Bicyclol for chronic hepatitis C

Yang, Xiaoyan; Zhuo, Qin; Wu, Taixiang; Liu, Guan Jian

doi:10.1002/14651858.cd004994.pub2

Cited by 6 publications

(9 citation statements)

References 17 publications

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“…Results showed that the blood HCV viral load went down after treating with bicyclol, consistent with the previous observations. Liver enzymes declined significantly as well, agreeing with previous reports1., 6.. The maximum concentration of bicyclol is about 123.87 μg/L (0.32 μmol/L) in healthy adult plasma after oral administration of bicyclol at 50 mg, tid for 7 days 43 , and our in vitro results also showed anti-HCV activity under this concentration (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Three months treatment with bicyclol caused no damage to liver, kidney and bone marrow function in the patients. In fact, bicyclol decreased blood level of liver enzymes, consistent with its activity of liver protection3., 6.. Bicyclol was approved by the Chinese FDA as a hepatoprotective drug, and in the past decade bicyclol has been proved to be effective and safe in clinic 1 .…”

Section: Discussionmentioning

confidence: 83%

“…Previous clinical observations showed that HCV RNA level decreased in hepatitis C patients after bicyclol mono-therapy1., 6.. In these previous Phase IV clinical trials, the hepatitis C patients were treated with bicyclol after failure to the interferon-alpha plus ribavirin therapy.…”

Section: Discussionmentioning

confidence: 99%

“…In a phase IV clinical trial in China, chronic hepatitis C (CHC) patients who have failed to the standard therapy (interferon- α plus ribavirin) were enrolled to receive bicyclol treatment. After 6-month treatment with bicyclol, both HCV RNA and liver transaminases levels decreased in the patients1., 6.. However, the mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Huang

Xue

et al. 2019

Acta Pharmaceutica Sinica B

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Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Huang

Xue

et al. 2019

Acta Pharmaceutica Sinica B

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“…Classical antioxidants, such as glutathione (GSH)[63], N-acetyl cysteine (NAC)[133] and vitamin E[130], have been reported to treat hepatitis C with efficacy. In addition, bicyclol (4,4’-dimethoxy-5,6,5’,6’-bis(methylenedioxy)-2-hydroxymethyl-2’-methoxycarbonyl biphenyl), a synthetic compound derived from schizandrin C extracted from the Chinese medicinal herb Fructus schisandrae , has potent antioxidative and certain anti-HCV effects in the clinic with safety[134,135]. Clinically, bicyclol tablets are used in many countries to treat various non-viral hepatitis and chronic hepatitis B and C accompanied by mild and moderate serum aminotransferase abnormality.…”

Section: Anti-inflammatory/hepatoprotective Therapy In Hcv Infectionmentioning

confidence: 99%

Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy

Li¹,

Huang²,

Jiang³

et al. 2018

WJG

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Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

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Pharmacological treatments for chronic hepatitis C liver disease: a network meta-analysis

Gurusamy

Toon²,

Thorburn

et al. 2015

Cochrane Database of Systematic Reviews

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Bicyclol for chronic hepatitis C

Cited by 6 publications

References 17 publications

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication

Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy

Pharmacological treatments for chronic hepatitis C liver disease: a network meta-analysis

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