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Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl 4 . In addition, the RAW264.7 macrophages were cultured in the presence of CoCl 2 to simulate a hypoxic microenvironment of fibrotic livers in vitro . The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl 4 -induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro . Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

Liver fibrosis, a common pathological process in chronic liver diseases, is characterized by excessive accumulation of extracellular matrix proteins and considered as a wound healing response to chronic liver injury. Hepatic stellate cell (HSC) activation plays a key role in liver fibrosis development. Previous studies showed that sulforaphane (SFN) has wide protective effects against tissue injury and inflammation. Accumulating evidence has shown that microRNAs play important roles in the development of hepatic fibrosis, some of which have been identified as potential therapeutic targets. This study was conducted to explore the role of SFN in the suppression of HSC activation. Quantitative real-time PCR showed that HSC miR-423-5p levels were up-regulated during HSC activation and down-regulated after SFN administration. Further, transfection of a miR-423-5p mimic demonstrated that inhibition of HSC activation by SFN required down-regulation of miR-423-5p. We showed that suppressor of fused is the direct target of miR-423-5p. SFN may play a role in inhibiting hepatic fibrosis by downregulating miRNA-423-5p. MiRNA-423-5p may be useful as a therapeutic target for treating hepatic fibrosis.

Objective: To investigate the mechanism underlying the protective effects of a traditional Chinese medicinal formula, Baoganning, against liver fibrosis., Methods: Male Wistar rats were subjected to injection of carbon tetrachloride- peanut oil mixture and given daily 5% alcoholic beverage, and 2 days after the injection, Baoganning was administered intragastrically at two different doses for 6 weeks. Radioimmunoassay was used to detect serum leptin level, and immunohistochemistry employed to examine the effect of Baoganning on expressions of leptin and its receptor in the liver tissue of the rats., Results: Compared with the normal control group, the rats in the liver fibrosis model group and Baoganning-treated groups showed significantly increased serum leptin levels (P<0.01), and the serum leptin level was significantly lower in Baoganning group than in the liver fibrosis model group (P<0.01). Baoganning significantly reduced the hepatic expression of leptin and OB-Rb in rats with liver fibrosis in comparison with their expression in the model group (P<0.01)., Conclusion: Baoganning can effectively ameliorate liver fibrosis in rats possibly through reducing serum leptin level and inhibiting hepatic leptin and its receptor expressions.