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Antiviral activity of a polysaccharide from Radix Isatidis (Isatis indigotica Fortune) against hepatitis B virus (HBV) in vitro via activation of JAK/STAT signal pathway

作者 Wang, Tianbao; Wang, Xinwei; Zhuo, Ya; Si, Changyun; Yang, Lu; Meng, Lijun; Zhu, Bin

期刊 JOURNAL OF ETHNOPHARMACOLOGY , JUL 15 2020,:257

DOI 10.1016/j.jep.2020.112782 PubMed 32217096

摘要 Ethnopharmacological relevance: Hepatitis B virus (HBV) infection frequently results in both acute and chronic hepatitis and poses serious threats to human health worldwide. Despite the availability of effective HBV vaccine and anti-HBV drugs, apparently inevitable side effects and resistance have limited its efficiency, thus prompt the search for new anti-HBV agents. The traditional Chinese medicine Radix Isatidis has been used for thousands of years, mainly for the treatment of viral and bacterial infection diseases including hepatitis.Aim of the study: In this study, antiviral activities of a Radix Isatidis (Isatis indigotica Fortune) polysaccharide (RIP) were evaluated in vitro model using the HepG2.2.15 cell line and the underlying mechanism was elucidated with the aim of developing a novel anti-HBV therapeutic agent.Materials and methods: Structure features of the purified polysaccharide RIP were investigated by a combination of chemical and instrumental analysis. Drug cytotoxicity was assessed using the MIT assay. The contents of HBsAg, HBeAg, intracellular and extracellular IFN-alpha level were measured using respective commercially available ELISA kit. The HBV DNA expression was evaluated by real-time quantitative polymerase chain reaction (PCR) and the relevant proteins involved in TFN/JAK/STAT signaling pathways were examined by western blot assay.Results: MTT assay showed that RIP had no toxicity on HepG2.2.15 cell line below the concentration 400 mu g/ml at Day 3, 6 and 9. Furthermore, RIP at the concentration of 50, 100 and 200 mu g/ml significantly reduced extracellular and intracellular level of HBsAg, HBeAg and HBV DNA in HepG2.2.15 cells in a time and dosedependent manner. Moreover, RIP also enhanced the production of IFN-alpha in HepG2.2.15 cell via activation of JAK/STAT signal pathway and induction of antiviral proteins, as evidenced by the increased protein expression of p-STAT-1, p-STAT-2, p-JAK1, p-TYK2, OAS1, and Mx in HepG2.2.15 cells. In addition, the over expression of SOCS-1 and SOCS-3 was significantly abolished under same conditions.Conclusions: These results suggested that the HBV inhibitory effect of RIP was possibly due to the activation of IFN-alpha-dependent JAK/STAT signal pathway and induction of the anti-HBV protein expression.

涉及物种 菘蓝 Isatis indigotica