|
1
|
Aliyari M, Ghoflchi S, Hashemy SI, Hashemi SF, Reihani A, Hosseini H. The PI3K/Akt pathway: a target for curcumin's therapeutic effects. J Diabetes Metab Disord 2025; 24:52. [PMID: 39845908 PMCID: PMC11748622 DOI: 10.1007/s40200-025-01563-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/05/2025] [Indexed: 01/24/2025]
Abstract
Purpose The purpose of this review study is to investigate the effect of curcumin on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in various diseases. Curcumin, the main compound found in turmeric, has attracted a lot of attention for its diverse pharmacological properties. These properties have increased the therapeutic potential of curcumin in chronic diseases such as cardiovascular disease, Type 2 diabetes, obesity, non-alcoholic fatty liver disease, kidney disease, and neurodegenerative diseases. One of the main mechanisms of the effect of curcumin on health is its ability to modulate the PI3K/Akt signaling pathway. This pathway plays an important role in regulating vital cellular processes such as growth, cell survival, metabolism, and apoptosis. Disruption of the PI3K/Akt signaling pathway is associated with the incidence of several diseases. Methods Electronic databases including PubMed, Google Scholar, and Scopus were searched with the keywords "phosphoinositide 3-kinase" AND "protein kinase B "AND "curcumin" in the title/abstract. Also, following keywords "non-alcoholic fatty liver disease" AND "diabetes" AND "obesity" AND "kidney disease" and "neurodegenerative diseases" was searched in the whole text. Results Research indicates that curcumin offers potential benefits for several health conditions. Studies have shown it can help regulate blood sugar, reduce inflammation, and protect the heart, kidneys, and brain. Conclusion This protective effect is partially achieved by regulating the PI3K-Akt survival pathway, which helps improve metabolic disorders and oxidative stress. By examining how curcumin affects this vital cell pathway, researchers can discover new treatment strategies for a range of diseases.
Collapse
Affiliation(s)
- Mahdieh Aliyari
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Ghoflchi
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedeh Fatemeh Hashemi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirali Reihani
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseini
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
2
|
Kim MJ, Yang YJ, Heo JW, Son JD, You YZ, Yang JH, Park KI. Potential Chondroprotective Effect of Artemisia annua L. Water Extract on SW1353 Cell. Int J Mol Sci 2025; 26:1901. [PMID: 40076528 PMCID: PMC11899987 DOI: 10.3390/ijms26051901] [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: 02/04/2025] [Revised: 02/21/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Inflammation plays a critical role in the pathogenesis of osteoarthritis (OA). The objective of this study was to investigate the anti-inflammatory and chondroprotective properties of Artemisia annua L. water extract (AWE) following the induction of inflammation in cartilage cells (SW1353 cell) through the administration of interleukin-1 beta (IL-1β). We demonstrated significant antioxidant activity, as evidenced by elevated total phenolic and flavonoid content, in addition to robust free radical scavenging capacity, as assessed through DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. Its cytotoxic effects were assessed at a concentration of 200 μg/mL, where no cytotoxic signs were observed in SW1353 cells treated with IL-1β; the levels of reactive oxygen species (ROS) were notably reduced in a dose-dependent manner. The principal inflammatory markers, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), were significantly diminished by AWE treatment. AWE administration led to a dose-dependent reduction in the expression of key proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathways, ultimately resulting in a decrease in the release of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-13, which are known to contribute to cartilage degradation. Additionally, the levels of degraded collagen type II in the cartilage cells were restored. These findings suggest that reducing oxidative stress and inflammation, along with inhibiting activated MAPK and NF-κB signaling pathways, may ameliorate the progression of IL-1β-induced OA. Furthermore, a molecular docking analysis revealed a strong binding affinity of MMP-13, a critical mediator in the pathogenesis of OA. Six compounds were identified in AWE, corroborating its potential antioxidant and anti-inflammatory effects. Therefore, AWE may serve as a potentially useful therapeutic agent against OA by modulating inflammation-related mechanisms.
Collapse
Affiliation(s)
- Min Jung Kim
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| | - Ye Jin Yang
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| | - Ji Woong Heo
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| | - Jae-dong Son
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| | - Young Zoo You
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| | - Ju-Hye Yang
- Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, 70 Cheomdan-ro, Dong-gu, Daegu 41062, Republic of Korea;
| | - Kwang Il Park
- Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Gazwa, Jinju 52828, Republic of Korea; (M.J.K.); (Y.J.Y.); (J.W.H.); (J.-d.S.); (Y.Z.Y.)
| |
Collapse
|
|
3
|
Wu M, Li K, Wu J, Ding X, Ma X, Wang W, Xiao W. Ginsenoside Rg1: A bioactive therapeutic agent for diverse liver diseases. Pharmacol Res 2025; 212:107571. [PMID: 39756553 DOI: 10.1016/j.phrs.2024.107571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/10/2024] [Accepted: 12/29/2024] [Indexed: 01/07/2025]
Abstract
Diverse liver diseases are characterised by late diagnosis and rapid progression and have become one of the major threats to human health. To delay the transition from benign tissue lesions to a substantial organ injury, scientists have gradually applied natural compounds derived from plants as a complementary therapy in the field of hepatology. Ginseng (Panax ginseng C. A. Meyer) is a tonic traditional Chinese herbal medicine, and natural products, including ginsenoside Rg1 (G-Rg1), which is a kind of 20(S)-protopanaxatriol saponin with a relatively high biological activity, can be isolated from the roots or stems of ginseng. Given these information, this review aimed to summarise and discuss the metabolic mechanisms of G-Rg1 in the regulation of diverse liver diseases and the measures to improve its bioavailability. As a kind of monomer in Chinese medicine with multitarget pharmacological effects, G-Rg1 can provide significant therapeutic benefits in the alleviation of alcoholic liver disease, nonalcoholic fatty liver disease, liver fibrosis, viral hepatitis, etc., which mainly rely on the inhibition of apoptosis, strengthening endogenous anti-inflammatory and antioxidant mechanisms, activation of immune responses and regulation of efflux transport signals, to improve pathological changes in the liver caused by lipid deposition, inflammation, oxidative stress, accumulation of hepatotoxic product, etc. However, the poor bioavailability of G-Rg1 must be overcome to improve its clinical application value. In summary, focusing on the hepatoprotective benefits of G-Rg1 will provide new insights into the development of natural Chinese medicine resources and their pharmaceutical products to target the treatment of liver diseases.
Collapse
Affiliation(s)
- Mingyu Wu
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Ke Li
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Jiabin Wu
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Xianyi Ding
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Xiaotong Ma
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Wenhong Wang
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| | - Weihua Xiao
- Shanghai Key Lab of Human Performance (Shanghai University of sport), Shanghai University of Sport, Shanghai 200438, China; The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.
| |
Collapse
|
|
4
|
Munakarmi S, Gurau Y, Shrestha J, Chand L, Park HS, Lee GH, Jeong YJ. trans-chalcone ameliorates CCl4-induced acute liver injury by suppressing endoplasmic reticulum stress, oxidative stress and inflammation. Pathol Res Pract 2024; 263:155663. [PMID: 39437640 DOI: 10.1016/j.prp.2024.155663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 10/13/2024] [Accepted: 10/16/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Acute liver injury serves as a crucial marker for detecting liver damage due to toxic, viral, metabolic, and autoimmune exposures. Due to the response to adverse external stimuli and various cellular homeostasis, Endoplasmic reticulum stress (ERS), Oxidative stress, and Inflammation have great potential for treating liver injury. Trans-chalcones (TC) is a polyphenolic compound derived from a natural plant with anti-oxidative and anti-inflammatory abilities. Here, TC was aimed to attenuate liver injury by triggering ER stress, oxidative stress, inflammation, and apoptosis. A single dose of carbon tetrachloride (CCl4) 1 mL/kg was administered intraperitoneally into C57BL6 mice to construct an in vivo NAFLD model, whereas AML12 cells were treated with lipopolysaccharides (LPS) to construct an in vitro NAFLD model. The mice used in the experiment were randomly assigned to two groups: a 12-hour set and a 24-hour set. Forty-nine mice were randomly divided into seven groups, the control group (Group I), TC group (Group II) 10 mg/kg TC, negative control group (Group III) CCl4, TC + CCl4 groups (Groups IV-VI), mice were subcutaneously treated with (5, 10, and 20) mg/kg of TC for three consecutive days before the CCl4 injection and the positive control group (Group VII) received 10 mg/kg Silymarin. After the experiment, serum transaminase, liver histological pathology, hepatic expression levels ERS, oxidative stress, and inflammation-related markers were assessed. TC pre-treatment significantly alleviates the expression of ER stress, oxidative stress, inflammatory cytokines, and apoptosis in both in vivo and in vitro models of liver injury. TC treatment significantly reduced serum transaminase levels (ALT and AST), and improved liver histopathological scores. TC administration also led to a reduction in MDA levels and the suppression of ROS generated by CCl4 in hepatic tissue, which contributed to an increase in GSH levels. The protective effect of TC on the liver injury mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, TC pre-treatment dramatically decreased the protein levels of ER stress indicators such as CHOP, Bip, Ero-Lα, IRE1α, PERK, Calnexin, and PDI when compared to the CCl4-only treated group. TC exerts hepatoprotective effects against CCl4-induced acute liver injuries in mice by modulating ERS, oxidative stress, and inflammation. These results suggest that TC pre-treatment at a dose of (20 mg/kg BW) was as effective as silymarin (10 mg/kg) in preventing CCl4-induced acute liver injury. Further investigations are necessary to elucidate the precise molecular mechanisms underlying the hepatoprotective effects of TC and to explore its therapeutic potential in clinical trials.
Collapse
Affiliation(s)
- Suvesh Munakarmi
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea.
| | - Yamuna Gurau
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea.
| | - Juna Shrestha
- Alka Hospital Private Limited, Jwalakhel, Kathmandu 446010, Nepal.
| | - Lokendra Chand
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea; Department of Chemistry, Korea University, Seoul 02841, Korea
| | - Ho Sung Park
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea; Department of Pathology, Jeonbuk National University Medical School, Jeonju 54907, Korea
| | - Geum-Hwa Lee
- Department of Pharmacology and New Drug Development Research Institute, Jeonbuk National Hospital, Jeonju 54907, Korea.
| | - Yeon Jun Jeong
- Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea; Division of Pediatric Surgery, Department of Surgery, Jeonbuk National University Medical School, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea.
| |
Collapse
|
|
5
|
Aliyari M, Hashemy SI, Hashemi SF, Reihani A, Kesharwani P, Hosseini H, Sahebkar A. Targeting the Akt signaling pathway: Exploiting curcumin's anticancer potential. Pathol Res Pract 2024; 261:155479. [PMID: 39068859 DOI: 10.1016/j.prp.2024.155479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/13/2024] [Accepted: 07/19/2024] [Indexed: 07/30/2024]
Abstract
Cancer is recognized as one of the leading causes of death worldwide. In recent years, advancements in early detection and expanding treatment options have contributed to a decrease in mortality rates. However, the emergence of drug-resistant cancers necessitates the exploration of innovative and more effective drugs. The Akt kinases play a central role in various signaling pathways that regulate crucial cellular processes, including cell growth, proliferation, survival, angiogenesis, and glucose metabolism. Due to frequent disruptions of the Akt signaling pathway in numerous human cancers and its broad biological implications, targeting this pathway has become a key focus in combating tumor aggressiveness and a promising avenue for therapeutic intervention. Curcumin, a compound found in turmeric, has been extensively studied for its potential as an anti-cancer agent. It demonstrates inhibitory effects on cancer initiation, progression, and metastasis by influencing various processes involved in tumor growth and development. These effects are achieved through negative regulation of transcription factors, growth factors, cytokines, protein kinases, and other oncogenic molecules. This review aims to explore curcumin's anticancer activity against different types of cancer mediated via the PI3K/Akt signaling pathway, as well as its practical applications in treatment.
Collapse
Affiliation(s)
- Mahdieh Aliyari
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyedeh Fatemeh Hashemi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirali Reihani
- Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India
| | - Hossein Hosseini
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
6
|
Hwang S, Eom YW, Kang SH, Baik SK, Kim MY. IFN-β Overexpressing Adipose-Derived Mesenchymal Stem Cells Mitigate Alcohol-Induced Liver Damage and Gut Permeability. Int J Mol Sci 2024; 25:8509. [PMID: 39126076 PMCID: PMC11313321 DOI: 10.3390/ijms25158509] [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: 06/17/2024] [Revised: 08/01/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024] Open
Abstract
Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-β) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-β gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-β, C57BL/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-β. Mice treated with binge alcohol and administered ASC-IFN-β showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-β also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-β or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-β overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF.
Collapse
Affiliation(s)
- Soonjae Hwang
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, Republic of Korea;
- Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea; (Y.W.E.); (S.K.B.)
- Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea
| | - Young Woo Eom
- Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea; (Y.W.E.); (S.K.B.)
- Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea
| | - Seong Hee Kang
- Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Republic of Korea;
| | - Soon Koo Baik
- Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea; (Y.W.E.); (S.K.B.)
- Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea
| | - Moon Young Kim
- Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea; (Y.W.E.); (S.K.B.)
- Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea
| |
Collapse
|
|
7
|
Ning S, Chen Y, Shao J, Zhu H, Zhang Z, Miao J. The effects of acteoside on locomotor recovery after spinal cord injury - The role of autophagy and apoptosis signaling pathway. Biomed Pharmacother 2024; 175:116607. [PMID: 38692056 DOI: 10.1016/j.biopha.2024.116607] [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: 01/24/2024] [Revised: 04/09/2024] [Accepted: 04/17/2024] [Indexed: 05/03/2024] Open
Abstract
In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1β and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3 kcal/mol, -8.3 kcal/mol, and -8.5 kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.
Collapse
Affiliation(s)
- Shanglong Ning
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Yang Chen
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Jia Shao
- Department of Spine Surgery, Henan Provincial People's Hospital, Zhengzhou 450003, China
| | - Hui Zhu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300000, China
| | - Zepei Zhang
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Jun Miao
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China.
| |
Collapse
|
|
8
|
Tang X, Zhou Y, Liu F, Wang B, Mao B, Zhang Q, Zhao J, Chen W, Cui S. A Pueraria lobata root extract alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating the gut microbiota and associated metabolites. FOOD BIOSCI 2024; 59:103746. [DOI: 10.1016/j.fbio.2024.103746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
9
|
Islam Shawon S, Nargis Reyda R, Qais N. Medicinal herbs and their metabolites with biological potential to protect and combat liver toxicity and its disorders: A review. Heliyon 2024; 10:e25340. [PMID: 38356556 PMCID: PMC10864916 DOI: 10.1016/j.heliyon.2024.e25340] [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: 09/08/2023] [Revised: 01/22/2024] [Accepted: 01/24/2024] [Indexed: 02/16/2024] Open
Abstract
The liver is an essential organ that helps the body with immunity, metabolism, and detoxification, among other functions. Worldwide, liver illnesses are a leading cause of mortality and disability. There are few effective treatment choices, but they frequently have unfavorable side effects. Investigating the potential of medicinal plants and their bioactive phytoconstituents in the prevention and treatment of liver disorders has gained more attention in recent years. An assessment of the hepatoprotective potential of medicinal plants and their bioactive secondary metabolites is the goal of this thorough review paper. To determine their hepatoprotective activity, these plants were tested against liver toxicity artificially induced in rats, mice and rabbits by chemical agents such as carbon tetrachloride (CCl4), paracetamol (PCM), thioacetamide (TAA), N-nitrosodiethylamine, d-galactosamine/lipopolysaccharide, antitubercular medicines (rifampin, isoniazid) and alcohol. To find pertinent research publications published between 1989 and 2022, a comprehensive search of electronic bibliographic databases (including Web of Science, SpringerLink, ScienceDirect, Google Scholar, PubMed, Scopus, and others) was carried out. The investigation comprised 203 plant species from 81 families in total. A thorough discussion was mentioned regarding the hepatoprotective qualities of plants belonging to several families, such as Fabaceae, Asteraceae, Lamiaceae, and Euphorbiaceae. The plant groups Asteraceae and Fabaceae were the most frequently shown to have hepatoprotective properties. The phytochemical constituents namely flavonoids, phenolic compounds, and alkaloids exhibited the highest frequency of hepatoprotective action. Also, some possible mechanism of action of some active constituents from medicinal plants was discussed in brief which were found in some studies. In summary, the information on medicinal plants and their potentially hepatoprotective bioactive phytoconstituents has been consolidated in this review which emphasizes the importance of further research to explore the efficacy and safety of these natural remedies for various liver ailments.
Collapse
Affiliation(s)
- Shahparan Islam Shawon
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Rashmia Nargis Reyda
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| | - Nazmul Qais
- Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
| |
Collapse
|
|
10
|
Zhang X, Zhang Q, Yu M, Zhang Y, He T, Qiu Z, Qiu Y, Wang W. Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117349. [PMID: 38380572 DOI: 10.1016/j.jep.2023.117349] [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: 07/18/2023] [Revised: 10/20/2023] [Accepted: 10/22/2023] [Indexed: 02/22/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. AIM OF THE STUDY This paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. MATERIALS AND METHODS Firstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. RESULTS The results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1β), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. CONCLUSIONS In conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.
Collapse
Affiliation(s)
- Xiaoxu Zhang
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Qi Zhang
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Menghan Yu
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Yanfei Zhang
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China; School of Pharmacy, Jilin Medical University, Jilin, 132013, China.
| | - Tianzhu He
- School of Basic Medical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Zhidong Qiu
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Ye Qiu
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| | - Weinan Wang
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, China.
| |
Collapse
|
|
11
|
Li JZ, Chen N, Ma N, Li MR. Mechanism and Progress of Natural Products in the Treatment of NAFLD-Related Fibrosis. Molecules 2023; 28:7936. [PMID: 38067665 PMCID: PMC10707854 DOI: 10.3390/molecules28237936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/22/2023] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disorder worldwide, with liver fibrosis (LF) serving as a pivotal juncture in NAFLD progression. Natural products have demonstrated substantial antifibrotic properties, ushering in novel avenues for NAFLD treatment. This study provides a comprehensive review of the potential of natural products as antifibrotic agents, including flavonoids, polyphenol compounds, and terpenoids, with specific emphasis on the role of Baicalin in NAFLD-associated fibrosis. Mechanistically, these natural products have exhibited the capacity to target a multitude of signaling pathways, including Hedgehog, Wnt/β-catenin, TGF-β1, and NF-κB. Moreover, they can augment the activities of antioxidant enzymes, inhibit pro-fibrotic factors, and diminish fibrosis markers. In conclusion, this review underscores the considerable potential of natural products in addressing NAFLD-related liver fibrosis through multifaceted mechanisms. Nonetheless, it underscores the imperative need for further clinical investigation to authenticate their effectiveness, offering invaluable insights for future therapeutic advancements in this domain.
Collapse
Affiliation(s)
- Jin-Zhong Li
- Division of Infectious Disease, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Ning Chen
- General Medicine, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Nan Ma
- Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Min-Ran Li
- Division of Infectious Disease, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| |
Collapse
|
|
12
|
Dubey A, Dasgupta T, Devaraji V, Ramasamy T, Sivaraman J. Investigating anti-inflammatory and apoptotic actions of fucoidan concentrating on computational and therapeutic applications. 3 Biotech 2023; 13:355. [PMID: 37810192 PMCID: PMC10558419 DOI: 10.1007/s13205-023-03771-0] [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: 04/04/2023] [Accepted: 09/08/2023] [Indexed: 10/10/2023] Open
Abstract
Fucoidan is linked to a variety of biological processes. Differences in algae species, extraction, seasons, and locations generate structural variability in fucoidan, affecting its bioactivities. Nothing is known about fucoidan from the brown alga Dictyota bartayresiana, its anti-inflammatory properties, or its inherent mechanism. This study aimed to investigate the anti-inflammatory properties of fucoidan isolated from D. bartayresiana against LPS-induced RAW 264.7 macrophages and to explore potential molecular pathways associated with this anti-inflammatory effects. Fucoidan was first isolated and purified from D. bartayresiana, and then, MTT assay was used to determine the effect of fucoidan on cell viability. Its effects on reactive oxygen species (ROS) formation and apoptosis were also studied using the ROS assay and acridine orange/ethidium bromide fluorescence labelling, respectively. Molecular docking and molecular dynamics simulation studies were performed on target proteins NF-κB and TNF-α to identify the route implicated in these inflammatory events. It was observed that fucoidan reduced LPS-induced inflammation in RAW 264.7 cells. Fucoidan also decreased the LPS-stimulated ROS surge and was found to induce apoptosis in the cells. Molecular docking and molecular dynamics simulation studies revealed that fucoidan's potent anti-inflammatory action was achieved by obstructing the NF-κB signalling pathway. These findings were particularly noteworthy and novel because fucoidan isolated from D. bartayresiana had not previously been shown to have anti-inflammatory properties in RAW 264.7 cells or to exert its activity by obstructing the NF-κB signalling pathway. Conclusively, these findings proposed fucoidan as a potential pharmaceutical drug for inflammation-related diseases.
Collapse
Affiliation(s)
- Akanksha Dubey
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632 014 India
| | - Tiasha Dasgupta
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632 014 India
| | - Vinod Devaraji
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632 014 India
| | - Tamizhselvi Ramasamy
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632 014 India
| | - Jayanthi Sivaraman
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632 014 India
| |
Collapse
|
|
13
|
Mao J, Tan L, Tian C, Wang W, Zhang H, Zhu Z, Li Y. Hepatoprotective effect of syringin combined with costunolide against LPS-induced acute liver injury in L-02 cells via Rac1/AKT/NF-κB signaling pathway. Aging (Albany NY) 2023; 15:11994-12020. [PMID: 37916984 PMCID: PMC10683587 DOI: 10.18632/aging.205161] [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: 08/10/2023] [Accepted: 10/02/2023] [Indexed: 11/03/2023]
Abstract
Acute liver injury (ALI) leads to abnormal liver function and damage to liver cells. Syringin (syr) and costunolide (cos) are the major extracts from Dolomiaea souliei (Franch.) C.Shih (D. souliei), showing diverse biological functions in various biological processes. We explored the underlying hepatoprotective effects of syr+cos against LPS-induced ALI. Cell viability and proliferation were assessed using an MTT assay and immunofluorescence staining. Flow cytometry analysis was used to detect cell cycle distribution and apoptosis. ELISA was utilized to measure liver function and antioxidant stress indexes. qRT-PCR and western blotting was performed to determine mRNA and protein levels respectively. Using shRNA approach to Rac1 analyzed transcriptional targets. The results showed that syr+cos promoted L-02 cell proliferation, inhibiting the cell apoptosis and blocking cell cycle in G1 and G2/M phase. Syr+cos decreased the production of ALT, AST, LDH, MDA and ROS while increased SOD and CAT activities. Pretreated with syr+cos may decrease expressions of caspase-3,7,9, NF-κB, TNF-α proteins, Cyclin B, CDK1 and p-IκB proteins while p-IκB increased. Silencing of Rac-1 may protect the liver by increasing AKT, S473, T308 and reducing p-AKT proteins. Syr+cos exhibits anti-ALI activity via Rac1/AKT/NF-κB signaling pathway which might act as an effective candidate drug for the treatment of ALI.
Collapse
Affiliation(s)
- Jingxin Mao
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Lihong Tan
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Cheng Tian
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Wenxiang Wang
- Chongqing Three Gorges Medical College, Chongqing 404120, China
| | - Hao Zhang
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Zhaojing Zhu
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| | - Yan Li
- Chongqing Medical and Pharmaceutical College, Chongqing 400030, China
- Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing 400030, China
| |
Collapse
|
|
14
|
Wang L, Yan F, Zhang J, Xiao Y, Wang C, Zhu Y, Li C, Liu Z, Li W, Wang C, Liu J, Zhang H, Xiong H, Shi D. Cornuside improves murine autoimmune hepatitis through inhibition of inflammatory responses. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 120:155077. [PMID: 37716032 DOI: 10.1016/j.phymed.2023.155077] [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: 04/11/2023] [Revised: 08/08/2023] [Accepted: 09/09/2023] [Indexed: 09/18/2023]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) poses an important public health concern worldwide, with few therapeutic options available. Cornuside, a primary cornel iridoid glycoside present in Cornus officinalis Sieb. et Zucc., is a well-known traditional Chinese medicine that possesses anti-inflammatory, antioxidant and anti-apoptotic properties. However, the effects of cornuside on autoimmune diseases including AIH is still not defined, neither is clear on the mechanisms of cornuside in the suppression of inflammatory responses. PURPOSE The study was aimed to investigate the therapeutic effects of cornuside on AIH using murine models. STUDY DESIGN A murine model of AIH induced by concanavalin A (Con A) was used to examine the pharmacological activity of cornuside in suppressing the inflammatory responses in vivo. METHODS C57BL/6J mice were intravenously with different doses of cornuside and challenged with 18 mg/kg Con A 3 h later. Network pharmacological analysis was performed to identify the potential target genes and signaling pathways by cornuside in AIH. Next serum and liver tissues were collected 12 h after Con A injection to analyze the levels of markers for hepatic injury, apoptosis, oxidative stress, immune responses, and inflammation. RESULTS Network pharmacological analysis revealed that cornuside may modulate oxidative stress and apoptosis in AIH. Compared with the Con A group, cornuside pretreatment significantly reduced the serum levels of alanine aminotransferase and aspartate aminotransferase, improving histopathological damage and apoptosis in the livers. In addition, cornuside decreased the levels of malondialdehyde, myeloperoxidase, but increased superoxide dismutase levels, suggesting the relieving of oxidative stress. Furthermore, cornuside suppressed the activation of T and natural killer T cells, whereas the proportion of myeloid-derived suppressor cells was significantly increased. The production of proinflammatory cytokines, including interleukin (IL)-6, IL-12, IL-1β, and tumor necrosis factor-alpha (TNF-α), was also clearly decreased. Finally, western blot analysis displayed that cornuside inhibited the phosphorylation of extracellular receptor kinase (ERK) and c-Jun N-terminal kinase (JNK). CONCLUSIONS We demonstrated that cornuside has protective effects for Con A-induced immune-mediated hepatitis by suppressing the oxidative stress, apoptosis, and the inflammatory responses through the ERK and JNK signaling pathways, as well as by modulating the activation and recruitment of immune cells.
Collapse
Affiliation(s)
- Lin Wang
- Cheeloo College of Medicine, Shandong University, Jinan, China; Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
| | - Fenglian Yan
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Junfeng Zhang
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Yucai Xiao
- Cheeloo College of Medicine, Shandong University, Jinan, China; Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
| | - Changying Wang
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Yuanbo Zhu
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Chunxia Li
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Zhihong Liu
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China
| | - Wenbo Li
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
| | - Chengduo Wang
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
| | - Jie Liu
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
| | - Hui Zhang
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China.
| | - Huabao Xiong
- Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China; Jining Key Laboratory of Immunology, Jining Medical University, Jining, China.
| | - Dongmei Shi
- Cheeloo College of Medicine, Shandong University, Jinan, China; Laboratory of Medical Mycology, Department of Dermatology, Jining No.1 People's Hospital, Jining, China.
| |
Collapse
|
|
15
|
Bogahawaththa S, Kawamura T, Bandaranayake U, Hirakawa T, Yamada G, Ishino H, Hirohashi T, Kawaguchi SI, Wijesundera KK, Wijayagunawardane MPB, Ishimaru K, Kodithuwakku SP, Tsujita T. Identification and mechanistic investigation of ellagitannins from Osbeckia octandra that attenuate liver fibrosis via the TGF-β/SMAD signaling pathway. Biosci Biotechnol Biochem 2023; 87:1295-1309. [PMID: 37580142 DOI: 10.1093/bbb/zbad114] [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: 06/20/2023] [Accepted: 08/04/2023] [Indexed: 08/16/2023]
Abstract
Fibrosis is a major problem in chronic liver disease with limited treatment options due to its complex nature. Herbal medicines are often used as an alternative. The aim of this study was to investigate the therapeutic potential of Osbeckia octandra and to identify its active compounds and regulatory pathways. The effects of crude leaf suspension and boiled leaf extract were investigated in an animal model, and the extract was found to be the more effective treatment. Three major bioactive compounds, pedunculagin, casuarinin, and gallic acid, were isolated from the extract using the hepatic stellate cell line, LX-2-based antifibrotic effect evaluation system. The results showed that all these compounds ameliorated LX-2 in fibrotic state. This inhibitory mechanism was confirmed through the TGF-β/SMAD signaling pathway. Collectively, the presence of these compounds in O. octandra suggests its potential as a treatment for liver fibrosis.
Collapse
Affiliation(s)
- Sudarma Bogahawaththa
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0065, Japan
- Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan
- Department of Animal Science, Faculty of Agriculture, University of Peradeniya, Peradeniya, 20400, Sri Lanka
| | - Tomoaki Kawamura
- Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan
| | - Udari Bandaranayake
- Department of Animal Science, Faculty of Agriculture, University of Peradeniya, Peradeniya, 20400, Sri Lanka
- Department of Functional Material Science, Graduate School of Science and Engineering, Saitama University, Shimo-Okubo 225, Sakura-ku, Saitama, 338-8570, Japan
| | - Tomoaki Hirakawa
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0065, Japan
- Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan
| | - Goki Yamada
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0065, Japan
- Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan
| | - Hana Ishino
- Department of Biological Resource Sciences, Faculty of Agriculture, Saga University, 1 Honjo, Saga, 840-8502, Japan
| | - Tsuzumi Hirohashi
- Department of Biological Resource Sciences, Faculty of Agriculture, Saga University, 1 Honjo, Saga, 840-8502, Japan
| | - Shin-Ichi Kawaguchi
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0065, Japan
- Center for Education and Research in Agricultural Innovation, Faculty of Agriculture, Saga University, Karatsu, Saga, 847-0021, Japan
| | - Kavindra K Wijesundera
- Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Peradeniya, 20400, Sri Lanka
| | | | - Kanji Ishimaru
- Department of Biological Resource Sciences, Faculty of Agriculture, Saga University, 1 Honjo, Saga, 840-8502, Japan
| | - Suranga P Kodithuwakku
- Department of Animal Science, Faculty of Agriculture, University of Peradeniya, Peradeniya, 20400, Sri Lanka
- ERA Chair COMBIVET, Institute of veterinary Medicine and Animal Science, Estonian University of Life Science, Tartu, 51014, Estonia
| | - Tadayuki Tsujita
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, 890-0065, Japan
- Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University, Saga, 840-8502, Japan
| |
Collapse
|
|
16
|
Qiu S, Zorig A, Sato N, Yanagihara A, Kanazawa T, Takasugi M, Arai H. Effect of Polyphenols in Sea Buckthorn Berry on Chemical Mediator Release from Mast Cells. Prev Nutr Food Sci 2023; 28:335-346. [PMID: 37842252 PMCID: PMC10567591 DOI: 10.3746/pnf.2023.28.3.335] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/23/2023] [Accepted: 06/01/2023] [Indexed: 10/17/2023] Open
Abstract
Sea buckthorn (Hippophae rhamnoides L.) is a deciduous shrub of the Elaeagnaceae family and is widely distributed in northern Eurasia. Sea buckthorn berry (SBB) has attracted attention for its use in many health foods, although its physiological function remains unknown. In this study, we investigated the inhibitory effect of SBB extract and its fractions on Type-I allergy using mast cell lines. Among these fractions, SBB fraction with the highest amount of antioxidant polyphenols significantly inhibited the release of chemical mediators such as histamine and leukotriene B4 (LTB4) from the stimulated mast cells. This fraction also inhibited the influx of calcium ions (Ca2+) and the phosphorylation of tyrosine residues in proteins, including spleen tyrosine kinase, which is associated with signal transduction during the release of chemical mediators. The active SBB fraction contained isorhamnetin as its major flavonol aglycon. Isorhamnetin inhibited histamine and LTB4 release from the stimulated cells and suppressed intracellular Ca2+ influx. These results indicate that isorhamnetin is the primary substance responsible for the antiallergic activity in SBB. In conclusion, SBB may alleviate Type-I allergy by inhibiting the release of chemical mediators from mast cells, and polyphenols may contribute to this effect.
Collapse
Affiliation(s)
- Shiman Qiu
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| | - Anuu Zorig
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| | - Naoko Sato
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| | - Ai Yanagihara
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| | - Tsutomu Kanazawa
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| | - Mikako Takasugi
- Department of Life Science, Kyushu Sangyo University, Fukuoka 813-8503, Japan
| | - Hirofumi Arai
- School of Regional Innovation and Social Design Engineering, Kitami Institute of Technology, Kitami 090-8507, Japan
| |
Collapse
|
|
17
|
Machado IF, Miranda RG, Dorta DJ, Rolo AP, Palmeira CM. Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases. Antioxidants (Basel) 2023; 12:1212. [PMID: 37371941 DOI: 10.3390/antiox12061212] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 06/29/2023] Open
Abstract
Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation and antioxidant defenses results in the overproduction of ROS and subsequent oxidative damage to biomolecules and cellular components that disturb cellular function. Oxidative stress contributes to the initiation and progression of many liver pathologies such as ischemia-reperfusion injury (LIRI), non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Therefore, controlling ROS production is an attractive therapeutic strategy in relation to their treatment. In recent years, increasing evidence has supported the therapeutic effects of polyphenols on liver injury via the regulation of ROS levels. In the current review, we summarize the effects of polyphenols, such as quercetin, resveratrol, and curcumin, on oxidative damage during conditions that induce liver injury, such as LIRI, NAFLD, and HCC.
Collapse
Affiliation(s)
- Ivo F Machado
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- IIIUC-Institute of Interdisciplinary Research, University of Coimbra, 3000 Coimbra, Portugal
| | - Raul G Miranda
- School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, São Paulo 14040, Brazil
| | - Daniel J Dorta
- Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040, Brazil
| | - Anabela P Rolo
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal
| | - Carlos M Palmeira
- CNC-Center for Neuroscience and Cell Biology, CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3000 Coimbra, Portugal
- Department of Life Sciences, University of Coimbra, 3000 Coimbra, Portugal
| |
Collapse
|
|
18
|
Bhuia MS, Wilairatana P, Chowdhury R, Rakib AI, Kamli H, Shaikh A, Coutinho HDM, Islam MT. Anticancer Potentials of the Lignan Magnolin: A Systematic Review. Molecules 2023; 28:3671. [PMID: 37175081 PMCID: PMC10180476 DOI: 10.3390/molecules28093671] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.
Collapse
Affiliation(s)
- Md. Shimul Bhuia
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.)
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Raihan Chowdhury
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.)
| | - Asraful Islam Rakib
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.)
| | - Hossam Kamli
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Ahmad Shaikh
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Henrique D. M. Coutinho
- Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil
| | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; (M.S.B.)
| |
Collapse
|
|
19
|
Dawoud MHS, Zaafan MA, Saleh SS, Mannaa IM, Sweed NM. Response surface optimization of a cardioprotective compound through pharmacosomal drug delivery system: in vivo bioavailability and cardioprotective activity potential. Drug Deliv Transl Res 2023:10.1007/s13346-023-01315-w. [PMID: 37017879 PMCID: PMC10382421 DOI: 10.1007/s13346-023-01315-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2023] [Indexed: 04/06/2023]
Abstract
Vanillic acid (VA) is a phenolic compound with potential antioxidant activity, which improves ischemia-induced myocardial degeneration, by reducing oxidative stress; however, it suffers poor bioavailability owing to its poor solubility. VA-loaded pharmacosomes were optimized using a central composite design, where the effect of phosphatidylcholine:VA molar ratio and the precursor concentration were studied. An optimized formulation (O1) was prepared and tested for the release rate of VA, in vivo bioavailability, and cardioprotective potential on myocardial infarction-induced rats. The optimized formulation showed a particle size of 229.7 nm, polydispersity index of 0.29, and zeta potential of - 30 mV. O1 showed a sustained drug release for 48 h. The HPLC-UV method was developed for the determination of VA in plasma samples using protein precipitation. The optimized formulation showed a great improvement in the bioavailability as compared to VA. The residence time of the optimized formula was 3 times longer than VA. The optimized formulation showed a more potent cardioprotective effect as compared to VA, via inhibition of the MAPK pathway with subsequent inhibition of PI3k/NF-κB signaling, in addition to its antioxidant effect. The optimized formulation showed normalization of many oxidative stress and inflammatory biomarkers. Thus, a VA-loaded pharmacosome formulation with promising bioavailability and cardioprotective activity potential was prepared.
Collapse
Affiliation(s)
- Marwa H S Dawoud
- Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October City, Egypt.
| | - Mai A Zaafan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October City, Egypt
| | - Sarah S Saleh
- Department of Analytical Chemistry, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October City, Egypt
| | - Islam M Mannaa
- Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October City, Egypt
| | - Nabila M Sweed
- Department of Pharmaceutics, Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th of October City, Egypt
| |
Collapse
|
|
20
|
Yehia RS, Altwaim SA. An Insight into In Vitro Antioxidant, Antimicrobial, Cytotoxic, and Apoptosis Induction Potential of Mangiferin, a Bioactive Compound Derived from Mangifera indica. PLANTS (BASEL, SWITZERLAND) 2023; 12:1539. [PMID: 37050165 PMCID: PMC10096949 DOI: 10.3390/plants12071539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 03/25/2023] [Accepted: 03/28/2023] [Indexed: 06/19/2023]
Abstract
Due to their low cost, toxicity, and health risks, medicinal plants have come to be seen as useful products and sources of biologically active compounds. Mangifera indica L., a medicinal plant with a long history, has a high bioactive metabolites content. Mangiferin (C19H18O11) is primary isolated from M. indica's leaves, which has many pharmacological benefits. In this investigation, ultrasonic-assisted extraction with ethanol as the extraction solvent was applied to obtain mangiferin from a local type of M. indica leaves. HPLC was performed after a dichloromethane-ethyl acetate liquid-liquid fractionation method. Further, UV-vis, FTIR, and NMR spectroscopy were utilized to elucidate the structure. Interestingly, purified mangiferin displayed promising antimicrobial efficacy against a diverse variety of fungal and bacterial pathogens with MICs of 1.95-62.5 and 1.95-31.25 µg/mL, respectively. Time-kill patterns also showed that mangiferin had both bactericidal and fungicidal action. Furthermore, it exhibited strong radical dosage-dependent scavenging activity (IC50 = 17.6 μg/mL) compared to vitamin C (Vc, IC50 = 11.9 μg/mL), suggesting it could be developed into a viable antioxidant agent. To our delight, the IC50 values of mangiferin for the MCF-7 and HeLa cell lines were 41.2 and 44.7 μg/mL, respectively, from MTT cell viability testing, and it was less harmful when tested against the noncancerous cell line. Notably, it significantly induced cell apoptosis in MCF-7 cells by 62.2-83.4% using annexin V-FITC/PI labeling. Hence, our findings suggest that mangiferin can be used in the medical industry to create therapeutic interventions and medication delivery systems for society.
Collapse
Affiliation(s)
- Ramy S. Yehia
- Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza 12613, Egypt
| | - Sarah A. Altwaim
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 22252, Saudi Arabia
| |
Collapse
|
|
21
|
Ayenew KD, Wasihun Y. Hepatoprotective effect of methanol extract of Agave americana leaves on paracetamol induced hepatotoxicity in Wistar albino rats. BMC Complement Med Ther 2023; 23:99. [PMID: 37005601 PMCID: PMC10067186 DOI: 10.1186/s12906-023-03931-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 03/21/2023] [Indexed: 04/04/2023] Open
Abstract
BACKGROUND Ethiopians locally treat liver illnesses with A. Americana. Available literature demonstrates this. However, there are few in-vivo investigations that provide supporting data. The aim of this study was to evaluate the hepatoprotective effects of methanolic extract of Agave americana leaves on rat liver damage caused by paracetamol. METHODS The acute oral toxicity test was conducted in accordance with OECD-425 recommendations. The approach outlined by Eesha et al. (Asian Pac J Trop Biomed 4:466-469, 2011) was used to test the hepatoprotective activity. Wistar male rats weighing between 180 and 200 g were used, and six groups with seven animals each were formed. Group I received treatment with gum acacia (2%) at a dose of 2 ml/kg p.o. daily for 7 days. Rats in group II were treated with 2% gum acacia orally daily for seven days along with a single dose of paracetamol (2 mg/kg) p.o. on 7th day. Silymarin (50 mg/kg) was given orally to Group III for 7 days. Plant extract doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg were administered orally to Groups IV -VI for seven days, respectively. All rats in groups III-VI were treated with paracetamol (2 mg/kg) 30 min following extract administration. Blood samples were obtained from the cardiac puncture after paracetamol had been used for 24 h to induce toxicity. Serum biomarkers (AST, ALT, ALP, and total bilirubin) were estimated. A histopathological investigation was also done. RESULTS No toxicity symptoms or animal fatalities were recorded during the acute toxicity study. The values of AST, ALT, ALP, and total bilirubin were all substantially raised by paracetamol. Significant hepatoprotective effects were obtained by pretreatment with A. americana extract. Histopathological examination of the liver tissues of paracetamol control group represented the presence of marked foci of mononuclear infiltration in the hepatic parenchyma tissue, sinusoid, and around central vein, as well as disorganization of hepatic plates, necrosis, and fatty changes of hepatocytes. Pretreatment with A. americana extract reversed these alterations. Results of the methanolic extract of A. americana were comparable to Silymarin. CONCLUSION The current investigation supports the hepatoprotective properties of Agave americana methanolic extract.
Collapse
Affiliation(s)
- Kassahun Dires Ayenew
- Department of Pharmacy, Asrat Woldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia.
| | - Yared Wasihun
- Department of Internal Medicine, Ras Desta Damtew Memorial Hospital, Addis Ababa, Ethiopia
| |
Collapse
|
|
22
|
A Comprehensive Review on Extraction, Structure, Detection, Bioactivity, and Metabolism of Flavonoids from Sea Buckthorn (Hippophae rhamnoides L.). J Food Biochem 2023. [DOI: 10.1155/2023/4839124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Sea buckthorn (Hippophae rhamnoides L.) is an important plant with homology of medicine and food. It has rich nutritional and medicinal properties. It is used as a traditional Chinese medicine with therapeutic functions of invigorating spleen, relieving cough, eliminating food, eliminating phlegm, dispersing blood stasis, and promoting blood circulation. This review comprehensively summarized flavonoids from sea buckthorn (Hippophae rhamnoides L.), including extraction methods (solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, enzyme-assisted extraction, and collaborative extraction), two structure types (18 flavone aglycones and 81 flavone glycosides), detection methods (UV, HPLC, and NMR), bioactivities (antiviral, anti-inflammatory, hepatoprotective, weight-reducing, and hypoglycemic activities), and physiological metabolisms (most of flavonoids are converted into small molecule monophenolic acids through intestinal microbial catabolism). It will supply an important theoretical basis and valuable reference for researching and exploiting sea buckthorn (Hippophae rhamnoides L.) in the future. Practical Applications. Sea buckthorn (Hippophae rhamnoides L.) is an edible and medical plant with many functional properties. A comprehensive review on extraction, structure, detection, bioactivity, and metabolism of flavonoids from sea buckthorn (Hippophae rhamnoides L.) was made in this paper. This review will provide an important foundation for further studies of sea buckthorn (Hippophae rhamnoides L.) focusing on its development and utilization.
Collapse
|
|
23
|
Miao F, Geng S, Ning D. Hydroxytyrosol ameliorates LPS-induced acute liver injury (ALI) in mice by modulating the balance between M1/M2 phenotype macrophage and inhibiting TLR4/NF-κB activation. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023] Open
|
|
24
|
Ahmad F, Nadeem H. Mass Spectroscopy as an Analytical Tool to Harness the Production of Secondary Plant Metabolites: The Way Forward for Drug Discovery. Methods Mol Biol 2023; 2575:77-103. [PMID: 36301472 DOI: 10.1007/978-1-0716-2716-7_5] [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] [Indexed: 06/16/2023]
Abstract
The molecular map of diverse biological molecules linked with structure, function, signaling, and regulation within a cell can be elucidated using an analytically demanding omic approach. The latest trend of using "metabolomics" technologies has explained the natural phenomenon of opening a new avenue to understand and enhance bioactive compounds' production. Examination of sequenced plant genomes has revealed that a considerable portion of these encodes genes of secondary metabolism. In addition to genetic and molecular tools developed in the current era, the ever-increasing knowledge about plant metabolism's biochemistry has initiated an approach for wisely designed, more productive genetic engineering of plant secondary metabolism for improved defense systems and enhanced biosynthesis of beneficial metabolites. Secondary plant metabolites are natural products synthesized by plants that are not directly involved with their average growth and development but play a vital role in plant defense mechanisms. Plant secondary metabolites are classified into four major classes: terpenoids, phenolic compounds, alkaloids, and sulfur-containing compounds. More than 200,000 secondary metabolites are synthesized by plants having a unique and complex structure. Secondary plant metabolites are well characterized and quantified by omics approaches and therefore used by humans in different sectors such as agriculture, pharmaceuticals, chemical industries, and biofuel. The aim is to establish metabolomics as a comprehensive and dynamic model of diverse biological molecules for biomarkers and drug discovery. In this chapter, we aim to illustrate the role of metabolomic technology, precisely liquid chromatography-mass spectrometry, capillary electrophoresis mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy, specifically as a research tool in the production and identification of novel bioactive compounds for drug discovery and to obtain a unified insight of secondary metabolism in plants.
Collapse
Affiliation(s)
- Faheem Ahmad
- Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
| | - Hera Nadeem
- Department of Botany, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| |
Collapse
|
|
25
|
Suh JY, Lee HJ, Sim DY, Park JE, Ahn CH, Park SY, Shin N, Kim B, Shim BS, Kim SH. Hypolipogenic effects of Icariside E4 via phosphorylation of AMPK and inhibition of MID1IP1 in HepG2 cells. Phytother Res 2023; 37:7-14. [PMID: 35916211 DOI: 10.1002/ptr.7584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 06/12/2022] [Accepted: 07/07/2022] [Indexed: 01/19/2023]
Abstract
Though icariside E4 (IE4) is known to have anti-noceptive, anti-oxidant, anti-Alzheimer and anti-inflammatory effects, there was no evidence on the effect of IE4 on lipid metabolism so far. Hence, the hypolipogenic mechanism of IE4 was investigated in HepG2 hepatocellular carcinoma cells (HCCs) in association with MID1 Interacting Protein 1(MID1IP1) and AMPK signaling. Here, IE4 did not show any toxicity in HepG2 cells, but reduced lipid accumulation in HepG2 cells by Oil Red O staining. MID1IP1 depletion decreased the expression of SREBP-1c and fatty acid synthase (FASN) and induced phosphorylation of ACC in HepG2 cells. Indeed, IE4 activated phosphorylation of AMPK and ACC and inhibited the expression of MID1IP1 in HepG2 cells. Furthermore, IE4 suppressed the expression of SREBP-1c, liver X receptor-α (LXR), and FASN for de novo lipogenesis in HepG2 cells. Interestingly, AMPK inhibitor compound C reversed the ability of IE4 to reduce MID1IP1, SREBP-1c, and FASN and activate phosphorylation of AMPK/ACC in HepG2 cells, indicating the important role of AMPK/ACC signaling in IE4-induced hypolipogenic effect. Taken together, these findings suggest that IE4 has hypolipogenic potential in HepG2 cells via activation of AMPK and inhibition of MID1IP1 as a potent candidate for treatment of fatty liver disease.
Collapse
Affiliation(s)
- Jin Young Suh
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Hyo-Jung Lee
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Deok Yong Sim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Ji Eon Park
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Chi-Hoon Ahn
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Su-Yeon Park
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Nari Shin
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Bonglee Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Bum Sang Shim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Sung-Hoon Kim
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| |
Collapse
|
|
26
|
Chilvery S, Yelne A, Khurana A, Saifi MA, Bansod S, Anchi P, Godugu C. Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 108:154510. [PMID: 36332383 DOI: 10.1016/j.phymed.2022.154510] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 08/06/2022] [Accepted: 10/16/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND The liver plays an important role in regulating the metabolic processes and is the most frequently targeted organ by toxic chemicals. Acetaminophen (APAP) is a well-known anti-allergic, anti-pyretic, non-steroidal anti-inflammatory drug (NSAID), which upon overdose leads to hepatotoxicity, the major adverse event of this over-the-counter drug. PURPOSE APAP overdose induced acute liver injury is the second most common cause that often requires liver transplantation worldwide, for which N-acetyl cysteine is the only synthetic drug clinically approved as an antidote. So, it was felt that there is a need for the novel therapeutic approach for the treatment of liver diseases with less adverse effects. This review provides detailed analysis of the different plant extracts; phytochemicals and herbal formulations for the amelioration of APAP-induced liver injury. METHOD The data was collected using different online resources including PubMed, ScienceDirect, Google Scholar, Springer, and Web of Science using keywords given below. RESULTS Over the past decades various reports have revealed that plant-based approaches may be a better treatment choice for the APAP-induced hepatotoxicity in pre-clinical experimental conditions. Moreover, herbal compounds provide several advantages over the synthetic drugs with fewer side effects, easy availability and less cost for the treatment of life-threatening diseases. CONCLUSION The current review summarizes the hepatoprotective effects and therapeutic mechanisms of various plant extracts, active phytoconstituents and herbal formulations with potential application against APAP induced hepatotoxicity as the numbers of hepatoprotective natural products are more without clinical relativity. Further, pre-clinical pharmacological research will contribute to the designing of natural products as medicines with encouraging prospects for clinical application.
Collapse
Affiliation(s)
- Shrilekha Chilvery
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Amit Yelne
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Amit Khurana
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Mohd Aslam Saifi
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Sapana Bansod
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Pratibha Anchi
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
| |
Collapse
|
|
27
|
Mohamed GA, Ibrahim SRM, Hareeri RH, Binmahfouz LS, Bagher AM, Abdallah HM, Elsaed WM, El-Agamy DS. Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis. Nutrients 2022; 15:nu15010016. [PMID: 36615674 PMCID: PMC9824319 DOI: 10.3390/nu15010016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Garcinia mangostana L. (Clusiaceae), a popular tropical fruit for its juiciness and sweetness, is an opulent fountain of prenylated and oxygenated xanthones with a vast array of bio-activities. Garcinone E (GE), a xanthone derivative reported from G. mangostana, possesses cytotoxic and aromatase inhibitory activities. The present research endeavors to investigate the hepato-protection efficaciousness of GE on concanavalin-A (Con-A)-instigated hepatitis. Results showed that GE pretreating noticeably diminishes both the serum indices (transaminases, ALP, LDH, and γ-GT) and histopathological lesions of the liver. It counteracted neutrophil and CD4+ infiltration into the liver. GE furthered the Nrf2 genetic expression and its antioxidants' cascade, which resulted in amelioration of Con-A-caused oxidative stress (OS), lipid per-oxidative markers (4-HNE, MDA, PC) reduction, and intensified antioxidants (TAC, SOD, GSH) in the hepatic tissue. Additionally, GE prohibited NF-ĸB (nuclear factor kappa-B) activation and lessened the genetics and levels of downstream cytokines (IL1β and IL6). Moreover, the TNF-α/JNK axis was repressed in GE-treated mice, which was accompanied by attenuation of Con-A-induced apoptosis. These findings demonstrated the protective potential of GE in Con-A-induced hepatitis which may be associated with Nrf2/HO-1 signaling activation and OS suppression, as well as modulation of the NF-κB and TNF-α/JNK/apoptosis signaling pathway. These results suggest the potential use of GE as a novel hepato-protective agent against autoimmune hepatitis.
Collapse
Affiliation(s)
- Gamal A. Mohamed
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Correspondence: ; Tel.: +966-597636182
| | - Sabrin R. M. Ibrahim
- Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
| | - Rawan H. Hareeri
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Lenah S. Binmahfouz
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Amina M. Bagher
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Hossam M. Abdallah
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Wael M. Elsaed
- Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Dina S. El-Agamy
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| |
Collapse
|
|
28
|
Vijayan N, Perumal MK. A critical review on anti-fibrotic phytochemicals targeting activated hepatic stellate cells. J Food Biochem 2022; 46:e14438. [PMID: 36209494 DOI: 10.1111/jfbc.14438] [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: 07/13/2022] [Revised: 08/29/2022] [Accepted: 09/16/2022] [Indexed: 01/18/2023]
Abstract
Liver fibrosis is a major health concern occurring worldwide. It arises due to prolonged wound healing response of various insults like viral, autoimmune, cholestatic, drug-induced, and metabolic diseases. Currently, there is no clinically approved drug for liver fibrosis treatment. Hepatic stellate cells are the principal liver cells that are activated during liver fibrosis, and targeting these activated cells is an ideal therapeutic strategy. Numerous phytochemicals have been demonstrated in vitro and in vivo treating experimental liver fibrosis; however, none of them have been clinically approved for therapeutic use. This review mainly focuses on such hepatoprotective phytochemicals reported inhibiting major signaling pathways that are dysregulated in activated hepatic stellate cells. PRACTICAL APPLICATIONS: Liver fibrosis is a global health concern and there is no FDA approved drug to treat liver fibrosis. Although notable pharmacological agents like pentoxifylline, gliotoxin, imatinibmesylate, Gleevec, and so on are reported to exhibit anti-fibrotic effect, the major concern is their side effect. Hence, phytochemicals are promising candidates that could be employed against liver fibrosis. In this review, the anti-fibrotic potential of phytochemicals targeting activated HSCs are summarized. Understanding these phytochemicals will further help in the development of agents that are more effective against liver fibrosis.
Collapse
Affiliation(s)
- Nivya Vijayan
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Madan Kumar Perumal
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, India.,Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| |
Collapse
|
|
29
|
Sharma N, Gupta N, Orfali R, Kumar V, Patel CN, Peng J, Perveen S. Evaluation of the Antifungal, Antioxidant, and Anti-Diabetic Potential of the Essential Oil of Curcuma longa Leaves from the North-Western Himalayas by In Vitro and In Silico Analysis. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27227664. [PMID: 36431765 PMCID: PMC9695312 DOI: 10.3390/molecules27227664] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/04/2022] [Accepted: 11/04/2022] [Indexed: 11/09/2022]
Abstract
Essential oils (EOs) have gained immense popularity due to considerable interest in the health, food, and pharmaceutical industries. The present study aimed to evaluate the antimicrobial and antioxidant activity and the anti-diabetic potential of Curcuma longa leaf (CLO) essential oil. Further, major phytocompounds of CLO were analyzed for their in-silico interactions with antifungal, antioxidant, and anti-diabetic proteins. CLO was found to have a strong antifungal activity against the tested Candida species with zone of inhibition (ZOI)-11.5 ± 0.71 mm to 13 ± 1.41 mm and minimum inhibitory concentration (MIC) was 0.63%. CLO also showed antioxidant activity, with IC50 values of 5.85 ± 1.61 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and 32.92 ± 0.64 µM using ferric reducing antioxidant power (FRAP) assay. CLO also showed anti-diabetic activity with an IC50 of 43.06 ± 1.24 µg/mL as compared to metformin (half maximal inhibitory concentration, IC50-16.503 ± 0.66 µg/mL). Gas chromatography-mass spectrometry (GC-MS) analysis of CLO showed the presence of (-)-zingiberene (17.84%); 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene)-(15.31%); cyclohexene, 4-methyl-3-(1-methylethylidene) (12.47%); and (+)-4-Carene (11.89%) as major phytocompounds. Molecular docking of these compounds with antifungal proteins (cytochrome P450 14 alpha-sterol demethylase, PDB ID: 1EA1, and N-myristoyl transferase, PDB ID: 1IYL), antioxidant (human peroxiredoxin 5, PDB ID: 1HD2), and anti-diabetic proteins (human pancreatic alpha-amylase, PDB ID: 1HNY) showed strong binding of 3,7-cyclodecadien-1-one with all the selected protein targets. Furthermore, molecular dynamics (MD) simulations for a 100 ns time scale revealed that most of the key contacts of target proteins were retained throughout the simulation trajectories. Binding free energy calculations using molecular mechanics generalized born surface area (MM/GBSA), and drug-likeness and toxicity analysis also proved the potential for 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene) to replace toxic synthetic drugs and act as natural antioxidants.
Collapse
Affiliation(s)
- Nitin Sharma
- Department of Biotechnology, Chandigarh College of Technology, CGC, Landran, Mohali 140307, India
- Correspondence: (N.S.); (S.P.)
| | - Nidhi Gupta
- Department of Biotechnology, Chandigarh College of Technology, CGC, Landran, Mohali 140307, India
| | - Raha Orfali
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Vikas Kumar
- University Institute of Biotechnology, Chandigarh University, Gharuan, Mohali 140413, India
| | - Chirag N. Patel
- Department of Botany, Bioinformatics, and Climatic Change Impacts Management, School of Sciences, Gujarat University, Ahmedabad 380009, India
| | - Jiangnan Peng
- Department of Medicinal, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA
| | - Shagufta Perveen
- Department of Medicinal, School of Computer, Mathematical and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA
- Correspondence: (N.S.); (S.P.)
| |
Collapse
|
|
30
|
Gasparotto Junior A, Lívero FADR, Acco A. Editorial: Biologically active products as therapeutic options for the treatment of cardiovascular diseases related to liver injury. Front Pharmacol 2022; 13:1041020. [DOI: 10.3389/fphar.2022.1041020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 10/14/2022] [Indexed: 11/13/2022] Open
|
|
31
|
Ameliorative Impacts of Wheat Germ Oil against Ethanol-Induced Hepatic and Renal Dysfunction in Rats: Involvement of Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Signaling Pathways. LIFE (BASEL, SWITZERLAND) 2022; 12:life12101671. [PMID: 36295108 PMCID: PMC9605469 DOI: 10.3390/life12101671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 11/07/2022]
Abstract
Wheat germ oil (WGO) is a well-known product with anti-inflammatory and antioxidant properties. The current study aimed to investigate the impacts of WGO against ethanol-induced liver and kidney dysfunction at the serum, anti-inflammatory, antioxidants and anti-apoptotic signaling pathways. Rats received saline orally as a negative control or WGO in a dose of 1.5 mL/kg (1400 mg/kg body weight orally) for 15 days. The affected group received ethanol 50% v/v 10 mL/kg (5 g/kg) body weight orally once a day for consecutive 15 days to induce hepatorenal injuries in ethanolic non-treated group. The protective group received WGO daily 1 h before ethanol administration. Serum (1.5 mL) from blood was extracted and examined for the changes in biochemical assessments in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, serum γ-glutamyl transpeptidase (GGT), total protein, serum albumin, butyrylcholinesterase (BChE), total cholesterol (TC), total triglyceride (TG), urea, creatinine, uric acid, potassium (K+), Beta-2 microglobulin (β2M), malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and aspartate aminotransferase (AST). Kidney and liver homogenate was used to measure MDA, GSH and catalase activities. Quantitative real time PCR (qRT-PCR) was used to express Nrf2 and HO-1 in liver, and NF-kB and kidney injury molecule (KIM-1) in kidneys, which are correlated with oxidative stress and inflammation. Capase-3 and Bcl2 genes were examined using immunohistochemical analysis in the kidney and liver. Ethanol administration induced significant alteration in examined liver and kidney markers (AST, ALT, GGT, ALP, total proteins, urea, creatinine and uric acid). Moreover, alcohol administration decreased antioxidant activities at serum and hepatorenal tissues (GSH, catalase and SOD), while MDA was increased as a tissue degradation marker. Inflammatory cytokines, together with genes of oxidative stress markers (Nrf2 and HO-1), were all affected. At cellular levels, apoptotic marker caspase-3 was upregulated, while antiapoptotic marker B-cell lymphoma 2 (Bcl2), was down regulated using immunohistochemical analysis. Of interest, pretreatment with WGO improved the side effects induced by ethanol on hepatic, renal biomarkers and reversed its impact on serum and tissue antioxidant parameters. Nrf2/HO-1 were upregulated, while NFk-B and KIM-1 were downregulated using real time PCR. Immune reactivities of caspase-3 and Bcl2 genes were restored in the protective group. In conclusion, WGO ameliorated ethanol-induced hepatic and renal dysfunction at the biochemical, molecular and cellular levels by regulating some mechanisms that controls oxidative stress, apoptosis, inflammation and anti-apoptotic pathways.
Collapse
|
|
32
|
Tamarix articulata Induced Prevention of Hepatotoxicity Effects of In Vivo Carbon Tetrachloride by Modulating Pro-Inflammatory Serum and Antioxidant Enzymes to Reverse the Liver Fibrosis. Antioxidants (Basel) 2022; 11:antiox11091824. [PMID: 36139897 PMCID: PMC9496017 DOI: 10.3390/antiox11091824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 08/29/2022] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels.
Collapse
|
|
33
|
Li M, Chen L, Zhao Y, Sun H, Zhao L. Research on the Mechanism of HRP Relieving IPEC-J2 Cells Immunological Stress Based on Transcriptome Sequencing Analysis. Front Nutr 2022; 9:944390. [PMID: 35911118 PMCID: PMC9336541 DOI: 10.3389/fnut.2022.944390] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 06/13/2022] [Indexed: 11/27/2022] Open
Abstract
Early weaning increased the economic benefits of piglets. However, early weaning damages the intestinal barrier of piglets and causes immunological stress. The mechanism by which Hippophae rhamnoides polysaccharide (HRP) alleviates lipopolysaccharide (LPS)-induced intestinal porcine epithelial cells (IPEC-J2) inflammatory damage was investigated using proteomics in our previous studies. In this study we employed RNA-sequencing (RNA-seq) to determine the level and function of differentially expressed genes (DEGs) and further explore the mechanism of the HRP anti-inflammatory and immune process. The differential expression analysis indicated that 3622, 1216, and 2100 DEGs in the IPEC-J2 cells were identified in C vs. L, L vs. H6-L, and C vs. H6-L, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis foundsix identified pathways related to the immune system. Additionally, we used the Science, Technology, Engineering, and Math (STEM) program to categorize the 3,134 DEGs that were differentially expressed in H2-L, H4-L and H6-L into eight possible expression profiles, in which 612 were clustered into two profiles. The accuracy and consistency of RNA-seq data were validated by the results of qRT-PCR of the nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), MAP kinase interacting serine/threonine kinase 2 (MKNK2), mitogen-activated protein kinase kinase 1 (MAP2K1), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), Ras-related protein R-Ras (RRAS), TNF receptor-associated factor 1 (TRAF1), NF-kappa-B inhibitor alpha (NFKBIA), interleukin 8 (IL8), tumor necrosis factor, alpha-induced protein 3 (TNFAIP3), and transforming growth factor beta-1 (TGFB1). Transcriptome sequencing also indicated that HRP reduced the expression levels of related DEGs and inhibited the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway. Our findings indicate that the application of HRP in piglet diets during the early weaning period can improve intestinal epithelial function and integrity, and relieve intestinal damage, and improve piglet health.
Collapse
Affiliation(s)
- Muyang Li
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Lu Chen
- Shanxi Animal Husbandry and Veterinary School, Taiyuan, China
| | - Yiran Zhao
- College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Hui Sun
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
- *Correspondence: Lei Zhao
| | - Lei Zhao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Hui Sun
| |
Collapse
|
|
34
|
Phytochemical Analysis and Antioxidant and Antidiabetic Activities of Extracts from Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica. Adv Pharmacol Pharm Sci 2022; 2022:4929824. [PMID: 35845257 PMCID: PMC9283070 DOI: 10.1155/2022/4929824] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/28/2022] [Accepted: 06/17/2022] [Indexed: 01/26/2023] Open
Abstract
Diabetes is a metabolic disorder of high blood sugar levels which leads to various chronic health-related complications. The digestive enzymes α-amylase and α-glucosidase play a major role in the hydrolysis of starch to glucose; hence, inhibiting these enzymes is considered an important strategy for the treatment of diabetes. Medicinal plants such as Bergenia ciliata, Mimosa pudica, and Phyllanthus emblica are commonly used in traditional remedies due to their numerous health benefits. This study aimed to determine the phytochemicals as well as TPC and TFC contents in these plant extracts along with their antioxidant and enzyme inhibitory activity against α-glucosidase and α-amylase. The ethyl acetate extracts of selected plants have shown higher TPC and TFC contents. The aqueous extract of B. ciliata (IC50: 16.99 ± 2.56 μg/mL) and ethyl acetate extract of P. emblica (IC50: 11.98 ± 0.36 μg/mL) and M. pudica (IC50: 21.39 ± 3.76 μg/mL) showed effective antioxidant activities. Furthermore, ethyl acetate extract of B. ciliata showed significant inhibitory activity against α-amylase and α-glucosidase with IC50 values of 38.50 ± 1.32 μg/mL and 3.41 ± 0.04 μg/mL, respectively. Thus, secondary metabolites of these medicinal plants can be repurposed as effective inhibitors of digestive enzymes.
Collapse
|
|
35
|
Hashmat Z, Channa IS, Safdar M, Ozaslan M, Saeed M, Siddique F, Junejo Y. Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene. Toxicol Res 2022; 38:323-330. [PMID: 35874506 PMCID: PMC9247125 DOI: 10.1007/s43188-021-00116-y] [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: 04/19/2021] [Revised: 11/17/2021] [Accepted: 11/20/2021] [Indexed: 10/19/2022] Open
Abstract
Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic blocker) in APAP-induced acute liver injury in an animal model using New Zealand rabbits. APAP (1 g/kg of body weight) was given to New Zealand rabbits either with or without terazosin (0.5 mg/kg) and serum was collected after 4 h. Serum alanine transaminase (ALT), alkaline phosphatase (ALP) and ferritin level were determined to analyze the liver functioning of treated rabbits. Furthermore, total cholesterol (TC), total lipids (TL), high-density lipoproteins (HDL), low-density lipoprotein (LDL) and triglycerides (TG) levels were estimated to find any change in lipid profile of the treated animals. Moreover, the urea and creatinine levels assayed the actual renal functionality. To identify any modification in gene expression, qPCR of cytochrome P2E1 (CYP2E1) was performed. Terazosin in combination with APAP enhanced liver functioning by reducing the levels of liver injury markers viz. ALP and ALT, while lipid profile was also lowered by down regulation of TC, TL, LDL and TG with enhanced HDL levels. It caused significant down regulation of expression level of CYP2E1. It is concluded that terazosin has better effects induced on the recovery of normal liver functioning, by improving the liver profile, lipid profile and renal functioning both at tissue and molecular levels.
Collapse
Affiliation(s)
- Zoya Hashmat
- Department of Molecular Biology, Virtual University of Pakistan, Karachi, Pakistan
| | - Iffat Saeed Channa
- Department of Molecular Biology, Virtual University of Pakistan, Karachi, Pakistan
- Health Education Officer, Shaheed Benazirabad, Government of Sindh, Nawabshah, Sindh, Pakistan
| | - Muhammad Safdar
- Division of Molecular Biology and Genetics, Deparment of Biology, Gaziantep University, Gaziantep, 27000 Turkey
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100 Pakistan
| | - Mehmet Ozaslan
- Division of Molecular Biology and Genetics, Deparment of Biology, Gaziantep University, Gaziantep, 27000 Turkey
| | - Muhammad Saeed
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100 Pakistan
| | - Faisal Siddique
- Derpartment of Microbiology, Cholistan University of Veterinary & Animal Sciences, Bahawalpur, 63100 Pakistan
| | - Yasmeen Junejo
- Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100 Pakistan
| |
Collapse
|
|
36
|
Ren L, Ma XL, Wang HL, Li R, Cui JJ, Yan PJ, Wang YN, Yu XY, Du P, Yu HY, Guo HH, Tang R, Che YS, Zheng WS, Jiang JD, Wang LL. Prebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis. J Control Release 2022; 348:825-840. [PMID: 35752255 DOI: 10.1016/j.jconrel.2022.06.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/11/2022] [Accepted: 06/17/2022] [Indexed: 11/17/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-β-cyclodextrin inclusion (SHβCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-β-CD. The solubility of SLN was increased by generating SHβCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHβCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHβCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHβCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HβCD on drug absorption and gut microbial homeostasis.
Collapse
Affiliation(s)
- Ling Ren
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Xiao-Lei Ma
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Hong-Liang Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Rui Li
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Jin-Jin Cui
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Peng-Ju Yan
- JiaMuSi University, Heilongjiang 154007, China
| | - Ya-Nan Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Xiao-You Yu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Peng Du
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Hao-Yang Yu
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Hui-Hui Guo
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Rou Tang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Yong-Sheng Che
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
| | - Wen-Sheng Zheng
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
| | - Jian-Dong Jiang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
| | - Lu-Lu Wang
- Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
| |
Collapse
|
|
37
|
ABDALLAH L, SURAKJI I, QAWASME T, AYYASH D, SHHADEH R, OMAR G, BARAKAT A. <i>In Vitro</i> Activity of Some Medicinal Plants on Blood Coagulation. Turk J Pharm Sci 2022; 19:330-335. [DOI: 10.4274/tjps.galenos.2021.14603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
|
|
38
|
Moharana M, Pattanayak SK, Khan F. Identification of phytochemicals from Eclipta alba and assess their potentiality against Hepatitis C virus envelope glycoprotein: virtual screening, docking, and molecular dynamics simulation study. J Biomol Struct Dyn 2022:1-17. [PMID: 35694813 DOI: 10.1080/07391102.2022.2085804] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Hepatitis C virus has a major role in spreading chronic liver disease and hepatocellular carcinoma. Factors such as high costs, pharmacological side effects, and the development of drug resistance strains require the development of new and potentially effective antiviral to treat the various stages of Hepatitis C. Bioactive chemicals have been extracted from medicinal plants and are utilized by humans for the goal of maintaining a healthy lifestyle. The goal of this work is to recognize phytochemicals from Eclipta alba and assess their potentiality activity against the hepatitis C virus envelope glycoprotein using in silico approaches. Phytochemicals from Eclipta alba were virtually screened by Auto dock raccoon and 12 compounds were selected for molecular docking to probe the active binding site. The top two compounds based on the binding score like ecliptalbine and oleanolic acid with HCV E2 glycoprotein exhibit binding energy -8.88 and -8.02 kcal/mol, respectively. The chemicals' usefulness was reinforced by positive pharmacokinetic data. The phytocompounds were identified as potent HCV inhibitors based on the drug likeness and ADMET properties. Both ecliptalbine and oleanolic acid underwent molecular dynamics simulations to determine features such as RMSD, RMSF, SASA, hydrogen-bond number, and MM-PBSA-based binding free energy. From the molecular docking and molecular dynamics simulation study revealed that oleanolic acid obtained from Eclipta alba can be used as inhibitors against Hepatitis C. The identified inhibitor from our study will be study in vitro and in vivo studies to check their efficacy against Hepatitis C.Communicated by Ramaswamy H. Sarma.
Collapse
Affiliation(s)
- Maheswata Moharana
- Department of Chemistry, National Institute of Technology, Raipur, India
| | | | - Fahmida Khan
- Department of Chemistry, National Institute of Technology, Raipur, India
| |
Collapse
|
|
39
|
Yusuf H, Fahriani M, Murzalina C, Mawaddah RD. Inhibitory effects on HepG2 cell proliferation and induction of cell cycle arrest by Chromolaena odorata leaf extract and fractions. PHARMACIA 2022. [DOI: 10.3897/pharmacia.69.e80498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Concern about the side effects of liver cancer treatment has driven studies on anticancer to find compounds from plants that can act as chemotherapy. The anticancer activity of Chromolaena odorata against colorectal cancer, lung cancer, leukemia, cervical cancer, breast cancer, and liver cancer has been proven. However, this plant’s mechanism that can inhibit liver cancer cell growth is still undetermined. This study aims to investigate the anticancer activity of C. odorata against HepG2 cells. Extraction of C. odorata leaves was done by maceration method using 80% ethanol and further fractionated. Total flavonoid and major compound of the crude extract were determined by aluminum chloride colorimetric assay and Liquid Chromatography-Mass Spectrometry method. The IC50 and proliferation analysis was performed by MTT assay. Cell cycle was analyzed by using flowcytometry. Total flavonoid of 1.95% and compounds such as 5,7,8,3ʹ,4ʹ-Pentamethoxyflavonone, 1-Carboethoxy-β-carboline, 3-Methylcanthin-2, 6- dion, Canthin-6-one were found in C. odorata. The proliferation of HepG2 was significantly lower after 72 hours of incubation with ½ IC50 of C. odorata fractions. HepG2 cells treated with C. odorata extract and fractions were accumulated in the G0-G1 phase. These results indicated that C. odorata leaves could inhibit the proliferation of HepG2 cells and induce cell cycle arrest.
Collapse
|
|
40
|
Wang YP, Wang YD, Liu YP, Cao JX, Yang ML, Wang YF, Khan A, Zhao TR, Cheng GG. 6'- O-Caffeoylarbutin from Que Zui tea ameliorates acetaminophen-induced liver injury via enhancing antioxidant ability and regulating the PI3K signaling pathway. Food Funct 2022; 13:5299-5316. [PMID: 35441652 DOI: 10.1039/d2fo00507g] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Que Zui tea (QT), a traditional herbal tea in China, has a significant hepatoprotective effect. 6'-O-Caffeoylarbutin (CA) is the most abundant chemical compound in the QT. However, the hepatoprotective effect of CA has not been investigated. This study is aimed to evaluate the protective effect of CA on acetaminophen (APAP) induced hepatotoxicity in vivo and in vitro and its possible underlying mechanism. In APAP-induced HepG-2 cells, CA inhibited intracellular ROS accumulation and cell apoptosis, and improved the expression of antioxidants including SOD, CAT and GSH. In APAP-administrated mice, CA pretreatment remarkably ameliorated the histopathological damage and inflammatory response, and antioxidant enzyme activity in the serum and liver tissues. Moreover, the immunohistochemistry and immunofluorescence assay results revealed that the CA markedly reduced ROS production and apoptosis, and activated antioxidant transcription factor Nrf2 in the liver. Meanwhile, molecular docking results showed that the strong binding force of CA and PI3K was due to the higher number of hydrogen- and π-bonds with active site residues. Notably, CA pretreatment significantly regulated the expression of PI3K, Akt, Nrf2, NQO1, HO-1, Bcl-2, Bax, caspase-3, and caspase-9 proteins in APAP-treated liver tissues. These data demonstrated that CA had a protective effect against APAP-induced hepatotoxicity via regulating the PI3K/Akt and Nrf2 signaling pathway.
Collapse
Affiliation(s)
- Yong-Peng Wang
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Yu-Dan Wang
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China. .,National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials, Yunnan Minzu University, Kunming, 650500, China
| | - Ya-Ping Liu
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Jian-Xin Cao
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Mei-Lian Yang
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Yi-Fen Wang
- Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
| | - Afsar Khan
- Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan
| | - Tian-Rui Zhao
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| | - Gui-Guang Cheng
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
| |
Collapse
|
|
41
|
Li M, Xie F, Wang L, Zhu G, Qi LW, Jiang S. Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms. Front Pharmacol 2022; 13:857956. [PMID: 35444532 PMCID: PMC9013942 DOI: 10.3389/fphar.2022.857956] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 02/21/2022] [Indexed: 12/15/2022] Open
Abstract
The liver plays an important role in glucose and lipid homeostasis, drug metabolism, and bile synthesis. Metabolic disorder and inflammation synergistically contribute to the pathogenesis of numerous liver diseases, such as metabolic-associated fatty liver disease (MAFLD), liver injury, and liver cancer. Celastrol, a triterpene derived from Tripterygium wilfordii Hook.f., has been extensively studied in metabolic and inflammatory diseases during the last several decades. Here we comprehensively review the pharmacological activities and the underlying mechanisms of celastrol in the prevention and treatment of liver diseases including MAFLD, liver injury, and liver cancer. In addition, we also discuss the importance of novel methodologies and perspectives for the drug development of celastrol. Although celastrol has been claimed as a promising agent against several metabolic diseases, both preclinical and clinical studies are highly required to accelerate the clinical transformation of celastrol in treating different liver illness. It is foreseeable that celastrol-derived therapeutics is evolving in the field of liver ailments.
Collapse
Affiliation(s)
- Mengzhen Li
- Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, China
| | - Faren Xie
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Lu Wang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Guoxue Zhu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Lian-Wen Qi
- Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, China
| | - Shujun Jiang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| |
Collapse
|
|
42
|
Tang D, Zhang Q, Duan H, Ye X, Liu J, Peng W, Wu C. Polydatin: A Critical Promising Natural Agent for Liver Protection via Antioxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9218738. [PMID: 35186191 PMCID: PMC8853764 DOI: 10.1155/2022/9218738] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 01/18/2022] [Indexed: 12/11/2022]
Abstract
Polydatin, one of the natural active small molecules, was commonly applied in protecting and treating liver disorders in preclinical studies. Oxidative stress plays vital roles in liver injury caused by various factors, such as alcohol, viral infections, dietary components, drugs, and other chemical reagents. It is reported that oxidative stress might be one of the main reasons in the progressive development of alcohol liver diseases (ALDs), nonalcoholic liver diseases (NAFLDs), liver injury, fibrosis, hepatic failure (HF), and hepatocellular carcinoma (HCC). In this paper, we comprehensively summarized the pharmacological effects and potential molecular mechanisms of polydatin for protecting and treating liver disorders via regulation of oxidative stress. According to the previous studies, polydatin is a versatile natural compound and exerts significantly protective and curative effects on oxidative stress-associated liver diseases via various molecular mechanisms, including amelioration of liver function and insulin resistance, inhibition of proinflammatory cytokines, lipid accumulation, endoplasmic reticulum stress and autophagy, regulation of PI3K/Akt/mTOR, and activation of hepatic stellate cells (HSCs), as well as increase of antioxidant enzymes (such as catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), glutathione reductase (GR), and heme oxygenase-1 (HO-1)). In addition, polydatin acts as a free radical scavenger against reactive oxygen species (ROS) by its phenolic and ethylenic bond structure. However, further clinical investigations are still needed to explore the comprehensive molecular mechanisms and confirm the clinical treatment effect of polydatin in liver diseases related to regulation of oxidative stress.
Collapse
Affiliation(s)
- Dandan Tang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Qing Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Huxinyue Duan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Xun Ye
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Jia Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Wei Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| | - Chunjie Wu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China
| |
Collapse
|
|
43
|
Al-Najjar BO, Saqallah FG, Abbas MA, Al-Hijazeen SZ, Sibai OA. P2Y 12 antagonists: Approved drugs, potential naturally isolated and synthesised compounds, and related in-silico studies. Eur J Med Chem 2022; 227:113924. [PMID: 34731765 DOI: 10.1016/j.ejmech.2021.113924] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 09/27/2021] [Accepted: 10/13/2021] [Indexed: 12/12/2022]
Abstract
P2Y12 is a platelet surface protein which is responsible for the amplification of P2Y1 response. It plays a crucial role in platelet aggregation and thrombus formation through an ADP-induced platelet activation mechanism. Despite that P2Y12 platelets' receptor is an excellent target for developing antiplatelet agents, only five approved medications are currently in clinical use which are classified into thienopyridines and nucleoside-nucleotide derivatives. In the past years, many attempts for developing new candidates as P2Y12 inhibitors have been made. This review highlights the importance and the role of P2Y12 receptor as part of the coagulation cascade, its reported congenital defects, and the type of assays which are used to verify and measure its activity. Furthermore, an overview is given of the clinically approved medications, the potential naturally isolated inhibitors, and the synthesised candidates which were tested either in-vitro, in-vivo and/or clinically. Finally, we outline the in-silico attempts which were carried out using virtual screening, molecular docking and dynamics simulations in efforts of designing novel P2Y12 antagonists. Various phytochemical classes might be considered as a corner stone for the discovery of novel P2Y12 inhibitors, whereas a wide range of ring systems can be deliberated as leading scaffolds in that area synthetically and theoretically.
Collapse
Affiliation(s)
- Belal O Al-Najjar
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, 19328, Amman, Jordan; Pharmacological and Diagnostic Research Lab, Al-Ahliyya Amman University, 19328, Amman, Jordan.
| | - Fadi G Saqallah
- Pharmaceutical Design and Simulation (PhDS) Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Penang, Malaysia
| | - Manal A Abbas
- Pharmacological and Diagnostic Research Lab, Al-Ahliyya Amman University, 19328, Amman, Jordan; Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, 19328, Amman, Jordan
| | | | - Obada A Sibai
- Faculty of Pharmacy, Al-Ahliyya Amman University, 19328, Amman, Jordan
| |
Collapse
|
|
44
|
Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation. Pharmaceuticals (Basel) 2021; 15:ph15010053. [PMID: 35056110 PMCID: PMC8779555 DOI: 10.3390/ph15010053] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/27/2021] [Accepted: 12/30/2021] [Indexed: 12/13/2022] Open
Abstract
Infertility is an emerging health issue worldwide, and female infertility is intimately associated with embryo implantation failure. Embryo implantation is an essential process during the initiation of prenatal development. Recent studies have strongly suggested that autophagy in the endometrium is the most important factor for successful embryo implantation. In addition, several studies have reported the effects of various natural products on infertility improvement via the regulation of embryo implantation, embryo quality, and endometrial receptivity. However, it is unclear whether natural products can improve embryo implantation ability by regulating endometrial autophagy. Therefore, we performed a literature review of studies on endometrial autophagy, embryo implantation, natural products, and female infertility. Based on the information from these studies, this review suggests a new treatment strategy for female infertility by proposing natural products that have been proven to be safe and effective as endometrial autophagy regulators; additionally, we provide a comprehensive understanding of the relationship between the regulation of endometrial autophagy by natural products and female infertility, with an emphasis on embryo implantation.
Collapse
|
|
45
|
Paul GK, Mahmud S, Hasan MM, Zaman S, Uddin MS, Saleh MA. Biochemical and in silico study of leaf and bark extracts from Aphanamixis polystachya against common pathogenic bacteria. Saudi J Biol Sci 2021; 28:6592-6605. [PMID: 34764775 PMCID: PMC8568816 DOI: 10.1016/j.sjbs.2021.07.032] [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: 05/05/2021] [Revised: 06/29/2021] [Accepted: 07/08/2021] [Indexed: 11/16/2022] Open
Abstract
Aphanamixis polystachya may be a natural, renewable resource against antibiotic-resistant bacterial infections. The antibacterial activity of A. polystachya leaf and bark extracts was investigated against three antibiotic-resistant bacterial species and one fungus. Methanolic leaf extract showed only limited antibacterial activity but both methanolic and aqueous bark extract showed high antimicrobial activity. In an antioxidant activity test, leaf and bark extracts exhibited 50% free radical scavenging at a concentration of 107.14 ± 3.14 μg/mL and 97.13 ± 3.05 μg/mL, respectively, indicating that bark extracts offer more antioxidative activity than leaf extracts. Bark extracts also showed lower toxicity than leaf extracts. This suggests that bark extracts may offer greater development potential than leaf extracts. The molecular dynamics were also investigated through the simulated exploration of multiple potential interactions to understand the interaction dynamics (root-mean-square deviation, solvent-accessible surface area, radius of gyration, and the hydrogen bonding of chosen compounds to protein targets) and possible mechanisms of inhibition. This molecular modeling of compounds derived from A. polystachya revealed that inhibition may occur by binding to the active sites of the target proteins of the tested bacterial strains. A. polystachya bark extract may be used as a natural source of drugs to control antibiotic-resistant bacteria.
Collapse
Affiliation(s)
| | | | - Md. Mehedi Hasan
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
| | - Shahriar Zaman
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
| | - Md. Salah Uddin
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
| | - Md. Abu Saleh
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh
| |
Collapse
|
|
46
|
Rouf R, Ghosh P, Uzzaman MR, Sarker DK, Zahura FT, Uddin SJ, Muhammad I. Hepatoprotective Plants from Bangladesh: A Biophytochemical Review and Future Prospect. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:1633231. [PMID: 34504532 PMCID: PMC8423546 DOI: 10.1155/2021/1633231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/17/2021] [Indexed: 12/14/2022]
Abstract
Liver diseases are quite prevalant in many densely populated countries, including Bangladesh. The liver and its hepatocytes are targeted by virus and microbes, as well as by chemical environmental toxicants, causing wide-spread disruption of metabolic fuctions of the human body, leading to death from end-stage liver diseases. The aim of this review is to systematically explore and record the potential of Bangladeshi ethnopharmacological plants to treat liver diseases with focus on their sources, constituents, and therapeutic uses, including mechanisms of actions (MoA). A literature survey was carried out using Pubmed, Google Scholar, ScienceDirect, and Scopus databases with articles reported until July, 2020. A total of 88 Bangladeshi hepatoprotective plants (BHPs) belonging to 47 families were listed in this review, including Euphorbiaceae, Cucurbitaceae, and Compositae families contained 20% of plants, while herbs were the most cited (51%) and leaves were the most consumed parts (23%) as surveyed. The effect of BHPs against different hepatotoxins was observed via upregulation of antioxidant systems and inhibition of lipid peroxidation which subsequently reduced the elevated liver biomarkers. Different active constituents, including phenolics, curcuminoids, cucurbitanes, terpenoids, fatty acids, carotenoids, and polysaccharides, have been reported from these plants. The hepatoameliorative effect of these constituents was mainly involved in the reduction of hepatic oxidative stress and inflammation through activation of Nrf2/HO-1 and inhibition of NF-κB signaling pathways. In summary, BHPs represent a valuable resource for hepatoprotective lead therapeutics which may offer new alternatives to treat liver diseases.
Collapse
Affiliation(s)
- Razina Rouf
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Puja Ghosh
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Md. Raihan Uzzaman
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Dipto Kumer Sarker
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Fatima Tuz Zahura
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Shaikh Jamal Uddin
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Ilias Muhammad
- National Center for Natural Products Research, School of Pharmacy, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA
| |
Collapse
|
|
47
|
Gegunde S, Alfonso A, Alvariño R, Pérez-Fuentes N, Botana LM. Anhydroexfoliamycin, a Streptomyces Secondary Metabolite, Mitigates Microglia-Driven Inflammation. ACS Chem Neurosci 2021; 12:2336-2346. [PMID: 34110771 PMCID: PMC8893361 DOI: 10.1021/acschemneuro.1c00033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
![]()
Anhydroexfoliamycin, a secondary
metabolite from Streptomyces, has shown antioxidant
properties in primary cortical neurons reducing
neurodegenerative hallmarks diseases, both in vitro and in vivo models. Activated microglia, in the
central nervous system, plays a crucial role in neuroinflammation
and is associated with neurodegeneration. Therefore, the aim of the
present study was to determine the anti-inflammatory and antioxidant
potential of the anhydroexfoliamycin over microglia BV2 cells. Neuroinflammation
was simulated by incubation of microglia cells in the presence of
lipopolysaccharide to activate proinflammatory transduction pathways.
Moreover, a coculture of neuron SH-SY5Y and microglia BV2 cells was
used to evaluate the neuroprotective properties of the Streptomyces metabolite. When microglia cells were preincubated with anhydroexfoliamycin,
proinflammatory pathways, such as the translocation of the nuclear
factor κB, the phosphorylation of c-Jun N-terminal kinase, and
the inducible nitric oxide synthase expression, were inhibited. In
addition, intracellular reactive oxygen species generation and the
liberation of nitric oxide, interleukin 6, and tumor necrosis factor
α were also decreased. Besides, the Streptomyces-derived compound showed antioxidant properties promoting the translocation
of the factor erythroid 2-related factor 2 and protecting the SH-SY5Y
cells from the neurotoxic mediators released by activated microglia.
The effects of this compound were at the same level as the immunosuppressive
drug cyclosporine A. Therefore, these results indicate that anhydroexfoliamycin
is a promising tool to control microglia-driven inflammation with
therapeutic potential in neuroinflammation.
Collapse
Affiliation(s)
- Sandra Gegunde
- Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- Grupo Investigación Biosdiscovery, IDIS, 15706 Santiago de Compostela, Spain
| | - Amparo Alfonso
- Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- Grupo Investigación Biosdiscovery, IDIS, 15706 Santiago de Compostela, Spain
| | - Rebeca Alvariño
- Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- Grupo Investigación Biosdiscovery, IDIS, 15706 Santiago de Compostela, Spain
| | - Nadia Pérez-Fuentes
- Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- Grupo Investigación Biosdiscovery, IDIS, 15706 Santiago de Compostela, Spain
| | - Luis M. Botana
- Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
- Grupo Investigación Biosdiscovery, IDIS, 15706 Santiago de Compostela, Spain
| |
Collapse
|
|
48
|
Antidiabetic, Antimicrobial, and Molecular Profiling of Selected Medicinal Plants. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:5510099. [PMID: 34040646 PMCID: PMC8121587 DOI: 10.1155/2021/5510099] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 04/13/2021] [Indexed: 12/13/2022]
Abstract
Natural products have been the center of attraction ever since they were discovered. Among them, plant-based natural products were popular as analgesics, anti-inflammatory, antidiabetic, and cosmetics and possess widespread biotechnological applications. The use of plant products as cosmetics and therapeutics is deep-rooted in Nepalese society. Although there are few ethnobotanical studies conducted, extensive research of these valuable medicinal plants has not been a priority due to the limitation of technology and infrastructure. Here, we selected 4 traditionally used medicinal plants to examine their bioactive properties and their enzyme inhibition potential. α-Glucosidase and α-amylase inhibitory activities were investigated using an in vitro model followed up by antioxidant and antimicrobial activities. The present study shows that ethyl acetate fraction of Melastoma melabathrium (IC50 9.1 ± 0.3 µg/mL) and water fraction Acacia catechu (IC50 9.0 ± 0.6 µg/mL) exhibit strong α-glucosidase inhibition. Likewise, the highest α-amylase inhibition was shown by crude extracts of Ficus religiosa (IC50 29.2 ± 1.2 µg/mL) and ethyl acetate fractions of Shorea robusta (IC50 69.3 ± 1.1 µg/mL), and the highest radical scavenging activity was shown by F. religiosa with an IC50 67.4 ± 0.6 µg/mL. Furthermore, to identify the metabolites within the fractions, we employed high-resolution mass spectrometry (LC-HRMS) and annotated 17 known metabolites which justify our assumption on activity. Of 4 medicinal plants examined, ethyl acetate fraction of S. robusta, ethyl acetate fraction of M. melabathrium, and water or ethyl acetate fraction of A. catechu extracts illustrated the best activities. With our study, we set up a foundation that provides authentic evidence to the community for use of these traditional plants. The annotated metabolites in this study support earlier experimental evidence towards the inhibition of enzymes. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of diabetes and pathogens.
Collapse
|
|
49
|
Long L, Yang Y, Zhu T, Zhang X, Qi S, Liu T, Song K, Wang D, Gao H. New pentacyclic triterpenoids isolated from Leptopus chinensis and their hepatoprotective activities on tert-butyl hydroperoxide-induced oxidative injury. RSC Adv 2021; 11:12784-12793. [PMID: 35423795 PMCID: PMC8697041 DOI: 10.1039/d1ra00962a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 03/08/2021] [Indexed: 12/25/2022] Open
Abstract
Eight unknown pentacyclic triterpenoids (1-4 and 8-11), along with eight known analogues (5-7 and 12-16) have been first isolated from the dried whole plant of Leptopus chinensis. The structures of the new compounds were determined by comprehensive spectroscopic methods, including 1D and 2D NMR, as well as HRESIMS measurements. Meanwhile, the hepatoprotective activities of the isolated compounds were preliminarily evaluated, and the results indicated that compounds 2, 5 and 16 possess potent protective effects on tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in vitro, and further study revealed that 16 significantly alleviates t-BHP-induced hepatotoxicity by effectively improving cell viability and decreasing reactive oxygen species (ROS) generation and the cell apoptosis rate in HepG2 cells.
Collapse
Affiliation(s)
- Liping Long
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Ye Yang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Tianliang Zhu
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Xinxin Zhang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Shizhou Qi
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Ting Liu
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Kairu Song
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Da Wang
- School of Pharmacy, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| | - Huiyuan Gao
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
- Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 People's Republic of China
| |
Collapse
|
|
50
|
Ielciu I, Sevastre B, Olah NK, Turdean A, Chișe E, Marica R, Oniga I, Uifălean A, Sevastre-Berghian AC, Niculae M, Benedec D, Hanganu D. Evaluation of Hepatoprotective Activity and Oxidative Stress Reduction of Rosmarinus officinalis L. Shoots Tincture in Rats with Experimentally Induced Hepatotoxicity. Molecules 2021; 26:1737. [PMID: 33804618 PMCID: PMC8003693 DOI: 10.3390/molecules26061737] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/08/2021] [Accepted: 03/16/2021] [Indexed: 12/14/2022] Open
Abstract
Rosmarinus officinalis L. is a widely known species for its medicinal uses, that is also used as raw material for the food and cosmetic industry. The aim of the present study was to offer a novel perspective on the medicinal product originating from this species and to test its hepatoprotective activity. The tested sample consisted in a tincture obtained from the fresh young shoots. Compounds that are evaluated for this activity are polyphenols and terpenoids, that are identified and quantified by HPLC-UV-MS and GC-MS. Antioxidant activity was assessed in vitro, using the DPPH, FRAP and SO assays. Hepatoprotective activity was tested in rats with experimentally-induced hepatotoxicity. In the chemical composition of the tincture, phenolic diterpenes (carnosic acid, carnosol, rosmanol, rosmadial) and rosmarinic acid were found to be the majority compounds, alongside with 1,8-cineole, camphene, linalool, borneol and terpineol among monoterpenes. In vitro, the tested tincture proved significant antioxidant capacity. Results of the in vivo experiment showed that hepatoprotective activity is based on an antioxidant mechanism. In this way, the present study offers a novel perspective on the medicinal uses of the species, proving significant amounts of polyphenols and terpenes in the composition of the fresh young shoots tincture, that has proved hepatoprotective activity through an antioxidant mechanism.
Collapse
Affiliation(s)
- Irina Ielciu
- Department of Pharmaceutical Botany, Iuliu Haţieganu University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania;
| | - Bogdan Sevastre
- Department of Clinic and Paraclinic Sciences, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania;
| | - Neli-Kinga Olah
- PlantExtrakt, 407059 Cluj-Napoca, Romania; (N.-K.O.); (A.T.)
- Department of Pharmaceutical Industry, Faculty of Pharmacy, Vasile Goldiş Western University of Arad, 310414 Arad, Romania
| | - Andreea Turdean
- PlantExtrakt, 407059 Cluj-Napoca, Romania; (N.-K.O.); (A.T.)
| | - Elisabeta Chișe
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Vasile Goldiş Western University of Arad, 310414 Arad, Romania;
| | - Raluca Marica
- Department of Clinic and Paraclinic Sciences, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania;
| | - Ilioara Oniga
- Department of Pharmacognosy, Iuliu Haţieganu University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania; (I.O.); (D.H.)
| | - Alina Uifălean
- Department of Pharmaceutical Analysis, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Alexandra C. Sevastre-Berghian
- Department of Physiology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Mihaela Niculae
- Department of Clinical Sciences, Division and Infectious Diseases, University of Agricultural Sciences and Veterinary Medicine, 400374 Cluj-Napoca, Romania;
| | - Daniela Benedec
- Department of Pharmacognosy, Iuliu Haţieganu University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania; (I.O.); (D.H.)
| | - Daniela Hanganu
- Department of Pharmacognosy, Iuliu Haţieganu University of Medicine and Pharmacy, 400010 Cluj-Napoca, Romania; (I.O.); (D.H.)
| |
Collapse
|