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Huang H, Ru SJ, Chen JM, Liu W, Fang SH, Liu Q, Meng Q, Liu P, Zhou H. Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/PDCD4/JNK Pathway in Hepatic Stellate Cells. Drug Des Devel Ther 2025; 19:3735-3749. [PMID: 40356680 PMCID: PMC12067723 DOI: 10.2147/dddt.s500439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 04/05/2025] [Indexed: 05/15/2025] Open
Abstract
Purpose Hepatic fibrosis is a major cause of morbidity and mortality for which there is currently limited therapy. Amygdalin, a cyanogenic glucoside derived from Semen Persicae, exerts significant anti-fibrotic effects in the liver. However, the molecular mechanism by which amygdalin inhibits the progression of liver fibrosis remains unclear. This study aimed to elucidate the potential mechanism of action of amygdalin against liver fibrosis. Methods Quantitative proteomic profiling of the mouse liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis, and amygdalin-treated groups was performed to explore the key effector proteins of amygdalin. Histology and immunohistochemistry as well as serum biochemical analysis were performed to evaluate amygdalin efficacy in mice. The key gene programmed cell death protein 4 (PDCD4) was overexpressed or knocked down in human hepatic stellate cells (HSCs). The mRNA and protein levels of related molecules were detected by RT-qPCR and Western blotting, respectively. Results Amygdalin could effectively ameliorated CCl4-induced liver fibrosis in mice. Bioinformatics analysis revealed that PDCD4 was downregulated in CCl4-induced liver fibrosis, but amygdalin treatment reversed these changes. An in vitro study showed that PDCD4 inhibited the activation of human hepatic stellate cell line LX-2 cells by regulating the JNK/c-Jun pathway and amygdalin inhibited the activation of LX-2 cells in a PDCD4-dependent manner. We further found that amygdalin inhibited the phosphorylation of PDCD4 at Ser67 by inhibiting the mTOR/S6K1 pathway to enhance PDCD4 expression. Conclusion Our data demonstrated a potential pharmaceutical mechanism by which amygdalin alleviates liver fibrosis by inhibiting the mTOR/PDCD4/JNK pathway in HSCs, suggesting that PDCD4 is a potential target for the treatment of liver fibrosis.
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Affiliation(s)
- Hui Huang
- School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, People’s Republic of China
- Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Su-Jie Ru
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
| | - Jia-Mei Chen
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, People’s Republic of China
| | - Wei Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, People’s Republic of China
| | - Shan-Hua Fang
- Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Qian Liu
- Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Qian Meng
- Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
| | - Ping Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, People’s Republic of China
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China
| | - Hu Zhou
- School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, People’s Republic of China
- Department of Analytical Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
- University of Chinese Academy of Sciences, Beijing, People’s Republic of China
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Xu Y, Wang XS, Zhou XL, Lu WM, Tang XK, Jin Y, Ye JS. Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies. World J Gastroenterol 2024; 30:3766-3782. [PMID: 39221071 PMCID: PMC11362880 DOI: 10.3748/wjg.v30.i32.3766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/22/2024] [Accepted: 08/06/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.
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Affiliation(s)
- Yan Xu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xue-Song Wang
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xiao-Lei Zhou
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Wen-Ming Lu
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Xing-Kun Tang
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Department of Medical Genetics, School of Medicine, Tongji University, Shanghai 200092, China
| | - Yu Jin
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
| | - Jun-Song Ye
- Subcenter for Stem Cell Clinical Translation, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Ganzhou Key Laboratory of Stem Cell and Regenerative Medicine, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cere-brovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
- Jiangxi Provincal Key Laboratory of Tissue Engineering, Gannan Medical University, Ganzhou 341000, Jiangxi Province, China
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Ahmed EH, Abdeen MA, Soliman S. Impact of chlorogenic acid on submandibular salivary gland and liver of albino rats exposed to sodium nitrite. BMC Oral Health 2024; 24:911. [PMID: 39112979 PMCID: PMC11308576 DOI: 10.1186/s12903-024-04661-4] [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: 05/03/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
AIM The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. METHODS A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. RESULTS Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). CONCLUSIONS Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver.
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Affiliation(s)
- Elham H Ahmed
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt.
| | - Mohammed Abdelrahim Abdeen
- Department of Supplementary Medical Science (Human Anatomy), Faculty of Dentistry, Sinai University, North Sinai, Egypt
| | - Samar Soliman
- Department of Oral Pathology, Faculty of Dentistry, Mansoura University, Mansoura, Egypt
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Zhou X, Fu Y, Chen J, Liu P. Progress in clinical and basic research of fuzheng Huayu formula for the treatment of liver fibrosis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 327:118018. [PMID: 38453100 DOI: 10.1016/j.jep.2024.118018] [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: 07/07/2023] [Revised: 02/21/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine has great potential and advantages in the treatment of liver fibrosis, with Fuzheng Huayu formula (FZHY) serving as a prime example due to its remarkable efficacy in delaying and reversing liver fibrosis while simultaneously improving clinical symptoms for patients. AIM OF THE REVIEW In this paper, we present a comprehensive review of recent studies on the therapeutic potential of FZHY and its components/ingredients in the treatment of liver fibrosis and cirrhosis, with the aim of providing insights for future research endeavors. MATERIALS AND METHODS A comprehensive literature search was conducted on FZHY, TCM319, traditional Chinese medicine 319, liver fibrosis and cirrhosis using multiple internationally recognized databases including PubMed, Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails. Gov, CNKI, Wanfang, and VIP. RESULTS FZHY is widely used clinically for liver fibrosis and cirrhosis caused by various chronic liver diseases, with the effects of improving serum liver function, liver pathological histology, serological indices related to liver fibrosis, decreasing liver stiffness values and portal hypertension, as well as reducing the incidence of hepatocellular carcinoma and morbidity/mortality in patients with cirrhosis. Numerous in vivo and in vitro experiments have demonstrated that FZHY possesses anti-fibrotic effects by inhibiting hepatic stellate cell activation, reducing inflammation, protecting hepatocytes, inhibiting hepatic sinusoidal capillarization and angiogenesis, promoting extracellular matrix degradation, and facilitating liver regeneration. In recent years, there has been a growing focus on investigating the primary active components/ingredients of FZHY, and significant strides have been made in comprehending their synergistic mechanisms that enhance efficacy. CONCLUSION FZHY is a safe and effective drug for treating liver fibrosis. Future research on FZHY should focus on its active components/ingredients and their synergistic effects, as well as the development of modern cocktail drugs based on its components/ingredients. This will facilitate a more comprehensive understanding of the molecular mechanisms and targets of FZHY in treating liver fibrosis, thereby further guide clinical applications and drug development.
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Affiliation(s)
- Xiaoxi Zhou
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yadong Fu
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; State Key Laboratory of Cell Biology, Center for Excellence in Molecular and Cellular Sciences, Chinese Academy of Sciences, Shanghai, China
| | - Jiamei Chen
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Ping Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Zhang W, Sun J, Liu F, Li S, Wang X, Su L, Liu G. Alleviative Effect of Lactoferrin Interventions Against the Hepatotoxicity Induced by Titanium Dioxide Nanoparticles. Biol Trace Elem Res 2024; 202:624-642. [PMID: 37191759 DOI: 10.1007/s12011-023-03702-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 05/08/2023] [Indexed: 05/17/2023]
Abstract
The current study was designed to investigate the alleviative effect of lactoferrin interventions against the hepatotoxicity induced by titanium dioxide nanoparticles (TiO2-NPs). Thirty male Wistar rats were divided into six groups with 5 rats in each group. The first and second groups were intragastrically administered normal saline and TiO2-NPs (100 mg/kg body weight) as the negative control (NC) and TiO2-NP groups. The third, fourth, and fifth groups were intragastrically administered lactoferrin at concentrations of 100, 200, and 400 mg/kg body weight in addition to TiO2-NPs (100 mg/kg body weight). The sixth group was intragastrically administered Fuzheng Huayu (FZHY) capsules at a concentration of 4.6 g/kg body weight in addition to TiO2-NPs (100 mg/kg body weight) as the positive control group. After treatment for 4 weeks, the concentrations of lactoferrin were optimized based on the liver index and function results. Subsequently, the alleviative effects of lactoferrin interventions against TiO2-NP-induced hepatotoxicity in rat liver tissues, including the effects on histological damage, oxidative stress-related damage, inflammation, fibrosis, DNA damage, apoptosis, and gene expression, were investigated using histopathological, biochemical, and transcriptomic assays. The results showed that 200 mg/kg lactoferrin interventions for 4 weeks not only ameliorated the liver dysfunction and histopathological damage caused by TiO2-NP exposure but also inhibited the oxidative stress-related damage, inflammation, fibrosis, DNA damage, and apoptosis in the liver tissues of TiO2-NP-exposed rats. The transcriptomic results confirmed that the alleviative effect of lactoferrin interventions against the TiO2-NP exposure-induced hepatotoxicity was related to the activation of the PI3K/AKT signaling pathway.
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Affiliation(s)
- Wenqi Zhang
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Jiaxin Sun
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Fangyuan Liu
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Shubin Li
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Xianjue Wang
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Liya Su
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China
| | - Gang Liu
- Key Laboratory of Medical Cell Biology, Clinical Medicine Research Center, Affiliated Hospital of Inner Mongolia Medical University, No. 1 Tongdao North Street, Hohhot, 010050, Inner Mongolia, China.
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Li Y, Lu Y, Nian M, Sheng Q, Zhang C, Han C, Dou X, Ding Y. Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease. Chin J Nat Med 2023; 21:643-657. [PMID: 37777315 DOI: 10.1016/s1875-5364(23)60443-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Indexed: 10/02/2023]
Abstract
Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
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Affiliation(s)
- Yanwei Li
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Yunrui Lu
- Liaoning University of Traditional Chinese Medicine, Shenyang 110000, China
| | - Mozuo Nian
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Qiuju Sheng
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Chong Zhang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Chao Han
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Xiaoguang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110000, China.
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Yuan Y, Lv X, Wu Y, Weng Y, Dai F, Ding H, Chen R, Zheng B, Zhao W, Tong Q, Ding J, Lou D, Lai Y, Chu X, Zhao L, Lu S, Kong Q. Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach. PLoS Negl Trop Dis 2023; 17:e0011626. [PMID: 37773953 PMCID: PMC10566724 DOI: 10.1371/journal.pntd.0011626] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/11/2023] [Accepted: 08/29/2023] [Indexed: 10/01/2023] Open
Abstract
BACKGROUND Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. METHODS The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. RESULTS ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. CONCLUSION ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced liver fibrosis in response to ART through transcriptomics approach.
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Affiliation(s)
- Yajie Yuan
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
- Department of Pathogen Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China
| | - Xinyue Lv
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Yahan Wu
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Youhong Weng
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
| | - Fangwei Dai
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Haojie Ding
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Riping Chen
- School of Public Health, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Bin Zheng
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Wenxia Zhao
- School of Public Health, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Qunbo Tong
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Jianzu Ding
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Di Lou
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Yunru Lai
- Department of Laboratory Medicine, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, China
| | - Xiaofeng Chu
- Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Zhejiang Academy of Medical Sciences, Hangzhou, China
| | - Longyou Zhao
- Department of Laboratory Medicine, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, China
| | - Shaohong Lu
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
| | - Qingming Kong
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China
- School of Basic Medicine and Forensics, Key Laboratory of Bio-tech Vaccine of Zhejiang Province, Engineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, China
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Mik P, Barannikava K, Surkova P. Biased Quantification of Rat Liver Fibrosis-Meta-Analysis with Practical Recommendations and Clinical Implications. J Clin Med 2023; 12:5072. [PMID: 37568474 PMCID: PMC10420125 DOI: 10.3390/jcm12155072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/21/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
For liver fibrosis assessment, the liver biopsy is usually stained with Masson's trichrome (MT) or picrosirius red (PSR) to quantify liver connective tissue (LCT) for fibrosis scoring. However, several concerns of such semiquantitative assessments have been raised, and when searching for data on the amount of LCT in healthy rats, the results vastly differ. Regarding the ongoing reproducibility crisis in science, it is necessary to inspect the results and methods, and to design an unbiased and reproducible method of LCT assessment. We searched the Medline database using search terms related to liver fibrosis, LCT and collagen, rat strains, and staining methods. Our search identified 74 eligible rat groups in 57 studies. We found up to 170-fold differences in the amount of LCT among healthy Wistar and Sprague-Dawley rats, with significant differences even within individual studies. Biased sampling and quantification probably caused the observed differences. In addition, we also found incorrect handling of liver fibrosis scoring. Assessment of LCT using stereological sampling methods (such as systematic uniform sampling) would provide us with unbiased data. Such data could eventually be used not only for the objective assessment of liver fibrosis but also for validation of noninvasive methods of the assessment of early stages of liver fibrosis.
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Affiliation(s)
- Patrik Mik
- Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic
- Biomedical Center and Department of Histology, Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic
| | - Katsiaryna Barannikava
- Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic
| | - Polina Surkova
- Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, alej Svobody 76, 323 00 Pilsen, Czech Republic
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Wan G, Chen Z, Lei L, Geng X, Zhang Y, Yang C, Cao W, Pan Z. The total polyphenolic glycoside extract of Lamiophlomis rotata ameliorates hepatic fibrosis through apoptosis by TGF-β/Smad signaling pathway. Chin Med 2023; 18:20. [PMID: 36829153 PMCID: PMC9951520 DOI: 10.1186/s13020-023-00723-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 02/07/2023] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND Hepatic fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) which is mainly secreted by activated hepatic stellate cells (HSCs). Lamiophlomis rotata (L. rotata) was recorded to treat jaundice in the traditional Tibetan medical system with the potential of hepatoprotection. However, the bioactivities and the possible mechanism of L. rotata on hepatic fibrosis is still largely unknown. AIM OF THE STUDY To investigate the anti-hepatic fibrosis effects of bioactivities in L. rotata and the probable mechanism of action. MATERIALS AND METHODS Herein, total polyphenolic glycosides of L. rotata (TPLR) was purified with the selectivity adsorption resin and was analyzed by ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q/TOF/MSn). The anti-hepatic fibrosis effect of TPLR was evaluated by carbon tetrachloride (CCl4)-induced liver fibrosis, and was evaluated with the apoptosis of activated HSCs. RESULTS In total, sixteen compounds, including nine phenylpropanoids and six flavonoids, were identified in the UPLC-TOF-MSn profile of the extracts. TPLR significantly ameliorated hepatic fibrosis in CCl4-induced mice and inhibited HSCs proliferation, Moreover, TPLR notably increased the apoptosis of activated HSCs along with up-regulated caspase-3, -8, -9, and -10. Furthermore, TPLR inhibited TGF-β/Smad pathway ameliorating hepatic fibrosis though downregulation the expression of Smad2/3, Smad4, and upregulation the expression of Smad7 in vivo and in vitro. Simultaneously, the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and Collagen I (Col1α1) were decreased in tissues and in cells with TPLR administration. CONCLUSION These results initially demonstrated that TPLR has the potential to ameliorate hepatic fibrosis through an apoptosis mechanism via TGF-β/Smad signaling pathway.
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Affiliation(s)
- Guoguo Wan
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Zhiwei Chen
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Lei Lei
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Xiaoyu Geng
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Yi Zhang
- grid.411304.30000 0001 0376 205XCentre for Academic Inheritance and Innovation of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130 China
| | - Congwen Yang
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Wenfu Cao
- grid.203458.80000 0000 8653 0555Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016 People’s Republic of China
| | - Zheng Pan
- Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
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Ye Z, Huang Q, She Y, Hu Y, Wu M, Qin K, Li L, Zhang C, Zuo X, Wei A, Mao D, Ye Q. A meritorious integrated medical regimen for hepatic fibrosis and its complications via the systematic review and meta-analysis for Dahuang Zhechong pill-based therapy. Front Med (Lausanne) 2022; 9:920062. [PMID: 36314011 PMCID: PMC9616118 DOI: 10.3389/fmed.2022.920062] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Background Hepatic fibrosis is a health challenge due to the absence of satisfactory therapy, especially at the cirrhosis stage. Dahuang Zhechong pill (DHZCP)-based therapy is reportedly a successful treatment for hepatic fibrosis and is even beneficial for the treatment of cirrhosis. Hence, a systematic review and clinical evidence assessment of DHZCP-based therapy should be performed, and clinical recommendations based on its efficacy for the treatment of hepatic fibrosis should be generated. With respect to potential indicators, the comparative value of the hepatic function, spleen thickness, and portal vein internal diameter should be evaluated. Materials and methods PubMed, the Excerpta Medica Database, the Cochrane Library, the Web of Science, the WanFang Database, the Chinese Scientific Journal Database, and the Chinese National Knowledge Infrastructure database were searched to identify clinical trials. Three subgroup analyses were performed based on the stage of disease, medication use, and the course of treatment. Statistical analyses were performed using Review Manager 5.4. Results A total of 18 studies including 1,494 patients were evaluated. The DHZCP-based therapy was effective in reducing the plasma levels of hyaluronic acid, and laminin, procollagen III, and IV collagen were also reduced irrespective of the hepatitis stage or the presence of hepatic cirrhosis. Abnormalities in alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin were reversed. A 6-month course of treatment was the most beneficial DHZCP-based therapy regimen. Alanine aminotransferase improvement was more obvious in patients with cirrhosis, and alanine aminotransferase was reduced significantly in patients with hepatic cirrhosis. With respect to pharmacological mechanisms, DHZCP-based therapy could inhibit hepatic stellate cell growth and activation, reduce inflammation, and prevent extracellular matrix formation. Hepatic portal hypertension and splenomegaly were ameliorated significantly in the DHZCP-based therapy group. Conclusion Dahuang Zhechong pill-based therapy has demonstrated efficacy as a treatment for hepatic fibrosis and cirrhosis. A 6-month course of treatment is the recommended option for DHZCP-based therapy in clinical practice. The combination of DHZCP-based therapy and entecavir is a favorable treatment for hepatic cirrhosis.
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Affiliation(s)
- Zhen Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qinfeng Huang
- Department of Oncology, The First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, China
| | - Yingqi She
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Hu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mingquan Wu
- Department of Pharmacy, Sichuan Orthopedic Hospital, Chengdu, Sichuan, China
| | - Kaihua Qin
- Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Linzhen Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuantao Zhang
- Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiaohong Zuo
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ailing Wei
- Department of Liver Disease, The First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, China
| | - Dewen Mao
- Department of Liver Disease, The First Affiliated Hospital, Guangxi University of Chinese Medicine, Nanning, China
| | - Qiaobo Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China,*Correspondence: Qiaobo Ye,
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Tan W, Wang Y, Dai H, Deng J, Wu Z, Lin L, Yang J. Potential Therapeutic Strategies for Renal Fibrosis: Cordyceps and Related Products. Front Pharmacol 2022; 13:932172. [PMID: 35873549 PMCID: PMC9304961 DOI: 10.3389/fphar.2022.932172] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/01/2022] [Indexed: 12/02/2022] Open
Abstract
At present, there is no effective drug for the treatment of renal fibrosis; in particular, a safe and effective treatment for renal fibrosis should be established. Cordyceps has several medical effects, including immunoregulatory, antitumor, anti-inflammatory, and antioxidant effects, and may prevent kidney, liver, and heart diseases. Cordyceps has also been reported to be effective in the treatment of renal fibrosis. In this paper, we review the potential mechanisms of Cordyceps against renal fibrosis, focusing on the effects of Cordyceps on inflammation, oxidative stress, apoptosis, regulation of autophagy, reduction of extracellular matrix deposition, and fibroblast activation. We also discuss relevant published clinical trials and meta-analyses. Available clinical studies support the possibility that Cordyceps and related products provide benefits to patients with chronic kidney diseases as adjuvants to conventional drugs. However, the existing clinical studies are limited by low quality and significant heterogeneity. The use of Cordyceps and related products may be a potential strategy for the treatment of renal fibrosis. Randomized controlled trial studies with good methodological quality, favorable experimental design, and large sample size are needed to evaluate the efficacy and safety of Cordyceps.
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Affiliation(s)
- Wei Tan
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yunyan Wang
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongmei Dai
- Nephrology, YunYang County People’s Hospital, Chongqing, China
| | - Junhui Deng
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhifen Wu
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lirong Lin
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jurong Yang
- Nephrology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Jurong Yang,
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Pathogenesis of Liver Fibrosis and Its TCM Therapeutic Perspectives. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:5325431. [PMID: 35529927 PMCID: PMC9071861 DOI: 10.1155/2022/5325431] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 03/15/2022] [Indexed: 12/16/2022]
Abstract
Liver fibrosis is a pathological process of abnormal tissue proliferation in the liver caused by various pathogenic factors, which will further develop into cirrhosis or even hepatocellular carcinoma if liver injury is not intervened in time. As a diffuse progressive liver disease, its clinical manifestations are mostly excessive deposition of collagen-rich extracellular matrix resulting in scar formation due to liver injury. Hepatic fibrosis can be caused by hepatitis B and C, fatty liver, alcohol, and rare diseases such as hemochromatosis. As the metabolic center of the body, the liver regulates various vital activities. During the development of fibrosis, it is influenced by many other factors in addition to the central event of hepatic stellate cell activation. Currently, with the increasing understanding of TCM, the advantages of TCM with multiple components, pathways, and targets have been demonstrated. In this review, we will describe the factors influencing liver fibrosis, focusing on the effects of cells, intestinal flora, iron death, signaling pathways, autophagy and angiogenesis on liver fibrosis, and the therapeutic effects of herbal medicine on liver fibrosis.
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Zhang C, Zhang D, Wang Y, Zhang L, Qi S, Fang Q, Xu Y, Chen J, Cheng X, Liu P, Wang C, Liu W. Pharmacokinetics and anti-liver fibrosis characteristics of amygdalin: Key role of the deglycosylated metabolite prunasin. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 99:154018. [PMID: 35247668 DOI: 10.1016/j.phymed.2022.154018] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/24/2022] [Accepted: 02/25/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Amygdalin (Amy) is a cyanoside and is one of the chief active ingredients in Persicae Semen, Armeniacae Semen Amarum, and Pruni Semen. Amy has extensive and remarkable pharmacological activities, including against anti-hepatic fibrosis. However, the pharmacokinetic and anti-liver fibrosis effects of Amy and its enzyme metabolite prunasin (Pru) in vivo have not been studied and compared, and studies on Pru are limited. PURPOSE To investigate the pharmacokinetic characteristics and anti-liver fibrosis effect of Amy and its metabolite Pru in vivo and in vitro, and elucidate whether the metabolism of Amy in vivo for Pru is activated. METHODS Pru was prepared from Amy via the enzymatic hydrolysis of β-glucosidase, and isolated by silica gel column chromatography. An efficient and sensitive ultrahigh-performance liquid chromatography-Q exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry was developed and validated to determine simultaneously Amy and Pru in rat plasma after dosing intravenously and orally for pharmacokinetic studies. The affinities of Amy and Pru for β-glucosidase were compared by enzyme kinetic experiments to explain the possible reasons for the differences in pharmacokinetic behavior. In vitro, the inhibitory effects of Amy and Pru on hepatic stellate cell activation and macrophage inflammation on JS1 and RAW 264.7 cells were determined. In vivo, the ameliorative effects of Amy and Pru on liver fibrosis effects were comprehensively evaluated by CCl4-induced liver fibrosis model in mice. RESULTS The standard curves of Amy and Pru in rat plasma showed good linearity within the concentration range of 1.31-5000.00 ng/ml, with acceptable selectivity, carry-over, detection limit and quantification limits, intra- and inter-day precision, accuracy, matrix effect, and stability. The Cmax and AUC(0-∞) of Pru (Cmax = 1835.12 ± 268.09 ng/ml, AUC(0-∞) = 103,913.17 ± 14,202.48 ng•min/ml) were nearly 79.51- and 66.22-fold higher than those of Amy (Cmax = 23.08 ± 5.08 ng/ml, AUC(0-∞) = 1569.22 ± 650.62 ng•min/ml) after the oral administration of Amy. The oral bioavailability of Pru (64.91%) was higher than that of Amy (0.19%). The results of enzyme hydrolysis kinetics assay showed that the Vmax and Km of Pru were lower than those of Amy in commercial β-glucosidase and intestinal bacteria. In vitro cellular assays showed that Amy and Pru were comparable in inhibiting the NO production in the RAW264.7 cell supernatant and the mRNA expression of α-SMA and Col1A1 in JS1 cells. Amy and Pru were also showed comparable activity in ameliorating CCl4-induced liver fibrosis in mice. CONCLUSION The pharmacokinetic characteristics of Amy and Pru in rat plasma were significantly different. After the separate gavage of Amy and Pru, Amy was absorbed predominantly as it's metabolite Pru, whereas Pru was absorbed predominantly as a prototype. The anti-liver fibrosis effects of Amy and its deglycosylated metabolite Pru were comparable in vivo and in vitro. The deglycosylated activated metabolite Pru of Amy plays an important role in anti-liver fibrosis. These findings will facilitate the further exploitation of Amy and Pru.
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Affiliation(s)
- Congcong Zhang
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China
| | - Dingqi Zhang
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China
| | - Yongli Wang
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China
| | - Linzhang Zhang
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China
| | - Shenglan Qi
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China
| | - Qinqin Fang
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China; Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China
| | - Ying Xu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China
| | - Jiamei Chen
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China
| | - Xuemei Cheng
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China
| | - Ping Liu
- Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
| | - Changhong Wang
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China.
| | - Wei Liu
- Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rood, Shanghai 201203, China; Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
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Ma Z, Sheng L, Li J, Qian J, Wu G, Wang Z, Zhang Y. Resveratrol Alleviates Hepatic Fibrosis in Associated with Decreased Endoplasmic Reticulum Stress-Mediated Apoptosis and Inflammation. Inflammation 2022; 45:812-823. [PMID: 35080697 PMCID: PMC8956545 DOI: 10.1007/s10753-021-01586-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 10/14/2021] [Accepted: 10/18/2021] [Indexed: 11/24/2022]
Abstract
Hepatic fibrosis (HF) is the typical response to chronic liver disease and is characterized by deposition of abundant extracellular matrix. The aim of the present study was to investigate the protective effect of resveratrol (RSV) in a CCl4-induced rat model of HF. We demonstrate that the administration of RSV effectively improves liver function and ameliorates liver fibrosis by reducing collagen deposition and reversing the expression of COL1A1 and PPAR-γ. Treatment efficacy of RSV could be attributed to reversed epithelial-mesenchymal transition progress with upregulated expression of E-cadherin and downregulated N-cadherin, vimentin, and α-SMA. Moreover, RSV significantly decreased the levels of endoplasmic reticulum stress (ERS)-related proteins CHOP; Bip; cleaved caspase-3, caspase-7, and caspase-12; Bax; and Bak while promotes the expression of anti-apoptosis protein Bcl2. The important role of ERS in HF was confirmed by using 4-PBA, an ERS inhibitor, which markedly ameliorated CCl4-induced HF. Further, mechanistic studies demonstrated that RSV significantly decreased CCl4-induced transforming growth factor-β synthesis and inflammatory factor (tumor necrosis factor-α and interleukin-6) expression and reduced the inflammation of hepatic stellate cells by inhibiting the NF-κB pathway in vivo and in vitro. In conclusion, the results suggested that RSV ameliorated HF in associated with decreased ERS-induced apoptosis and inflammation in rats.
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Affiliation(s)
- Zhenyu Ma
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Lulu Sheng
- Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Juan Li
- Department of Nursing Center, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Jianmin Qian
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Gang Wu
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Zhengxin Wang
- Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
| | - Yi Zhang
- Biomedical Research Center, Institute for Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. .,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
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Shen BD, Deng L, Liu Y, Li RS, Shen CY, Liu X, Li YC, Yuan HL. Effects of novel Fufang Biejia Ruangan Tablets with sheep placenta as substitute for hominis placenta on CCl4-induced liver fibrosis. CHINESE HERBAL MEDICINES 2021; 14:104-110. [PMID: 36120135 PMCID: PMC9476806 DOI: 10.1016/j.chmed.2021.09.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/25/2021] [Accepted: 09/08/2021] [Indexed: 12/03/2022] Open
Abstract
Objective Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However, Hominis Placenta (HP), as an important adjuvant of FBRT, has been restricted for medicinal using due to the limited availability, ethical controversy and safety issues. The present study aimed to investigate the therapeutic effects of novel FBRT (N-FBRT) with sheep placenta (SP) as substitute for HP on liver fibrosis and explore its possible mechanisms. Different dosages of SP in N-FBRT were also evaluated. Methods Rats were subcutaneously injected with CCl4 to induce liver fibrosis and then treated with N-FBRT and FBRT. The anti-hepatic fibrosis effect was determined based on biomarkers analysis of liver function and hepatic fibrosis, and the liver pathology was visualized by H&E staining and Masson staining. The oxidative stress and inflammatory cytokines were also detected. Immunohistochemical staining of α-SMA, real time PCR and Western blotting were performed to evaluate hepatic stellate cells (HSCs) activation and TGF-β1/Smad signaling pathway. Results N-FBRT and FBRT could ameliorate CCl4-induced liver fibrosis and improve liver function, as evidenced by lowering serum biomarkers levels of liver function and hepatic fibrosis, and decreasing hepatic Hyp content and collagen deposition, and improving the hepatic morphology and architecture changes. Moreover, the anti-liver fibrosis effect was better when the dosage of SP used in N-FBRT was 1/2 of HP in FBRT. Administration of N-FBRT markedly alleviated oxidative stress and inflammatory cytokines, and inhibited α-SMA expression. Furthermore, the mRNA expression of Col I, Col III, α-SMA and TGF-β1, and proteins expression of α-SMA, TGF-β1, Smad2/3 and p-Smad2/3 were significantly down-regulated by N-FBRT treatment. Conclusion SP can be used as substitute for HP to prepare N-FBRT for the treatment of liver fibrosis and the anti-liver fibrosis effect of N-FBRT is achieved by eliminating oxidative stress and inflammation, and inhibiting HSCs activation and ECM production by blocking TGF-β1/Smad signaling pathway.
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Liu Q, Chen X, Kan M, Yang J, Gong Q, Jin R, Dai Y, Jin J, Zang H. Gypenoside XLIX loaded nanoparticles targeting therapy for renal fibrosis and its mechanism. Eur J Pharmacol 2021; 910:174501. [PMID: 34529980 DOI: 10.1016/j.ejphar.2021.174501] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 09/07/2021] [Accepted: 09/09/2021] [Indexed: 01/18/2023]
Abstract
Renal fibrosis is the main pathological feature of the occurrence and development of chronic nephropathy. At present, there is no effective treatment, except for renal transplantation and dialysis. Previous studies have shown that nano-preparations can be used as a therapeutic tool to target organs. In this study, we studied the therapeutic effect and mechanism of Chinese medicine monomer Gypenoside (Gyp) XLIX on renal fibrosis and explored the targeting and therapeutic effects of polylactic acid-co-glycoside (PLGA)-Gyp XLIX nanoparticles in unilateral ureteral occlusion (UUO) kidney. Gyp XLIX and PLGA-Gyp XLIX nanoparticles were used to treat UUO mice and Human renal tubular epithelial (HK2) cells stimulated by transforming growth factor-β (TGF-β). Histopathological and molecular biological techniques were used to detect the expression of type I collagen and alpha-smooth muscle actin (α-SMA). To investigate the in vivo targeting of PLGA nanoparticles, they were loaded with 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide and injected into UUO mice. We evaluated the effect of Gyp XLIX nanoparticles on TGF-β/Smad3 pathway, a central driver for renal fibrosis in Smad-deficient HK2 cells. Fluorescence imaging showed that the PLGA nanoparticles around 120 nm could be targeted to the UUO kidney. Compared with Gyp XLIX, PLGA-Gyp XLIX nanoparticles could effectively inhibit renal fibrosis and reduce collagen deposition and reduce renal tubular necrosis. Gyp XLIX decreased the phosphorylation of Smad3, but could not further reduce the levels of type I collagen and α-SMA in Smad-deficient cells. This study opens a promising way for targeted drug treatment of renal fibrosis.
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Affiliation(s)
- Qixia Liu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China
| | - Xiaohui Chen
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China
| | - Min Kan
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China
| | - Jing Yang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China
| | - Qian Gong
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, China
| | - Rui Jin
- People's Hospital of Jieshou City, Jieshou, 236500, Anhui, China
| | - Yulong Dai
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China
| | - Juan Jin
- Department of Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China.
| | - Hongmei Zang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, 230032, China.
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Wang R, Zhang D, Tang D, Sun K, Peng J, Zhu W, Yin S, Wu Y. Amygdalin inhibits TGFβ1-induced activation of hepatic stellate cells (HSCs) in vitro and CCl 4-induced hepatic fibrosis in rats in vivo. Int Immunopharmacol 2021; 90:107151. [PMID: 33296784 DOI: 10.1016/j.intimp.2020.107151] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 09/22/2020] [Accepted: 10/20/2020] [Indexed: 02/07/2023]
Abstract
The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate pain; however, its role and mechanism in HSC activation and hepatic fibrosis remain unclear. In the present study, transforming growth factor-beta 1 (TGF-β1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (α-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-β1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-β1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), and chemokine (C-C motif) ligand 2 (CCL2), as well as the phosphorylation of Smad2, Smad3, and p65. In the CCl4-stimulated liver fibrosis rat model, amygdalin treatment improved liver fibrosis and liver damage by reducing focal necrosis, collagen fiber accumulation, and the protein levels of α-SMA, desmin, collagen I, and TIMP-1 in hepatic tissue samples and reducing serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In conclusion, we demonstrated the suppressive effects of amygdalin in TGF-β1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl4-stimulated hepatic fibrosis in rats in vivo.
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Affiliation(s)
- Ruoyu Wang
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Dong Zhang
- Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine in Zhuhai, Zhuhai, Guangdong 519015, China
| | - Dan Tang
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Kewei Sun
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Jianping Peng
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Wenfang Zhu
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Sihan Yin
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
| | - Yunan Wu
- Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China.
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Li K, Ma C, Li H, Dev S, He J, Qu X. Medicinal Value and Potential Therapeutic Mechanisms of Gynostemma pentaphyllum (Thunb.) Makino and Its Derivatives: An Overview. Curr Top Med Chem 2020; 19:2855-2867. [PMID: 31724506 DOI: 10.2174/1568026619666191114104718] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 08/25/2019] [Accepted: 09/02/2019] [Indexed: 12/12/2022]
Abstract
:
Gynostemma pentaphyllum (Thunb.) Makino (GpM) and its derivatives, especially gypenosides
(Gyps), are widely used as safe and convenient natural herbal drugs for the treatment of many
diseases for a long time, and Gyps have different oral bioavailability (OB) values and low ability to
cross the blood-brain barrier (BBB). The effects of GpM and isolates on fibrosis, inflammation, oxidation,
proliferation and migration are proved. GpM shows bidirectional regulation effect on proliferation,
oxidation and apoptosis in tumor and non-tumor cells. GpM and its extractions can resist proliferation,
activate oxidation and apoptosis in tumor cells and have opposite effects on non-tumor cells. We succinctly
present some current views of medicinal value and potential therapeutic mechanisms of GpM
and its derivatives.
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Affiliation(s)
- Kaijun Li
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Chao Ma
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Haoyu Li
- Graduate School, Guangxi University of Chinese Medicine, Guangxi, China
| | - Sooranna Dev
- Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, 369, Fulham Road, London SW10 9NH, United Kingdom
| | - JianFeng He
- Department of Ophthalmology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Xiaosheng Qu
- National Engineering laboratory of Southwest Endangered Medicinal Resources Development, Guangxi Botanical Garden of Medicinal Plants, Guangxi, China
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Ma L, Wang X, Li W, Qu F, Liu Y, Lu J, Su G, Zhao Y. Conjugation of Ginsenoside with Dietary Amino Acids: A Promising Strategy To Suppress Cell Proliferation and Induce Apoptosis in Activated Hepatic Stellate Cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:10245-10255. [PMID: 31389238 DOI: 10.1021/acs.jafc.9b03305] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Ginseng has been widely used as a functional food in the world because of its well-defined health benefits. Previous studies have confirmed that AD-1, a new ginsenoside derived from ginseng, can ameliorate thioacetamide-induced liver injury and fibrosis in mice. Simultaneously, amino acid supplementation is getting more attention as an important adjuvant therapy in the improvement of hepatopathy. The aim of this study was to conjugate AD-1 with several selected amino acids and investigate the cytotoxicity of the obtained conjugates in activated t-HSC/Cl-6 cells and normal human liver cells (LO2). Structure-activity relationships of conjugates and underlying mechanisms of the effect are also explored. The results indicated that conjugate 7c remarkably inhibited cell proliferation in activated t-HSC/Cl-6 cells (IC50 = 3.8 ± 0.4 μM) and appeared to be nontoxic to LO2. Besides, conjugate 7c had a relatively good plasma stability. Further study demonstrated that inducing S-phase arrest and activation of mitochondrial-mediated apoptosis were included in the mechanisms underlying the efficiency of conjugate 7c. These findings provided further insight into designing functional foods (ginsenoside and amino acid) for the application in prevention or improvement of liver fibrosis.
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Liu L, Zhang H, Wang Z, Song D. Peptide-functionalized upconversion nanoparticles-based FRET sensing platform for Caspase-9 activity detection in vitro and in vivo. Biosens Bioelectron 2019; 141:111403. [DOI: 10.1016/j.bios.2019.111403] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/22/2019] [Accepted: 06/01/2019] [Indexed: 12/17/2022]
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Hu XQ, Song YN, Wu R, Cai FF, Zhang Y, Peng JH, Hu YY, Su SB. Metabolic mechanisms of Fuzheng-Huayu formula against liver fibrosis in rats. JOURNAL OF ETHNOPHARMACOLOGY 2019; 238:111888. [PMID: 31004725 DOI: 10.1016/j.jep.2019.111888] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 03/31/2019] [Accepted: 04/12/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Fuzheng-Huayu formula (FZHY) is traditionally used to treat liver fibrosis in clinic. The study was conducted to investigate the metabolic mechanisms of FZHY against liver fibrosis in rats. MATERIALS AND METHODS Rats with CCl4 -induced liver fibrosis were treated with FZHY and its components, including amygdalin, cordyceps polysaccharide and gypenoside, respecitively. Liver fibrosis and function were assesed by histopathological examination, Western blot and serum biochemical detection. Metabolic profiling of liver tissue, serum and urine in each group were detected by gas chromatography-mass spectrometry (GC-MS) and transcriptomic changes were tested by gene chip. RT-qPCR was used to validate levels of different expressed genes (DEGs) with statistical significance. Metabolic network together with DEGs was constructed based on KEGG database. RESULTS FZHY effectively improved liver fibrosis better than the mixture or single use of gypenoside, cordyceps sinensis mycelia and amygdalin. FZHY treatment widely modulated the metabolic profiles perturbed by liver fibrosis, involving several important metabolic pathways, including glycolysis/gluconeogenesis, glucose-alanine cycle, citrate cycle, galactose metabolism, tryptophan metabolism, urea cycle, etc. It also increased alanine and decreased glucose levels in liver tissue and decreased both of them in serum and urine, which were dysregulated by CCl4 treatment. Additionally, FZHY also upregulated expression of metabolic enzymes including Hk2, Adh1 and Gpt increased, and downregulated Gs and Acss2. CONCLUSION FZHY improved liver fibrosis in rats via altering the metabolic pathways and regulating gene expression of involved metabolic enzymes.
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Affiliation(s)
- Xue-Qing Hu
- Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ya-Nan Song
- Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, china
| | - Rong Wu
- Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Fei-Fei Cai
- Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yongyu Zhang
- Research Center for Traditional Chinese Medicine and System Biology, Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jing-Hua Peng
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yi-Yang Hu
- Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Shi-Bing Su
- Research Center for Complex System of Traditional Chinese Medicine, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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The components data of fuzheng huayu extracts, cordyceps sinensis mycelia polysaccharide, gypenosides and amygdalin. Data Brief 2019; 25:104087. [PMID: 31294053 PMCID: PMC6595274 DOI: 10.1016/j.dib.2019.104087] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 05/07/2019] [Accepted: 05/27/2019] [Indexed: 11/23/2022] Open
Abstract
Fuzheng Huayu (FZHY) capsule is a traditional Chinese medicine composed of six Chinese medicinal herbs Tian et al. [1] and approved by China food and drug administration for liver fibrosis treatment [2], [3] Liu et al., 2009 and Liu et al., 2005. CGA formula consisting of Cordyeps sinensis polysaccharide (CS-PS), gypenosides (G), and amygdalin (A), are derived from FZHY formula. It is necessary to identify the chemical profile of FZHY and CGA formula to describe the mechanisms and the corresponding components of anti-fibrosis. It is showed that FZHY contains adenosine (5.21 mg/g), amygdalin (5.31 mg/g), salvianolic acid b (18.22 mg/g) and deoxyschizandrin (2.62 mg/g), respectively. CS-PS contained 60.5 ± 2.2% total carbohydrate, including 14.17% arabinose, 25.35% glucose and 60.48% galactose. Gypenosides contain 10.34% gypenosides XLIX and 16.58% gypenosides A. These data provide the primary chemical profile of FZHY and CGA formula and an example for components analysis of traditional Chinese medicine.
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