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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01438

Bicyclol attenuates liver inflammation induced by infection of hepatitis C virus via repressing ROS-mediated activation of MAPKs/NF-κB signaling pathway

 Zong-Gen Peng1*,  Hu Li1, Jian-Rui Li1,  Meng-Hao Huang1, Jin-Hua Chen1, Xiao-Qin Lv1, Li-Li Zou1, Jia-Li Tan1, Biao Dong1 and Jian-Dong Jiang1
  • 1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, China

Treatment with direct-acting antivirals (DAAs) cures most patients infected with hepatitis C virus (HCV) in the real world. However, some patients, especially those with underlying advanced liver disease, have a limited reduction of liver injury after achieving a sustained viral response (SVR). Bicyclol was widely used in clinic for the treatment of a variety of liver injuries but with an unknown mechanism for the treatment of hepatitis C. We investigated the anti-inflammatory effects and mechanisms of bicyclol in HCV-infected hepatocytes and further confirmed the putative results in mouse hepatitis model induced by the co-injection of polyinosinic-polycytidylic acid [poly (I:C)] and D-galactosamine (D-GalN). The results showed that the activation of nuclear factor kappa B (NF-κB) and subsequent increase of inflammatory factors were directly induced by HCV infection and were persistent after clearance of the virus in Huh7.5 cells. Bicyclol decreased the activation of NF-κB and the levels of inflammatory factors in HCV-infected hepatocytes by inhibiting the activation of the ROS-MAPKs-NF-κB pathway, and the effect was synergistic with DAAs in HCV-infected hepatocytes. Bicyclol attenuated the ROS/MAPKs/NF-κB axis via recovering mitochondrial function without a dependence on dihydronicotinamide adenine dinucleotide phosphate oxidase and superoxide dismutases. The anti-inflammatory effects and mechanism of bicyclol were verified in mouse hepatitis induced by the co-injection of poly(I:C)/D-GalN. Conclusion: Bicyclol directly ameliorates the chronic inflammation caused by HCV infection and might be used with DAAs or after DAA therapy for ultimately curing chronic hepatitis C.

Keywords: Hepatitis C virus, Bicyclol, anti-inflammatory therapy, Inflammatory factor, Oxidative Stress

Received: 11 Aug 2018; Accepted: 21 Nov 2018.

Edited by:

Ying Yu, Shanghai Institutes for Biological Sciences (CAS), China

Reviewed by:

Mingxiang Zhang, Shandong University, China
Qiang Deng, Fudan University, China  

Copyright: © 2018 Peng, Li, Li, Huang, Chen, Lv, Zou, Tan, Dong and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zong-Gen Peng, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, 100050, Beijing Municipality, China,