothelial barrier damage, and the Western blot (WB) showed that KPF raised the protein levels. These proteins include zonula occludens (ZO)-1, vascular endothelial (VE)-cadherin and Occludin. The present work revealed that in mice exhibiting sepsis triggered by LPS, KPF strengthened the endothelial barrier and reduced the inflammatory response. The SphK1/S1P/S1PR1/MLC2 pathway's modulation is the mechanism underlying this impact.
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Affiliation(s)
- Meijuan Gao
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, 264003, PR China
| | - Xuan Zhu
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - XiaoJin Gao
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - Hui Yang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, 264003, PR China
| | - Haixia Li
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - Yuan Du
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - Jing Gao
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - Zhuoxi Chen
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, 264003, PR China
| | - Hanpeng Dong
- Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, School of Pharmacy, Yantai University, Yantai, 264005, PR China
| | - Binsheng Wang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, 264003, PR China.
| | - Leiming Zhang
- School of Traditional Chinese Medicine, Binzhou Medical University, Yantai, 264003, PR China.
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Hsieh HL, Yu MC, Chang YC, Wu YH, Huang KH, Tsai MM. Lonicera japonica Thunb. Ethanol Extract Exerts a Protective Effect on Normal Human Gastric Epithelial Cells by Modulating the Activity of Tumor-Necrosis-Factor-α-Induced Inflammatory Cyclooxygenase 2/Prostaglandin E2 and Matrix Metalloproteinase 9. Curr Issues Mol Biol 2024; 46:7303-7323. [PMID: 39057074 PMCID: PMC11276375 DOI: 10.3390/cimb46070433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through the activation of TNFR-ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.
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Affiliation(s)
- Hsi-Lung Hsieh
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
- Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Chemical Engineering, R&D Center of Biochemical Engineering Technology, Ming Chi University of Technology, New Taipei City 301, Taiwan
| | - Ming-Chin Yu
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Yu-Chia Chang
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
| | - Yi-Hsuan Wu
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
| | - Kuo-Hsiung Huang
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan;
- Department of Laboratory Medicine, Section of Clinical Serology and Immunology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Ming-Ming Tsai
- Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; (H.-L.H.); (Y.-C.C.); (Y.-H.W.)
- Department of General Surgery, New Taipei Municipal TuCheng Hospital, New Taipei 236, Taiwan;
- Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Department of Nursing, Division of Basic Medical Sciences, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan;
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Gong L, Wang W, Yu F, Deng Z, Luo N, Zhang X, Chen J, Peng J. Caffeic acid phenethyl ester derivative exerts remarkable anti-hepatocellular carcinoma effect, non-inferior to sorafenib, in vivo analysis. Sci Rep 2024; 14:14546. [PMID: 38914695 PMCID: PMC11196574 DOI: 10.1038/s41598-024-65496-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 06/20/2024] [Indexed: 06/26/2024] Open
Abstract
Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1' (CAPE 1') monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1', the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1' treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1' (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1' treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1' and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1' was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.
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Affiliation(s)
- Lei Gong
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Wenzhen Wang
- Department of Urology, Second Affiliated Hospital, Shandong University, Jinan, 250021, People's Republic of China
| | - Fei Yu
- Center of Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People's Republic of China
| | - Zenghua Deng
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Nan Luo
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Xinjing Zhang
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Jianfen Chen
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China
| | - Jirun Peng
- Department of Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China.
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Zhang H, Yin Y, Chen S, Qian P, Zou G, Liu Y, Yang J, Zhang H. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway. Open Life Sci 2024; 19:20220890. [PMID: 38911926 PMCID: PMC11193396 DOI: 10.1515/biol-2022-0890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 05/10/2024] [Accepted: 05/14/2024] [Indexed: 06/25/2024] Open
Abstract
Adverse cardiac mechanical remodeling is critical for the progression of heart failure following myocardial infarction (MI). We previously demonstrated the involvement of RIP3-mediated necroptosis in the loss of functional cardiomyocytes and cardiac dysfunction post-MI. Herein, we investigated the role of RIP3 in NOD-like receptor protein 3 (NLRP3)-mediated inflammation and evaluated the effects of RIP3 knockdown on myocardial mechanics and functional changes after MI. Our findings revealed that mice with MI for 4 weeks exhibited impaired left ventricular (LV) myocardial mechanics, as evidenced by a significant decrease in strain and strain rate in each segment of the LV wall during both systole and diastole. However, RIP3 knockdown ameliorated cardiac dysfunction by improving LV myocardial mechanics not only in the anterior wall but also in other remote nonischemic segments of the LV wall. Mechanistically, knockdown of RIP3 effectively inhibited the activation of the nuclear factor kappa-B (NF-κB)/NLRP3 pathway, reduced the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the heart tissues, and mitigated adverse cardiac remodeling following MI. These results suggest that downregulation of RIP3 holds promise for preventing myocardial inflammation and cardiac mechanical remodeling following MI by regulating the NF-κB/NLRP3 pathway.
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Affiliation(s)
- Han Zhang
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou510080, China
- Key Laboratory of Molecular Target & Clinical Pharmacology and The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, P.R. China
| | - Yuan Yin
- Department of Pharmacy, Affiliated Guangxi International Zhuang Medical Hospital, Guangxi University of Traditional Chinese Medicine, Guangxi, 530021, P.R. China
| | - Shan Chen
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou510080, China
| | - Peipei Qian
- Key Laboratory of Molecular Target & Clinical Pharmacology and The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, P.R. China
| | - Ganglin Zou
- Nanhai Mental Health Center, People's Hospital of Nanhai District, Foshan, 528200, P.R. China
| | - Yumei Liu
- Department of Pharmacology, Jiaying University, Meizhou, 514031, P.R. China
| | - Junying Yang
- Department of Stomatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou510080, China
| | - Haining Zhang
- Key Laboratory of Molecular Target & Clinical Pharmacology and The State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, P.R. China
- Department of Pharmacology, Guangzhou Medical University, Guangzhou, 511436, China
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Meng F, Li J, Dong K, Bai R, Liu Q, Lu S, Liu Y, Wu D, Jiang C, Li W. Juan-tong-yin potentially impacts endometriosis pathophysiology by enhancing autophagy of endometrial stromal cells via unfolded protein reaction-triggered endoplasmic reticulum stress. JOURNAL OF ETHNOPHARMACOLOGY 2024; 325:117859. [PMID: 38316218 DOI: 10.1016/j.jep.2024.117859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/01/2024] [Accepted: 02/02/2024] [Indexed: 02/07/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. AIM OF THE STUDY To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. MATERIALS AND METHODS The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). RESULTS In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. CONCLUSION JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs.
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Affiliation(s)
- Fengyun Meng
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Jing Li
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Kun Dong
- Department of Organ Transplantation, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Rui Bai
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Qiyu Liu
- Graduate School, Guangxi University of Chinese Medicine, Nanning, China
| | - Shijin Lu
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Ying Liu
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Dekun Wu
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Chen Jiang
- Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China
| | - Weihong Li
- Department of Nursing, Guangxi University of Chinese Medicine, Nanning, Guangxi Zhuang Autonomous Region, China.
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20
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Liu R, Yang C, Yang X, Yu J, Tang W. Network toxicology, molecular docking technology, and experimental verification revealed the mechanism of cantharidin-induced testicular injury in mice. Toxicol Appl Pharmacol 2024; 486:116921. [PMID: 38582374 DOI: 10.1016/j.taap.2024.116921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 03/22/2024] [Accepted: 04/02/2024] [Indexed: 04/08/2024]
Abstract
As a protein kinase inhibitor, cantharidin (CTD) exhibits antitumor activities. However, CTD is highly toxic, thereby limiting clinical applications. Moreover, relatively few studies have investigated CTD-induced reproductive toxicity, thus the underlying mechanism remains unclear. In this study, the toxic effects of CTD on mouse testis were confirmed in vivo and the potential mechanism was predicted by network toxicology (NT) and molecular docking technology. Proteins involved in the signaling pathways and core targets were verified. The results showed that different concentrations of CTD induced weight loss increased the testicular coefficient, and caused obvious pathological damage to testicular cells. The NT results showed that the main targets of CTD-induced testicular injury (TI) included AKT1, Caspase 3, Bcl-2, and Bax. The results of pathway enrichment analysis showed that CTD-induced TI was closely related to apoptosis and the PI3K/AKT and HIF-1 signaling pathways. Molecular docking methods confirmed high affinity between CTD and key targets. Western blot analysis showed that CTD inhibited expression of PI3K, AKT, and the anti-apoptotic protein Bcl-2, while promoting expression of the pro-apoptotic proteins Bax and Caspase 3. These results suggest that CTD-induced TI involves multiple targets and pathways, and the underlying mechanism was associated with inhibition of the apoptosis-related PI3K/AKT signaling pathway.
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Affiliation(s)
- Ruxia Liu
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Changfu Yang
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Xin Yang
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Jia Yu
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China
| | - Wenchao Tang
- Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
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21
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Liu H, Yue L, Li Y, Zheng T, Zhang W, Li C, Zhuang W, Fan L. Combination of Polygonatum Rhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON 3-induced mitochondrial damage and endoplasmic reticulum stress in A549 cells. ENVIRONMENTAL TOXICOLOGY 2024; 39:3172-3187. [PMID: 38348599 DOI: 10.1002/tox.24148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/15/2023] [Accepted: 12/29/2023] [Indexed: 04/17/2024]
Abstract
OBJECTIVE Scutellaria baicalensis (SB) and Polygonatum Rhizoma (PR), two traditional Chinese medicines, are both known to suppress cancer. However, the mechanism and effect of combined treatment of them for lung cancer are rarely known. Investigating the combined effect of SB and PR (hereafter referred to as SP) in potential mechanism of lung cancer is required. This study was to evaluate the inhibitory effects of SP on A549 cell growth and to explore the underlying molecular mechanisms. METHODS According to the theory of Chinese medicine and network pharmacology, in the in vivo experiment, a mouse model of carcinoma in situ was constructed, and lung carcinoma in situ tissues were collected for proteomics analysis, hematoxylin-eosin staining, and CK19 immunohistochemistry. In the in vitro experiment, lung cancer A549 cells at logarithmic growth stage were taken, and the inhibitory effect of SP on the proliferation of A549 cells was detected by CCK8 method. The expression of PON3 was detected by quantitative polymerase chain reaction and western blot. In addition, the effect of SP on the induction of apoptosis in A549 cells and the changes of membrane potential and reactive oxygen species (ROS) content were detected by flow cytometry. The changes of PON3 content in endoplasmic reticulum (ER) are observed by laser confocal microscopy, whereas the effects of SP on the expression of apoptosis-related proteins and ER stress-related proteins in A549 cells were examined by western blot. RESULT By searching the Traditional Chinese Medicines of Systems Pharmacology (TCMSP) (https://www.tcmspe.com/index.php) database and SymMap database, the respective target genes of PR and SB were mapped into protein network interactions, and using Venn diagrams to show 38 genes in common between PR and SB and lung cancer, SP was found to play a role in the treatment of lung cancer. In vivo experiments showed that in a lung carcinoma in situ model, lung tumor tissue was significantly lower in the SP group compared with the control group, and PON3 was shown to be downregulated by lung tissue proteomics analysis. The combination of SP was able to inhibit the proliferation of A549 cells in a concentration-dependent manner (p < .0001). The expression levels of apoptosis-related proteins and ER stress proteins were significantly increased and the expression levels of PON3 and anti-apoptosis-related proteins were decreased in A549 cells. At the same time, knockdown of PON3 could inhibit tumor cell proliferation (p < .0001). The combination of different concentrations of SP significantly induced apoptosis in A549 cells (p < .05; p < .0001), increased ROS content (p < .01), and damaged mitochondrial membrane potential of A549 cells (p < .05; p < .0001), and significantly increased the expression levels of apoptosis-related proteins and ER stress proteins in lung cancer A549 cells. CONCLUSION SP inhibits proliferation of lung cancer A549 cells by downregulating PON3-induced apoptosis in the mitochondrial and ER pathways.
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Affiliation(s)
- Haitao Liu
- Medical School, Anhui University of Science & Technology, Huainan, China
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Energy Metabolism and Health, Tongji University School of Medicine, Shanghai, China
| | - Liduo Yue
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yubin Li
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tiansheng Zheng
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Department of Integrated Traditional Chinese & Western Medicine, Shanghai Tenth People's, Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenjia Zhang
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Chaoqun Li
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Wenbin Zhuang
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Lihong Fan
- Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Institute of Energy Metabolism and Health, Tongji University School of Medicine, Shanghai, China
- Department of Integrated Traditional Chinese & Western Medicine, Shanghai Tenth People's, Hospital, Tongji University School of Medicine, Shanghai, China
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Rabie MA, Ghoneim AT, Fahmy MI, El-Yamany MF, Sayed RH. Activation of alpha-7 nicotinic acetylcholine receptor by tropisetron mitigates 3-nitropropionic acid-induced Huntington's disease in rats: Role of PI3K/Akt and JAK2/NF-κB signaling pathways. Chem Biol Interact 2024; 393:110957. [PMID: 38513929 DOI: 10.1016/j.cbi.2024.110957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/09/2024] [Accepted: 03/13/2024] [Indexed: 03/23/2024]
Abstract
Huntington's disease (HD) is an inheritable autosomal-dominant disorder that targets mainly the striatum. 3-Nitropropionic acid (3-NP) induces obvious deleterious behavioral, neurochemical, and histological effects similar to the symptoms of HD. Our study aimed to examine the neuroprotective activity of tropisetron, an alpha-7 neuronal nicotinic acetylcholine receptor (α-7nAChR) agonist, against neurotoxic events associated with 3-NP-induced HD in rats. Forty-eight rats were randomly allocated into four groups. Group I received normal saline, while Groups II, III and IV received 3-NP for 2 weeks. In addition, Group III and IV were treated with tropisetron 1 h after 3-NP administration. Meanwhile, Group IV received methyllycaconitine (MLA), an α-7nAChR antagonist, 30 min before tropisetron administration. Treatment with tropisetron improved motor deficits as confirmed by the behavioral tests and restored normal histopathological features of the striatum. Moreover, tropisetron showed an anti-oxidant activity via increasing the activities of SDH and HO-1 as well as Nrf2 expression along with reducing MDA level. Tropisetron also markedly upregulated the protein expression of p-PI3K and p-Akt which in turn hampered JAK2/NF-κB inflammatory cascade. In addition, tropisetron showed an anti-apoptotic activity through boosting the expression of Bcl-2 and reducing Bax expression and caspase-3 level. Interestingly, all the aforementioned effects of tropisetron were blocked by pre-administration of MLA, which confirms that such neuroprotective effects are mediated via activating of α-7nAChR. In conclusion, tropisetron showed a neuroprotective activity against 3-NP-induced HD via activating PI3K/Akt signaling and suppressing JAK2/NF-κB inflammatory axis. Thus, repositioning of tropisetron could represent a promising therapeutic strategy in management of HD.
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Affiliation(s)
- Mostafa A Rabie
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt.
| | - Ahmed T Ghoneim
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Mohamed I Fahmy
- Department of Pharmacology and Toxicology, College of Pharmaceutical sciences and drug manufacturing, Misr University for Science and Technology (MUST), 12585, Giza, Egypt
| | - Mohammed F El-Yamany
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt
| | - Rabab H Sayed
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt; School of Pharmacy, Newgiza University, Giza, Egypt
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Wei X, Wang D, Liu J, Zhu Q, Xu Z, Niu J, Xu W. Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments. Nutrients 2024; 16:1167. [PMID: 38674858 PMCID: PMC11054788 DOI: 10.3390/nu16081167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/07/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, and in vitro experiments were integrated to verify the antidepressant active ingredients in PR and their mechanisms. A total of seven compounds in PR were found to be associated with 45 targets of depression. Preliminarily, DFV docking with cyclooxygenase 2 (COX2) showed good affinity. In vitro, DFV inhibited lipopolysaccharide (LPS)-induced inflammation of BV-2 cells, reversed amoeba-like morphological changes, and increased mitochondrial membrane potential. DFV reversed the malondialdehyde (MDA) overexpression and superoxide dismutase (SOD) expression inhibition in LPS-induced BV-2 cells and decreased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA expression levels in a dose-dependent manner. DFV inhibited both mRNA and protein expression levels of COX2 induced by LPS, and the activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and caspase1 was suppressed, thus exerting an antidepressant effect. This study proves that DFV may be an important component basis for PR to play an antidepressant role.
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Affiliation(s)
- Xin Wei
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
| | - Dan Wang
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
| | - Jiajia Liu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
| | - Qizhi Zhu
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
| | - Ziming Xu
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
| | - Jinzhe Niu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China
| | - Weiping Xu
- Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
- Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei 230001, China
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24
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Li C, Yang J, Chu L, Tian J, Xiao J, Huang Y, Wang Q, Guo B, Huang L, Hu Y, Luo Y. The function of Bazhen decoction in rescuing progeroid cell senescence via facilitating G-quadruplex resolving and telomere elongation. JOURNAL OF ETHNOPHARMACOLOGY 2024; 323:117694. [PMID: 38163559 DOI: 10.1016/j.jep.2023.117694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/20/2023] [Accepted: 12/29/2023] [Indexed: 01/03/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for treatment of aging related diseases. However, due to the complexity of the components, the pharmacological mechanism of Bazhen decoction is still limited. AIM OF THE STUDY In this study, with the aim of helping the clinical precision medicine of TCM, we try out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription: Bazhen decoction. We identify the pharmacological mechanism of Bazhen decoction in telomere elongation as revealed by systematic analysis. MATERIALS AND METHODS By RNA sequencing and transcriptome analysis of Bazhen decoction treated wild type cells, we reveal the transcriptome profile induced by Bazhen decoction. We utilized the cells derived from Werner syndrome (WS) mice, which is known to be dysfunctional in telomere elongation due to the deficiency of DNA helicase Wrn. By Western blot, qPCR, Immunofluorescence, flow cytometry, telomere FISH, and SA-β-Gal staining, we verify the transcriptome data and confirm the pharmacological function of Bazhen decoction and its drug containing serum in telomere elongation and reversing progeroid cell senescence. RESULTS We reveal that Bazhen decoction may systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We find that Bazhen decoction and its drug containing serum could up-regulate multiple DNA helicases and telomere regulating proteins. The increased DNA helicases promote the resolving of G-quadruplex (G4) structures, and facilitate DNA replication and telomere elongation. These improvements also endow the cellular resistance to DNA damages induced by replication stress, and rescue the WS caused cellular senescence. CONCLUSIONS Together these data suggest that Bazhen decoction up-regulate the expression of DNA helicases, thus facilitate G4 resolving and telomere maintenance, which rescue the progeroid cellular senescence and contribute to its anti-aging properties. Our data reveal a new molecular mechanism of Bazhen decoction in anti-aging related diseases via elongating telomere, this may shed light in the application of Bazhen decoction in multiple degenerative diseases caused by telomere erosion.
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Affiliation(s)
- Chuanbiao Li
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Jun Yang
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Lili Chu
- Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Jie Tian
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Jinchao Xiao
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guizhou, China
| | - Yong Huang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guizhou, China
| | - Qianqian Wang
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Bing Guo
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China
| | - Liming Huang
- The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guizhou, China
| | - Ying Hu
- Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guizhou, China.
| | - Ying Luo
- Department of Pathophysiology, School of Basic Medicine, Guizhou Medical University, Guizhou, China.
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Xu F, Zhang H, Chen J, Zhan J, Liu P, Liu W, Qi S, Mu Y. Recent progress on the application of compound formulas of traditional Chinese medicine in clinical trials and basic research in vivo for chronic liver disease. JOURNAL OF ETHNOPHARMACOLOGY 2024; 321:117514. [PMID: 38042388 DOI: 10.1016/j.jep.2023.117514] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 12/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo, which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. AIM OF THE REVIEW This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. MATERIALS AND METHODS Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). RESULTS In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo, this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. CONCLUSION The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing.
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Affiliation(s)
- Feipeng Xu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China
| | - Hua Zhang
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China
| | - Jiamei Chen
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China
| | - Junyi Zhan
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China
| | - Ping Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China; Institute of Interdisciplinary Complex Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Wei Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China; Department of pharmacy, The SATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Shenglan Qi
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China; Department of pharmacy, The SATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Complex Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yongping Mu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, 201203, China.
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Chen D, Ren Y, Jin J, Liu S, Zhan X, Li X, Liang R, Ding Z. Pingchong Jiangni recipe through nerve growth factor/transient receptor potential vanilloid 1 signaling pathway to relieve pain in endometriosis model rats. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116940. [PMID: 37479067 DOI: 10.1016/j.jep.2023.116940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 07/17/2023] [Accepted: 07/19/2023] [Indexed: 07/23/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Pingchong Jiangni recipe (PJR) is often used in the treatment of endometriosis (EM). This formula has been clinically validated by the State Administration of Traditional Chinese Medicine Key Specialties Collaborative Group for its therapeutic efficacy. Recently, our research team also confirmed that PJR has a shrinking effect on ovarian chocolate cysts. Additionally, PJR was also found to have a shrinking effect on EM lesions; however, the mechanism by which this effect occurs remains unclear. AIM OF THE STUDY To explore the mechanisms by which PJR relieves pain in patients with EM. MATERIALS AND METHODS A rat model of EM was established by autologous transplantation. PJR (3.78 g/kg, 7.56 g/kg, and 15.12 g/kg) was orally administered for 21 days. The rat grimace scale (RGS) score and paw withdrawal threshold (PWT) were measured at a fixed time during the experiment. Hematoxylin and eosin staining was performed to observe histopathological changes in EM rats after administration, enzyme-linked immunosorbent assay to evaluate the plasma expression of tumor necrosis factor-α (TNF-α) and nerve growth factor (NGF), and immunohistochemistry and western blotting to identify differences in the expression of pain-related factors in EM rats. RESULTS The medium-dose group of PJR (7.56 g/kg) had the best effect on relieving pain in EM rats by reducing RGS, increasing PWT, reducing the ectopic endometrium, improving the cellular structure of the lesion, and reducing TNF-α and NGF levels. However, PJR significantly decreased the expression of transient receptor potential vanilloid 1 (TRPV1), phosphorylated TRPV1 (p-TRPV1), protein kinase C (PKC), and NGF. CONCLUSION The mechanism by which PJR relieves EM pain may be through the downregulation of NGF, PKC, and TRPV1 expression.
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Affiliation(s)
- Danni Chen
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Yunying Ren
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Jing Jin
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Shuzhen Liu
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xiaoxuan Zhan
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Xin Li
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Ruining Liang
- Second Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
| | - Zhiling Ding
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi Province, China.
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Xu B, Liang J, Fu L, Wei J, Lin J. A Novel Oncogenic Role of Disulfidptosis-related Gene SLC7A11 in Anti-tumor Immunotherapy Response to Human Cancers. Curr Cancer Drug Targets 2024; 24:846-866. [PMID: 38303526 DOI: 10.2174/0115680096277818231229105732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 10/22/2023] [Accepted: 11/08/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND The protein Solute Carrier Family 7 Member 11 (SLC7A11) plays a pivotal role in cellular redox homeostasis by suppressing disulfidptosis, which restricts tumor growth. Yet, its relevance in prognosis, immunity, and cancer treatment efficacy is not well understood. METHODS We conducted a comprehensive analysis of the expression of SLC7A11 across 33 cancer types, employing datasets from public databases. Methods, such as Cox regression and survival analyses assessed its prognostic significance, while functional enrichment explored the biological processes tied to SLC7A11. The association between SLC7A11 expression, immune cell infiltration, and immune-related gene expression was also scrutinized. RESULTS Notably, SLC7A11 expression was more pronounced in cancerous compared to normal samples and correlated with higher tumor grades. Increased SLC7A11 expression was linked to poor outcomes, particularly in liver hepatocellular carcinoma (LIHC). This protein's expression also showcased significant relationships with diverse molecular and immune subtypes. Additionally, a prognostic nomogram was devised, integrating SLC7A11 expression and clinical variables. High SLC7A11 levels corresponded with cell growth and senescence pathways in various cancers and with lipid and cholesterol metabolism in LIHC. Furthermore, potential therapeutic compounds for LIHC with high SLC7A11 were identified. Real-time PCR (qPCR) and Western blot were conducted to explore the expression of SLC7A11 in tumor tissues and cancer cell lines. CONCLUSION In summation, this study emphasizes the prognostic and immunological importance of SLC7A11, spotlighting its potential as a therapeutic target in LIHC.
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Affiliation(s)
- Borui Xu
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Jiahua Liang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China
| | - Liangmin Fu
- Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Jinhuan Wei
- Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China
| | - Juan Lin
- Department of Pediatrics, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, People's Republic of China
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Delmondes GDA, Pereira Lopes MJ, Borges ADS, Bezerra DS, Silva JPD, Souto BS, Costa JGDS, Campos PEDS, Santana TID, Coutinho HDM, Barbosa-Filho JM, Alencar de Menezes IR, Bezerra Felipe CF, Kerntopf MR. Investigation of mechanisms of action involved in the antidepressant-like effect of Trans,trans-farnesol in mice. Chem Biol Interact 2023; 386:110791. [PMID: 37923004 DOI: 10.1016/j.cbi.2023.110791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 10/23/2023] [Accepted: 10/31/2023] [Indexed: 11/07/2023]
Abstract
This study aimed to investigate, through in vivo and biochemical methodologies, the effect of trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) acute administration, adopting different behavioral and neurochemical parameters associated with an acute induced-depression model in mice. The initial results showed that, the oral treatment with trans,trans-farnesol, at the dose of 100 mg/kg induced a possible antidepressant-like effect in animals subjected to forced swim test (FST) and reserpine-induced akinesia. In addition, it was observed that the compound in question has an effect size and properties similar to imipramine (prototype of tricyclic antidepressants), but devoid of proconvulsant adverse effect. In biochemical assays, the pretreatment with trans,trans-farnesol, at a dose of 100 mg/kg (p.o.), decreased the hippocampal concentration of thiobarbituric acid reactive substances (TBARS) and restored striatal levels of noradrenaline and serotonin in mice subjected to FST. Altogether, these results suggest that trans,trans-farnesol showed a significant antidepressant-like effect, which seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress and the modulation of noradrenaline and serotonin content in the central nervous system.
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Affiliation(s)
- Gyllyandeson de Araújo Delmondes
- Postgraduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil; Nursing Collegiate, Federal University of São Francisco Valley, Petrolina, PE, Brazil.
| | | | - Alex de Sousa Borges
- Postgraduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil
| | - Daniel Souza Bezerra
- Postgraduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil; Natural Products Pharmacology Laboratory, Regional University of Cariri, Crato, CE, Brazil
| | - Jairo Pessoa da Silva
- Nursing Collegiate, Federal University of São Francisco Valley, Petrolina, PE, Brazil
| | - Bruna Silva Souto
- Nursing Collegiate, Federal University of São Francisco Valley, Petrolina, PE, Brazil
| | | | | | | | | | | | | | | | - Marta Regina Kerntopf
- Postgraduate Program in Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil; Natural Products Pharmacology Laboratory, Regional University of Cariri, Crato, CE, Brazil
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Prasher P, Fatima R, Sharma M, Tynybekov B, Alshahrani AM, Ateşşahin DA, Sharifi-Rad J, Calina D. Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship. Chem Biol Interact 2023; 386:110747. [PMID: 37816447 DOI: 10.1016/j.cbi.2023.110747] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/22/2023] [Accepted: 09/22/2023] [Indexed: 10/12/2023]
Abstract
Lignans are plant-derived polyphenolic compounds with a plethora of biological applications. Also, regarded as phytoestrogens, the lignans offer a variety of health benefits of which the anti-cancer effects are the most attractive. Honokiol is a lignan isolated from various parts of trees belonging to the genus Magnolia. The bioactivity of honokiol is attributed to its characteristic physical properties, which include small size and the presence of two phenolic groups that may interact with proteins in cell membranes via hydrophobic interactions, aromatic pi orbital co-valency, and hydrogen bonding. The hydrophobicity of honokiol enables its rapid dissolution in lipids and the crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid. These factors contribute towards the high bioavailability of honokiol which further support its candidature in medicinal research. Therefore, the anticancer properties of honokiol are of particular interest as many of the contemporary anticancer drugs suffer from bioavailability drawbacks, which necessitates the identification and development of novel candidate molecules directed as anticancer chemotherapeutics. The antioncogenic profile of honokiol also arises from the regulation of various signalling pathways associated with oncogenesis, arresting of the cell cycle by regulation of cyclic proteins, upregulation of epithelial markers and downregulation of mesenchymal markers leading to the inhibition of epithelial-mesenchymal transition, and preventing the metastasis by restricting cell migration and invasion due to the downregulation of matrix-metalloproteinases. In this review, we discuss the anticancer properties of honokiol.
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Affiliation(s)
- Parteek Prasher
- Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, 248007, India.
| | - Rabab Fatima
- Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, 248007, India.
| | - Mousmee Sharma
- Department of Chemistry, Uttaranchal University, Arcadia Grant, Dehradun, 248007, India.
| | - Bekzat Tynybekov
- Al-Farabi Kazakh National University, Department of Biodiversity and Bioresources, Almaty, Kazakhstan.
| | - Asma M Alshahrani
- Department of Clinical Pharmacy, Faculty of Pharmacy, King Khalid University, Abha, Saudi Arabia.
| | - Dilek Arslan Ateşşahin
- Fırat University, Baskil Vocational School, Department of Plant and Animal Production, 23100, Elazıg, Turkey.
| | | | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
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30
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Wang L, Xie Y, Myrzagali S, Pu W, Liu E. Metal ions as effectual tools for cancer with traditional Chinese medicine. ACUPUNCTURE AND HERBAL MEDICINE 2023; 3:296-308. [DOI: 10.1097/hm9.0000000000000083] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Malignant tumor has become a major threat affecting human health, and is one of the main causes of human death. Recent studies have shown that many traditional Chinese medicines (TCM) have good anti-tumor activity, which may improve the therapeutic effect of routine treatment and quality of life with lower toxicity. However, the efficacy of TCM alone for the treatment of tumors is limited. Metal ions are essential substances for maintaining normal physiological activities. This article summarized the multiple mechanisms in which metal ions are involved in the prevention and treatment of tumors in TCM.
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Affiliation(s)
- Lei Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yingqiu Xie
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
| | - Sandugash Myrzagali
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
| | - Weiling Pu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Erwei Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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31
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Selvan TG, Gollapalli P, Kumar SHS, Ghate SD. Early diagnostic and prognostic biomarkers for gastric cancer: systems-level molecular basis of subsequent alterations in gastric mucosa from chronic atrophic gastritis to gastric cancer. J Genet Eng Biotechnol 2023; 21:86. [PMID: 37594635 PMCID: PMC10439097 DOI: 10.1186/s43141-023-00539-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 07/31/2023] [Indexed: 08/19/2023]
Abstract
PURPOSE It is important to comprehend how the molecular mechanisms shift when gastric cancer in its early stages (GC). We employed integrative bioinformatics approaches to locate various biological signalling pathways and molecular fingerprints to comprehend the pathophysiology of the GC. To facilitate the discovery of their possible biomarkers, a rapid diagnostic may be made, which leads to an improved diagnosis and improves the patient's prognosis. METHODS Through protein-protein interaction networks, functional differentially expressed genes (DEGs), and pathway enrichment studies, we examined the gene expression profiles of individuals with chronic atrophic gastritis and GC. RESULTS A total of 17 DEGs comprising 8 upregulated and 9 down-regulated genes were identified from the microarray dataset from biopsies with chronic atrophic gastritis and GC. These DEGs were primarily enriched for CDK regulation of DNA replication and mitotic M-M/G1 phase pathways, according to KEGG analysis (p > 0.05). We discovered two hub genes, MCM7 and CDC6, in the protein-protein interaction network we obtained for the 17 DEGs (expanded with increased maximum interaction with 110 nodes and 2103 edges). MCM7 was discovered to be up-regulated in GC tissues following confirmation using the GEPIA and Human Protein Atlas databases. CONCLUSION The elevated expression of MCM7 in both chronic atrophic gastritis and GC, as shown by our comprehensive investigation, suggests that this protein may serve as a promising biomarker for the early detection of GC.
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Affiliation(s)
- Tamizh G Selvan
- Central Research Laboratory, K S Hegde Medical Academy, Nitte (Deemed to Be University), Deralakatte, Mangalore, 575018, Karnataka, India
| | - Pavan Gollapalli
- Center for Bioinformatics, University Annexe, Nitte (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India.
| | - Santosh H S Kumar
- Department of Biotechnology, Jnana Sahyadri Campus, Kuvempu University, Shankaraghatta, 577451, Karnataka, India
| | - Sudeep D Ghate
- Center for Bioinformatics, University Annexe, Nitte (Deemed to be University), Deralakatte, Mangalore, 575018, Karnataka, India
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Cheng Y, Huang X, Li L, Liu L, Zhang C, Fan X, Xie Y, Zou Y, Geng Z, Huang C. Effects of Solid Fermentation on Polygonatum cyrtonema Polysaccharides: Isolation, Characterization and Bioactivities. Molecules 2023; 28:5498. [PMID: 37513370 PMCID: PMC10384955 DOI: 10.3390/molecules28145498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/09/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders.
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Affiliation(s)
- Yi Cheng
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Xueyuan Huang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Lixia Li
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Lu Liu
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Chunsheng Zhang
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Xiang Fan
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Yu Xie
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Yuanfeng Zou
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Zhe Geng
- Department of Physical Education, Chengdu University of Information Technology, Chengdu 611130, China
| | - Chao Huang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
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Zhang W, Huang Q, Kang Y, Li H, Tan G. Which Factors Influence Healthy Aging? A Lesson from the Longevity Village of Bama in China. Aging Dis 2023; 14:825-839. [PMID: 37191421 PMCID: PMC10187713 DOI: 10.14336/ad.2022.1108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 11/08/2022] [Indexed: 11/18/2022] Open
Abstract
A growing aging population is associated with increasing incidences of aging-related diseases and socioeconomic burdens. Hence, research into healthy longevity and aging is urgently needed. Longevity is an important phenomenon in healthy aging. The present review summarizes the characteristics of longevity in the elderly population in Bama, China, where the proportion of centenarians is 5.7-fold greater than the international standard. We examined the impact of genetic and environmental factors on longevity from multiple perspectives. We proposed that the phenomenon of longevity in this region is of high value for future investigations in healthy aging and aging-related disease and may provide guidance for fostering the establishment and maintenance of a healthy aging society.
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Affiliation(s)
- Wei Zhang
- Department of Human Anatomy, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning, Guangxi, China.
- China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China.
| | - Qingyun Huang
- Department of Human Anatomy, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning, Guangxi, China.
- China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China.
| | - Yongxin Kang
- Department of Human Anatomy, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, Nanning, Guangxi, China.
- China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China.
| | - Hao Li
- Department of Human Anatomy, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, Nanning, Guangxi, China.
- China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China.
| | - Guohe Tan
- Department of Human Anatomy, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science, Guangxi Health Commission Key Laboratory of Basic Research on Brain Function and Disease, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Nanning, Guangxi, China.
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, Nanning, Guangxi, China.
- China-ASEAN Research Center for Innovation and Development in Brain Science, Nanning, Guangxi, China.
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Chen X, Zheng M, Fei X, Ma X. Analysis of the efficacy of Dabuyin pill combined with gonadotropin-releasing hormone analogue in the treatment of central precocious puberty girls based on network pharmacology. Transl Pediatr 2023; 12:364-374. [PMID: 37035395 PMCID: PMC10080485 DOI: 10.21037/tp-23-111] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/23/2023] [Indexed: 04/11/2023] Open
Abstract
BACKGROUND Traditional Chinese medicine (TCM) believes that central precocious puberty (CPP) is affected by the imbalance of kidney Yin and Yang. Dabuyin pill is a recipe for nourishing Yin and lowering fire. The network pharmacology method was used to analyze the active components, action targets, and molecular pathways of Dabuyin pill in the treatment of CPP. METHODS The main chemical components of Dabuyin pill were obtained from the Integrative database of Traditional Chinese Medicine enhanced by Symptom Mapping (SymMap) database and Traditional Chinese Medicine Systems Pharmacology (TCMSP), and compound targets were retrieved from SymMap and the Encyclopedia of Traditional Chinese Medicine (ETCM). Disease targets were retrieved from the DisGeNET and Gene Expression Omnibus (GEO) databases, and the intersection of compound targets and disease targets was performed to obtain the prediction targets of Dabuyin pill acting on CPP. The key targets enriched by Database for Annotation, Visualization, and Integrated Discovery (DAVID) were then used for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS GO analysis showed that the biological functions of Dabuyin pill in the treatment of key targets of CPP mainly involved apoptosis, nitric oxide synthesis, estradiol response, angiogenesis, inflammation, and so on. KEGG pathway analysis was mainly enriched in the tumor necrosis factor (TNF) signaling pathway, phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, and apoptosis. Among them, the regulation effect of Dabuyin pill prescription on apoptosis may both act on TP53 and different signaling pathways of apoptosis, thus playing a synergistic role. CONCLUSIONS Dabuyin pill combined with GnRHa for the prevention and treatment of CPP in girls can effectively intervene CPP, and the effect of Dabuyin pill on sex hormones is one of its protective mechanisms against CPP.
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Affiliation(s)
- Xiaohong Chen
- Department of Pediatrics, Central Hospital of Haining, Haining, China
| | - Min Zheng
- Day Surgery Center, Children’s Hospital of Wuhan, Wuhan, China
| | - Xiaoling Fei
- Department of Pediatrics, Central Hospital of Haining, Haining, China
| | - Xiaohui Ma
- Department of Pediatrics, Central Hospital of Haining, Haining, China
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Luo D, Wang X, Luo X, Wu S. Low-dose of zeolitic imidazolate framework-8 nanoparticle cause energy metabolism disorder through lysosome-mitochondria dysfunction. Toxicology 2023; 489:153473. [PMID: 36870412 DOI: 10.1016/j.tox.2023.153473] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 02/25/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023]
Abstract
Understanding the underlying interaction between nanoparticle and organelles is conclusive to the nanotoxicology. According to existing literatures, lysosome is a crucial target of the nanoparticle carrier. Meanwhile, mitochondria could provide the essential energy for nanopaticles entering/exiting the cell. Based on the investigation of lysosome-mitochondria connection, we decoded the effects of low-dose ZIF-8 on energy metabolism, which are still largely obscure beforehand. In this research, low-dose ZIF-8 NPs were utilized to explore the effects on vascular endothelial cells, the first cells exposed to NPs during intravenous injection. Consequently, ZIF-8 could damage the energy metabolism, mainly manifested as mitochondrial fission, the decreased ATP production, and lysosomal dysfuction, which would subsequently affect the cell survival, proliferation and protein expression. This study highlights the fundamental understanding for exploring the regulation of nanoscale ZIF-8 in biological processes and its further application in biomedical field.
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Affiliation(s)
- Dan Luo
- Core Facilities of West China Hospital, Sichuan University, Chengdu, China
| | - Xiaojiao Wang
- Core Facilities of West China Hospital, Sichuan University, Chengdu, China
| | - Xin Luo
- Core Facilities of West China Hospital, Sichuan University, Chengdu, China
| | - Sisi Wu
- Core Facilities of West China Hospital, Sichuan University, Chengdu, China.
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Ahmad A, Makhmutova Z, Cao W, Majaz S, Amin A, Xie Y. Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach. Expert Rev Anti Infect Ther 2023; 21:317-327. [PMID: 36757420 DOI: 10.1080/14787210.2023.2179035] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
BACKGROUND Although androgen in gender disparity of COVID-19 has been implied, no direct link has been provided. RESEARCH DESIGN AND METHODS Here, we applied AlphaFold multimer, network and single cells database analyses to highlight specificity of Androgen receptor (AR) against spike receptor binding protein (RBD) of SARS-CoV-2. RESULTS LXXL motifs in spike RBD are essential for AR binding. RBD LXXA mutation complex with the AR depicting slightly reduced binding energy, as LXXLL motif usually mediates nuclear receptor binding to coregulators. Moreover, AR preferred to bind a LYRL motif in specificity and interaction interface, and showed reduced affinity against Omicron compared to other variants (alpha, beta, gamma, and delta). Importantly, RBD LYRL motif is a conserved antigenic epitope (9 residues) for T-cell response. Network analysis of AR-related genes against COVID-19 database showed T-cell signaling regulation, and CD8+ T-cell spatial location in AR+ single cells, which is consistent with the AR binding motif LYRL in epitope function. CONCLUSIONS We provided the potent mechanisms of AR binding to RBD linking to immune response and vaccination shift. AR could be an anti-infective therapy target for anti-Omicron new lineages.
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Affiliation(s)
- Ashfaq Ahmad
- Department of Bioinformatics, Hazara University, Mansehra, Pakistan
| | - Zhandaulet Makhmutova
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
| | - Wenwen Cao
- Respiratory Department, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China
| | - Sidra Majaz
- Department of Bioinformatics, Hazara University, Mansehra, Pakistan
| | - Amr Amin
- Biology Department, UAE University, Al Ain, UAE
| | - Yingqiu Xie
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan
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Yang D, Tan YM, Zhang Y, Song JK, Luo Y, Luo Y, Fei XY, Ru Y, Li B, Jiang JS, Kuai L. Sheng-ji Hua-yu ointment ameliorates cutaneous wound healing in diabetes via up-regulating CCN1. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:115954. [PMID: 36435409 DOI: 10.1016/j.jep.2022.115954] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/12/2022] [Accepted: 11/16/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Diabetic ulcers (DUs) are one of the most severe complications of diabetes, and efficacious therapeutic means are currently lacking. Sheng-ji Hua-yu (SJHY) ointment is a classical Chinese traditional prescription that can significantly attenuate DU defects, but the specific mechanism remains to be fully elucidated. AIM OF THE STUDY In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs. MATERIALS AND METHODS Modular pharmacology and molecular docking were utilized to predict the therapeutic targets of SJHY ointment against DUs. Male db/db diabetic mice and HaCaT cell models induced by methylglyoxal were used to validate the findings. RESULTS CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm2/day) at the mRNA and protein levels was detected on Day9 after wounding. With CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed. CONCLUSIONS SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1.
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Affiliation(s)
- Dan Yang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
| | - Yi-Mei Tan
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Professional Technical Service Platform for Clinical Evaluation of Skin Health Related Products, Shanghai Science and Technology Commission, Shanghai, 200443, China; NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics, Shanghai, 200443, China; Human Phenome Institute, Fudan University, Shanghai, 200433, China.
| | - Ying Zhang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
| | - Jian-Kun Song
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
| | - Yue Luo
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
| | - Ying Luo
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Xiao-Ya Fei
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
| | - Yi Ru
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
| | - Bin Li
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Jing-Si Jiang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
| | - Le Kuai
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
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Hasan A, Devi Ms S, Sharma G, Narayanan V, Sathiyarajeswaran P, Vinayak S, Sunil S. Vathasura Kudineer, an Andrographis based polyherbal formulation exhibits immunomodulation and inhibits chikungunya virus (CHIKV) under invitro conditions. JOURNAL OF ETHNOPHARMACOLOGY 2023; 302:115762. [PMID: 36181982 DOI: 10.1016/j.jep.2022.115762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/23/2022] [Accepted: 09/24/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chikungunya disease (CHIKD) is caused by the alphavirus, chikungunya virus (CHIKV) and is characterized by acute fever and joint inflammation; the inflammation continues even after clearance of the virus from the system, persisting for several months to years. Currently, there are no modern medicines/vaccines available for its treatment and use of over-the-counter anti-inflammatory generic medicines to relieve symptoms is generally practiced. In India, Indian traditional medicines hold a lot of promise to treat this infection and are routinely used during outbreaks. AIM OF THE STUDY In the present study, we characterized the phytochemical and physicochemical properties of aqueous and ethanol extracts of the Vathasura Kudineer (VSK), a Andrographis based Siddha polyherbal formulation. Additionally, we evaluated its immunomodulatory and antiviral potential using an in vitro system. MATERIALS AND METHODS Aqueous and ethanolic extracts of VSK were prepared and their physico and phytochemical properties were obtained by biochemical and biophysical assays, HPTLC and FTIR. The aqueous extracts of VSK and several of its ingredients were evaluated for their cytotoxicity in Vero cells and using the maximum non-toxic concentration (MNTC), were processed further for evaluating their ability to inhibit CHIKV infection in Vero cells. We performed the co-treatment assay with ethanol extract of VSK and several of its ingredients to assess the antiviral activity against chikungunya virus on Vero cells and through pre-treatment assay (anti-adhesive effect), co-incubation assay (virucidal effect) and post-treatment assay (post-entry effect) were evaluated. Further, we tested the aqueous extract of VSK along with some of its ingredients for their immunomodulatory properties. We performed antioxidant and anti-inflammatory assays using LPS-simulated RAW 264.7 cells. For antioxidant capacity of extracts, we performed extra-cellular ABTS radical scavenging activity and intra-cellular effects on ROS generation and SOD activity. We assessed the effect on most important inflammatory mediators like Nitric oxide (NO) and Prostaglandin E2 (PGE2) and pro-inflammatory cytokines like interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα). RESULTS We provided the fingerprint of the phytochemicals of both ethanol and aqueous extracts of VSK that can be used for identification. We observed that ethanol extract was able to inhibit CHIKV infection at MNTC with 48 h of treatment on Vero cells. Its ingredient VSKI-As (Anethum sowa) found to be most effective to show virucidal effect while VSKI-Cs (Clerodendrum serratum) and VSKI-Pn (Pipper nigrum) found to be effective in post-entry effect. VSK was able to show ABTS radical scavenging activity, reduce ROS generation, inhibit the inflammatory mediators (NO and PGE2) and pro-inflammatory cytokines (IL-1β and TNFα) production in LPS-stimulated RAW 264.7 cells. CONCLUSIONS We provided the evidence that VSK has both immunomodulatory as well as antiviral potential. It shows virucidal as well as post-entry effects on chikungunya virus. VSK can inhibit pro-inflammatory cytokines, IL-1β and TNFα production by suppressing the inflammatory mediators, NO and PGE2.
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Affiliation(s)
- Abdul Hasan
- Vector Borne Disease Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India
| | - Shree Devi Ms
- Siddha Central Research Institute, Chennai, Tamil Nadu, India
| | - Geetika Sharma
- Vector Borne Disease Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India
| | - Vimal Narayanan
- Vector Borne Disease Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India
| | | | - S Vinayak
- Siddha Central Research Institute, Chennai, Tamil Nadu, India
| | - Sujatha Sunil
- Vector Borne Disease Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India.
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Ren MS, Xie HH, Ding Y, Li ZH, Liu B. Er-xian decoction drug-containing serum promotes Mc3t3-e1 cell proliferation and osteogenic differentiation via regulating BK channel. JOURNAL OF ETHNOPHARMACOLOGY 2023; 302:115887. [PMID: 36328203 DOI: 10.1016/j.jep.2022.115887] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 10/13/2022] [Accepted: 10/27/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Er-xian Decoction (EXD) is a well-known prescription widely used to prevent and treat climacteric syndrome and osteoporosis in China. BK channel positively affects osteoblast bone formation in vitro. However, it is still unclear whether the effect of EXD on promoting osteoblasts osteogenic differentiation is related to BK channel. AIM OF THE STUDY The study is aimed at determining whether the EXD-containing serum promotes the proliferation of osteoblasts and their differentiation through BK channel. MATERIALS AND METHODS The chemical compounds of EXD were analyzed by UPLC-Q-TOF/MS. An osteogenic induction medium (OM) was used to induce MC3T3-E1 cells' osteogenic differentiation. The effects of EXD-containing serum and tetraethylammonium (TEA) on the proliferation activity of Mc3t3-e1 cells were detected by CCK-8 assay. ALP activity was determined by an alkaline phosphatase kit. The protein expression (BMP2, OPG, and COL1) was analyzed by Western blot, and the mRNA expression (Runx2, OPG, and BMP2) was assessed by real-time PCR. Alizarin red was used to stain the mineralized region of osteoblasts. In addition, we analyzed the relationship between BK channel and its downstream PTEN/Akt/Foxo1 signaling pathway. RESULTS 72 compounds were identified by UPLC-Q-TOF/MS analysis in EXD. Mangiferin, ferulic acid, berberine, and icariin were main active components of EXD. EXD-containing serum could enhance the cell viability of MC3T3-E1 cells by decreasing the expression of BKα protein. EXD-containing serum increased ALP activity and calcium nodule formation of Mc3t3-e1 cells, promoted the protein expression of BKα, COL1, BMP2, OPG, and the mRNA expression of RUNX2, OPG, and BMP2, however, these effects can be reversed after adding TEA. In addition, EXD-containing serum could upregulate phosphorylation of Akt and Foxo1 in osteogenic-induced Mc3t3-e1 cells, and lower the expression of PTEN. And these effects of EXD-containing serum could be reduced by TEA. CONCLUSIONS The effect of EXD-containing serum on promoting cell proliferation and osteogenic differentiation of Mc3t3-e1 cells might be linked to the regulation of BK channel.
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Affiliation(s)
- Ming-Shi Ren
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China; Key Laboratory of TCM Prevention and Treatment of Senile Disease, Nanchang, 330004, China.
| | - Hui-Hui Xie
- The First Affiliated Hospital of Gannan Medical College, Ganzhou, 341000, China
| | - Yu Ding
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China; Key Laboratory of TCM Prevention and Treatment of Senile Disease, Nanchang, 330004, China
| | - Zi-Han Li
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China; Key Laboratory of TCM Prevention and Treatment of Senile Disease, Nanchang, 330004, China
| | - Bo Liu
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, 330004, China; Key Laboratory of TCM Prevention and Treatment of Senile Disease, Nanchang, 330004, China.
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Hesperidin Induced HePG-2 Cell Apoptosis through ROS-Mediated p53/Bcl-2/Bax and p-mTOR Signaling Pathways. J Food Biochem 2023. [DOI: 10.1155/2023/3788655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Recently, research showed that one of the most common kinds of liver cancer is hepatocellular carcinoma (HCC), which is also the fourth main cause of cancer deaths. In studies regarding chemicals to better treat the disease, hesperidin shows a novel potential in performing anticancer activities, particularly in liver cancer. However, the specific mechanism of hesperidin that causes such activities remains a mystery. Thus, the purpose of this study is to investigate hesperidin’s effect on cell proliferation and activation of ROS-mediated signaling pathways in HePG-2 cells. Hesperidin shows a significant impact on inhibiting HePG-2 cells’ proliferation through induction of cell apoptosis by Bcl-2, Bax, and p53 pathways. Treating cells with hesperidin in a dose-dependent manner shows a significant increase in the apoptotic cell population (sub-G1). Moreover, Hesperidin’s induction of apoptotic activities shows dependence on ROS (reactive oxygen species) overproduction, further affecting the p-mTOR pathways and leading to DNA damage. Hence, the overall data demonstrate that ROS-mediated signaling pathways exhibit mechanisms that may lead to useful information for interpreting hesperidin-induced hepatocarcinoma cell apoptosis.
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Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides. Molecules 2023; 28:molecules28031350. [PMID: 36771015 PMCID: PMC9919897 DOI: 10.3390/molecules28031350] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/14/2023] [Accepted: 01/25/2023] [Indexed: 02/04/2023] Open
Abstract
Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.
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Acute toxic effects of new synthetic cannabinoid on brain: Neurobehavioral and Histological: Preclinical studies. Chem Biol Interact 2023; 370:110306. [PMID: 36528081 DOI: 10.1016/j.cbi.2022.110306] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 11/30/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Abstract
The psychoactive effects of new synthetic cannabinoids (SCs), MDMB-4en-PINACA, are being marketed as a blend of herbs and spices. This study aims to determine the behavioral, neurochemical, histopathological, and immunohistochemical alterations associated with the acute toxicity of MDMB-4en-PINACA compounds. METHODS Adult male albino rats were administered various toxic doses of the drug (1.5, 3, and 6 mg/kg), and behavioral studies were conducted 2 and 24 h later; animals were then sacrificed. Histopathological and neurochemical examinations were performed. Two hours after intraperitoneal. RESULTS Intraperitoneal injection of MDMB-4en-PINACA, horizontal movement, the number of stops, and mobility ratio were significantly impaired, along with coordination and balance. In addition, it led to a decline in spatial learning and memory, and neurotransmitter concentrations decreased significantly in a dose-dependent manner. Further examination of the cerebral cortex and hippocampus histopathology revealed pathological degeneration of small pyramidal cells. CONCLUSION Thus, these findings revealed that MDMB-4en-PINACA interferes with hippocampal function and impairs cognitive performance, highlighting the cognitive risk associated with SC abuse.
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Tang SC, Lu CT, Ko JL, Lin CH, Hsiao YP. Hydroxychloroquine repairs burn damage through the Wnt/β-catenin pathway. Chem Biol Interact 2023; 370:110309. [PMID: 36535310 DOI: 10.1016/j.cbi.2022.110309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/22/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022]
Affiliation(s)
- Sheau-Chung Tang
- Department of Nursing, National Taichung University of Science and Technology, Taichung, 40640, Taiwan
| | - Chun-Te Lu
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jiunn-Liang Ko
- Department of Medical Oncology and Chest Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Cheng-Hui Lin
- Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Yu-Ping Hsiao
- Department of Dermatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
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Qi RB, Wu ZH. Association between COVID-19 and chronic liver disease: Mechanism, diagnosis, damage, and treatment. World J Virol 2023; 12:22-29. [PMID: 36743657 PMCID: PMC9896589 DOI: 10.5501/wjv.v12.i1.22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/03/2022] [Accepted: 11/21/2022] [Indexed: 01/18/2023] Open
Abstract
As the outbreak evolves, our understanding of the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) on the liver has grown. In this review, we discussed the hepatotropic nature of SARS-CoV-2 and described the distribution of receptors for SARS-CoV-2 (e.g., angiotensin-converting enzyme 2) in the vascular endothelium and cholangiocytes of the liver. Also, we proposed mechanisms for possible viral entry that mediate liver injury, such as liver fibrosis. Due to SARS-CoV-2-induced liver damage, many COVID-19 patients develop liver dysfunction, mainly characterized by moderately elevated serum aminotransferase levels. Patients with chronic liver disease (CLD), such as cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, and viral hepatitis, are also sensitive to SARS-CoV-2 infection. We discussed the longer disease duration and higher mortality following SARS-CoV-2 infection in CLD patients. Correspondingly, relevant risk factors and possible mechanisms were proposed, including cirrhosis-related immune dysfunction and liver deco-mpensation. Finally, we discussed the potential hepatotoxicity of COVID-19-related vaccines and drugs, which influence the treatment of CLD patients with SARS-CoV-2 infection. In addition, we suggested that COVID-19 vaccines in terms of immunogenicity, duration of protection, and long-term safety for CLD patients need to be further researched. The diagnosis and treatment for liver injury caused by COVID-19 were also analyzed in this review.
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Affiliation(s)
- Ruo-Bing Qi
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Zheng-Hao Wu
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
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Retzlaff J, Lai X, Berking C, Vera J. Integration of transcriptomics data into agent-based models of solid tumor metastasis. Comput Struct Biotechnol J 2023; 21:1930-1941. [PMID: 36942106 PMCID: PMC10024179 DOI: 10.1016/j.csbj.2023.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 02/06/2023] [Accepted: 02/06/2023] [Indexed: 03/06/2023] Open
Abstract
Recent progress in our understanding of cancer mostly relies on the systematic profiling of patient samples with high-throughput techniques like transcriptomics. With this approach, one can find gene signatures and networks underlying cancer aggressiveness and therapy resistance. However, omics data alone cannot generate insights into the spatiotemporal aspects of tumor progression. Here, multi-level computational modeling is a promising approach that would benefit from protocols to integrate the data generated by the high-throughput profiling of patient samples. We present a computational workflow to integrate transcriptomics data from tumor patients into hybrid, multi-scale cancer models. In the method, we conduct transcriptomics analysis to select key differentially regulated pathways in therapy responders and non-responders and link them to agent-based model parameters. We then determine global and local sensitivity through systematic model simulations that assess the relevance of parameter variations in triggering therapy resistance. We illustrate the methodology with a de novo generated agent-based model accounting for the interplay between tumor and immune cells in a melanoma micrometastasis. The application of the workflow identifies three distinct scenarios of therapy resistance.
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Affiliation(s)
- Jimmy Retzlaff
- Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Xin Lai
- Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Carola Berking
- Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
| | - Julio Vera
- Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
- Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
- Corresponding author at: Laboratory of Systems Tumor Immunology, Department of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
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46
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Sahoo A, Mandal AK, Kumar M, Dwivedi K, Singh D. Prospective Challenges for Patenting and Clinical Trials of Anticancer Compounds from Natural Products: Coherent Review. Recent Pat Anticancer Drug Discov 2023; 18:470-494. [PMID: 36336805 DOI: 10.2174/1574892818666221104113703] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/24/2022] [Accepted: 09/14/2022] [Indexed: 11/09/2022]
Abstract
Cancer is a leading cause of morbidity and mortality worldwide. Each year, millions of people worldwide are diagnosed with cancer, and more than half of them die. Various conventional therapies for cancer, including chemotherapy and radiotherapy, have extreme side effects. Therefore, to minimize the global burden of lethal diseases like cancer, an effective and novel drug must be discovered. Its patent should be acquired to secure the novel medicament. The pharmacological potential of different natural products has made them popular in the healthcare and pharmaceutical industries. Various anticancer compounds are obtained from natural sources such as plants, microbes, and marine and terrestrial animals, including alkaloids, terpenoids, biophenols, enzymes, glycosides, etc. The term "natural products" is defined as the product of secondary or non-essential metabolic processes produced by living organisms (such as plants, invertebrates, and microorganisms). Although more precise definitions of NPs exist, they do not always meet consensus. Others define NPs as small molecules (excluding biomolecules) that emerge from the metabolic reaction. A handful of effective compounds are used currently from natural or analog moieties, and many more are in clinical studies. There is an excellent need for patenting molecules from natural products as the hit lead molecules are derived, isolated, and synthesized from natural products. However, these naturally occurring products may not be patentable under the law because they come from nature. This review highlights why natural products and compounds are hard to patent, under what patent law criteria we can patent these natural products and compounds, patent procedural guideline sources and why researchers prefer publication rather than a patent. Here, various patent scenarios of natural products and compounds for cancer have been given.
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Affiliation(s)
- Ankit Sahoo
- Department of Pharmaceutical Science, Shalom Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture Technology & Sciences, Prayagraj, Uttar Pradesh 211007, India
| | - Ashok Kumar Mandal
- Natural Product Research Laboratory, Thapathali, Kathmandu, Nepal, 44600
| | - Mayank Kumar
- Department of Pharmaceutical Chemistry, Aryakul College of Pharmacy and Research, Natkur, Lucknow, Uttar Pradesh-226002, India
| | - Khusbu Dwivedi
- Department of Pharmaceutics, Shambhunath Institute of Pharmacy Jhalwa, Prayagraj, Uttar Pradesh 211015, India
| | - Deepika Singh
- Department of Pharmaceutical Science, Shalom Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture Technology & Sciences, Prayagraj, Uttar Pradesh 211007, India
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Fan H, Sun Q, Dukenbayev K, Benassi E, Manarbek L, Nurkesh AA, Khamijan M, Mu C, Li G, Razbekova M, Chen Z, Amin A, Xie Y. Carbon nanoparticles induce DNA repair and PARP inhibitor resistance associated with nanozyme activity in cancer cells. Cancer Nanotechnol 2022. [DOI: 10.1186/s12645-022-00144-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Abstract
Background
Quantum nanodots especially carbon nanoparticles (CNPs) have been widely studied in biomedicine in imaging, and drug delivery, but anti-cancer mechanisms remain elusive.
Methods
Here, we investigated a type of cell death induced by food (beet, soybean) derived CNPs in cancer cells and tested whether CNPs induced DNA damage and resistant to anti-cancer agent PARP inhibitor (PARPi) could be overcome by quantum calculations, TEM, AFM, FT-IR, soft agar assay, and cytotoxicity assay.
Results
At high doses, CNPs derived from beet lead to a pop-like apoptosis (Carbopoptosis) in cancer cells. Quantum mechanical calculations confirmed CNPs binding with phosphate groups as well as DNA bases. At low doses, CNPs develop PARPi drug resistance through interactions between CNPs and PARPi. A synergistic drug effect was achieved with the combination of phosphatase inhibitor (PPi), PARPi, and CNPs. This is corroborated by the fact that sulfur modulated CNPs which exhibit super high phosphatase nanozyme activity abrogated the CNPs induced colony formation in anchorage-independent cancer cell growth.
Conclusion
Thus, our data suggest the CNPs intrinsic nanozyme activity of phosphatase may crosstalk with drug resistance, which can be reversed upon modulations.
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Ma Q, Zhang AN, Zhang CX. Exploration of the Pharmacological Mechanism of Bufei Nashen Pill in Treating Chronic Obstructive Pulmonary Disease Using Network Pharmacology Integrated Molecular Docking. Nat Prod Commun 2022. [DOI: 10.1177/1934578x221134883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Objective: Based on network pharmacological analysis and molecular docking verification, the therapeutic mechanism of Bufei Nashen Pill (BFNSP) in treating chronic obstructive pulmonary disease (COPD) is discussed. Methods: First, the active ingredients and therapeutic targets of BFNSP were determined based on literature and the Chinese medicine system pharmacology database. Relevant targets of COPD were determined using GeneCard, Therapeutic Target Database and Online Mendelian Inheritance in Man (OMIM). The con-targets of BFNSP and COPD were then obtained through the Veen platform, which were implemented in Cytoscape to build “Drug-Ingredients-Potential Target network.” Target gene function enrichment analysis and signal pathway analysis were performed based on STRING database, Database for Annotation, Visualization, and Integrated Discovery, and Kyoto Encyclopedia of Genes and Genomes Pathway database. Finally, SYBYL 2.2.1 software was used to finish docking. Results: In the Drug-Ingredients-Potential Targets network, 172 active ingredients and 183 potential targets were found. Enrichment analysis showed that potential targets mainly involve biological functions such as inflammation, reactive oxygen, and immunity. Molecular docking showed that the active ingredients of BFNSP had preferential interaction with interleukin 6, mitogen-activated protein kinase 1, SRC, epidermal growth factor receptor, and matrix metalloproteinase-9. Conclusion: BFNSP can be used to treat COPD by the regulation of inflammation, immunity, and hypoxia tolerance.
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Affiliation(s)
- Qin Ma
- Ningxia Medical University, Yinchuan, China
- Ningxia Chinese Medicine Research Center, Yinchuan, China
| | - An-ni Zhang
- School of Medicine, Jinan University, Guangzhou, China
| | - Chang-xi Zhang
- Ningxia Chinese Medicine Research Center, Yinchuan, China
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Singla RK, Sharma P, Kumar D, Gautam RK, Goyal R, Tsagkaris C, Dubey AK, Bansal H, Sharma R, Shen B. The role of nanomaterials in enhancing natural product translational potential and modulating endoplasmic reticulum stress in the treatment of ovarian cancer. Front Pharmacol 2022; 13:987088. [PMID: 36386196 PMCID: PMC9643842 DOI: 10.3389/fphar.2022.987088] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/03/2022] [Indexed: 10/21/2023] Open
Abstract
Ovarian cancer, and particularly its most frequent type, epithelial ovarian carcinoma, constitutes one of the most dangerous malignant tumors among females. Substantial evidence has described the potential of phytochemicals against ovarian cancer. The effect of natural compounds on endoplasmic reticulum (ER) stress is of great relevance in this regard. In ovarian cancer, the accumulation of misfolded proteins in the ER lumen results in decompensated ER stress. This leads to deregulation in the physiological processes for the posttranslational modification of proteins, jeopardizes cellular homeostasis, and increases apoptotic signaling. Several metabolites and metabolite extracts of phytochemical origin have been studied in the context of ER stress in ovarian cancer. Resveratrol, quercetin, curcumin, fucosterol, cleistopholine, fucoidan, and epicatechin gallate, among others, have shown inhibitory potential against ER stress. The chemical structure of each compound plays an important role concerning its pharmacodynamics, pharmacokinetics, and overall effectiveness. Studying and cross-comparing the chemical features that render different phytochemicals effective in eliciting particular anti-ER stress actions can help improve drug design or develop multipotent combination regimens. Many studies have also investigated the properties of formulations such as nanoparticles, niosomes, liposomes, and intravenous hydrogel based on curcumin and quercetin along with some other phytomolecules in ovarian cancer. Overall, the potential of phytochemicals in targeting genetic mechanisms of ovarian cancer warrants further translational and clinical investigation.
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Affiliation(s)
- Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
| | - Pooja Sharma
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India
- Khalsa College of Pharmacy, Amritsar, India
| | - Dinesh Kumar
- Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh, India
| | - Rupesh K. Gautam
- Department of Pharmacology, Indore Institute of Pharmacy, IIST Campus, Opposite IIM Indore, Indore, India
| | - Rajat Goyal
- MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, India
| | | | | | - Himangini Bansal
- Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, BHU, Varanasi, India
| | - Bairong Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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Bian Z, Li C, Peng D, Wang X, Zhu G. Use of Steaming Process to Improve Biochemical Activity of Polygonatum sibiricum Polysaccharides against D-Galactose-Induced Memory Impairment in Mice. Int J Mol Sci 2022; 23:ijms231911220. [PMID: 36232521 PMCID: PMC9570032 DOI: 10.3390/ijms231911220] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/16/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Polysaccharide from Polygonatum sibiricum (PSP) possesses antioxidant, antiaging, and neuroprotective activities. However, whether and how the steaming process influences the biological activities of PSP, especially against aging-related memory impairment, is not yet known. In this study, Polygonatum sibiricum rhizome was subjected to a “nine steaming and nine drying” process, then PSPs with different steaming times were abstracted. Thereafter, the physicochemical properties were qualified; the antioxidant activities of PSPs were evaluated in a D-gal-induced HT-22 cell model, and the effects of PSPs (PSP0, PSP5 and PSP9) on memory was evaluated using D-gal-injured mice. Our results showed that while the steamed PSPs had a low pH value and a large negative charge, they shared similar main chains and substituents. Cellular experiments showed that the antioxidant activity of steamed PSPs increased. PSP0, PSP5, and PSP9 could significantly ameliorate the memory impairment of D-gal-injured mice, with PSP5 showing the optimal effect. Meanwhile, PSP5 demonstrated the best effect in terms of preventing cell death and synaptic injury in D-gal-injured mice. Additionally, the steamed PSPs increased anti-oxidative stress-related protein expression and decreased inflammation-related protein expression in D-gal-injured mice. Collectively, the steaming process improves the effects of PSPs against D-gal-induced memory impairment in mice, likely by increasing the antioxidant activity of PSPs.
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Affiliation(s)
| | | | | | - Xuncui Wang
- Correspondence: (X.W.); (G.Z.); Tel.: +86-551-68129051 (X.W.); +86-551-68129028 (G.Z.)
| | - Guoqi Zhu
- Correspondence: (X.W.); (G.Z.); Tel.: +86-551-68129051 (X.W.); +86-551-68129028 (G.Z.)
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