bicyclol and Non-alcoholic-Fatty-Liver-Disease

Non-alcoholic fatty liver disease (NAFLD) is a global epidemic without effective therapeutic agents in the clinic. This meta-analysis aimed to assess the efficacy of the marketed hepatoprotectant bicyclol at improving blood biomarkers in patients with NAFLD.. Electronic databases were searched for randomised controlled trials (RCTs) published up to August 2020 using bicyclol to treat NAFLD. The risk of bias, quality of evidence and publication bias were evaluated. Blood biomarkers, including alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), triglyceride (TG) and total cholesterol (TC), were analysed using Review Manager V.5.3 software. Outcomes with significant heterogeneity (I. Twelve RCTs involving 1008 patients were finally included. No serious adverse events were reported in the bicyclol-treated groups. The total effective rate of bicyclol intervention for NAFLD was significantly higher than that of the control group. The decreases in the levels of AST (mean difference (MD) = -15.20; 95% CI -20.51 to -9.90; I. The study presents the evidence of bicyclol monotherapy and/or combination therapy for improving liver function and blood lipid biomarkers in patients with NAFLD. This preliminary study predicts that bicyclol might be an alternative drug for NAFLD therapy in the future.

Topics: Alanine Transaminase; Biomarkers; Biphenyl Compounds; Humans; Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is associated with a high morbidity in patients with impaired fasting glucose (IFG). Bicyclol is a synthetic compound known to protect the liver against oxidation and lipid injuries.. The objective of this study was to evaluate the efficacy and safety of metformin and bicyclol in the treatment of NAFLD patients with IFG.. After lifestyle changes and metformin treatment (500 mg orally three times daily), the 248 patients enrolled with NAFLD and IFG were equally randomized to two 24-week treatment groups: bicyclol 25 mg three times daily or vitamin E (α-tocopherol) 100 mg three times daily (control). Anthropometric measurements, serum biochemistry, liver/spleen computed tomography ratio, and changes in liver histological parameters were compared before and after treatments.. A total of 223 patients completed the treatment, and there were significant improvements in body mass index, waist-to-hip ratio, and biochemical parameters in both groups (P < 0.01). Compared with the control group, the improvement in serum alanine aminotransferase levels in the bicyclol group was statistically significant (P < 0.01). Liver histological assessments revealed that steatosis, inflammation, hepatocellular ballooning, and NAFLD activity scores (NAS) were all decreased in both groups after treatment (P < 0.01). However, decreases in inflammation and NAS in the bicyclol group were statistically significant compared with the vitamin E group (P < 0.01). Adverse events in the bicyclol and control groups occurred in 1.79 and 1.80 %, respectively.. Metformin combined with bicyclol is effective and safe in the treatment of patients with NAFLD and IFG. However, further studies with a larger sample size are needed to confirm the efficacy and safety of the combination.

Topics: Alanine Transaminase; Biphenyl Compounds; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Liver; Male; Metformin; Non-alcoholic Fatty Liver Disease; Vitamin E

Topics: Adult; Biphenyl Compounds; Fatty Liver; Female; Humans; Hypolipidemic Agents; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phosphatidylcholines; Young Adult

To compare the effect of berberine and bicyclol on patients with nonalcoholic fatty liver disease (NAFLD).. Chinese nonalcoholic and non-viral hepatitis patients with a hepatic lipid content > 13% and nonalcoholic fatty liver disease activity score (NAS) ≥ 2 were treated with 500 mg berberine thrice daily, together with dietary modification (low-fat diet) and Tai Chi exercise for 4 months (BT cohort; n = 112), or 25 mg bicyclol thrice daily plus dietary modification and Tai Chi exercise for 4 months (CT cohort, n = 145), or dietary modification and Tai Chi exercise for 4 months (DT cohort, n = 128).. Patients in the BT and the CT cohorts had improved anthropometric measurements (weight, height, body mass index, and waist-to-hip ratio), biochemical parameters (blood sugar, lipid profile, and liver functions tests), liver/spleen computed tomography findings, and liver biopsy results after 4 months of intervention (. Berberine or bicyclol plus dietary modification and Tai Chi exercise could control NAFLD without serious adverse effects. Dietary modification and Tai Chi exercise alone for 4 months are insufficient for the management of NAFLD. It is possible to reduce body weight by administering berberine or bicyclol.

Topics: Berberine; Biphenyl Compounds; China; Humans; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Retrospective Studies

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome in the liver, and non-alcoholic steatohepatitis (NASH) represents its advanced stage. Bicyclol has protective activity against NAFLD in mice; however, the effect of bicyclol on high-fat diet (HFD)-induced NASH and its underlying molecular mechanism remains unknown particularly anti-endoplasmic reticulum (ER) stress and autophagic machinery potentials. Therefore, the present study was performed to investigate the protective effect and underlying mechanisms of bicyclol action on NAFLD/NASH.. Mice were fed an HFD to induce NAFLD/NASH, and bicyclol was administered as a treatment. Biochemistry and histopathological assays were performed to evaluate the effects of bicyclol on NAFLD/NASH. Moreover, the levels of hepatic ER stress- and autophagy-related markers were determined by western blotting.. The present results revealed that bicyclol exerted significant protective effects against HFD-induced NAFLD/NASH. This activity was evidenced by the decrease in elevated serum transaminase and hepatic triglyceride levels, and the attenuation of negative histopathological changes. Bicyclol considerably alleviated hepatic inflammation and apoptosis. The protein expression of ER stress-related markers, including C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), was downregulated by the bicyclol treatment in HFD-induced mice. However, the protein expression of autophagy-related markers (LC3 and Beclin 1) was upregulated by the treatment with bicyclol.. Bicyclol protected HFD-induced NASH, and partly due to its ability of reducing ER stress and promoting autophagy.

Topics: Animals; Autophagy; Biphenyl Compounds; Diet, High-Fat; Endoplasmic Reticulum Stress; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease

Bicyclol has been approved as an anti-inflammatory, hepatoprotective drug in China to treat various forms of hepatitis. However, the role of bicyclol in non-alcoholic fatty liver disease (NAFLD) is unknown. In this study, NAFLD model was established by feeding mice with high fat diet (HFD) for 16 weeks, and bicyclol (25 and 50 mg/kg) were orally administered for the last 4 weeks. Although bicyclol treatment did not change the body weight of mice, bicyclol administration significantly improved HFD-induced dyslipidemia, NAFLD activity score, hepatic apoptosis, systemic and hepatic inflammation, and liver fibrosis in the mice. Moreover, bicyclol treatment significantly inhibited HFD-induced activation of MAPKs and NF-κB signaling pathways that may mediate the inflammatory responses. Further in vitro studies showed that bicyclol pretreatment markedly ameliorated PA-induced inflammatory responses in human hepatocyte HL-7702 cells and mouse peritoneal macrophages through inhibiting MAPKs and NF-κB signaling pathways. These data indicated that bicyclol may have the potency to treat NAFLD by reducing inflammation.

Topics: Animals; Apoptosis; Biphenyl Compounds; Cells, Cultured; Diet, High-Fat; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Non-alcoholic Fatty Liver Disease; Protein Kinase Inhibitors

Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Tetracycline can cause hepatic steatosis, and ER stress may be involved in tetracycline-induced fatty liver. Our previous study showed that bicyclol has been proven to protect against tetracycline-induced fatty liver in mice, and ER stress may also be involved in bicyclol's hepatoprotective effect. Therefore, this study was performed to investigate the underlying mechanisms associated with ER stress and apoptosis, by which bicyclol attenuated tetracycline-induced fatty liver in mice. Bicyclol (300 mg/kg) was given to mice by gavage 3 times. Tetracycline (200 mg/kg, intraperitoneally) was injected at 1 h after the last dose of bicyclol. At 6 h and 24 h after single dose of tetracycline injection, serum ALT, AST, TG, CHO and hepatic histopathological examinations were performed to evaluate liver injuries. Hepatic steatosis was assessed by the accumulation of hepatic TG and CHO. Moreover, hepatic apoptosis and ER stress related markers were determined by TUNEL, real-time PCR, and western blot. As a result, bicyclol significantly protected against tetracycline-induced fatty liver as evidenced by the decrease of elevated serum transaminases and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated hepatic apoptosis and the gene expression of caspase-3, and increased the gene expression of XIAP. The gene expressions of ER stress-related markers, including CHOP, GRP78, IRE-1α, and ATF6, which were downregulated by bicyclol pretreatment in tetracycline-injected mice. These results suggested that bicyclol protected tetracycline-induced fatty liver partly due to its ability of anti-apoptosis associated with ER stress.

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Biphenyl Compounds; Cholesterol; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Gene Expression; Heat-Shock Proteins; Liver; Male; Mice; Mice, Inbred ICR; Non-alcoholic Fatty Liver Disease; Tetracycline; Transcription Factor CHOP; Triglycerides