Abstract
Hepatic fibrosis represents an important event in the progression of chronic liver injury to cirrhosis, and is characterized by excessive extracellular matrix proteins aggregation. Early fibrosis can be reversed by inhibiting hepatocyte injury, inflammation, or hepatic stellate cells activation, so the development of antifibrotic drugs is important to reduce the incidence of hepatic cirrhosis or even hepatic carcinoma. Here we demonstrate that Schisandrol B (SolB), one of the major active constituents of traditional hepato-protective Chinese medicine, Schisandra sphenanthera, significantly protects against hepatocyte injury, while Wedelolactone (WeD) suppresses the TGF-β1/Smads signaling pathway in hepatic stellate cells (HSCs) and inflammation, the combination of the two reverses hepatic fibrosis in mice and the inhibitory effect of the combination on hepatic fibrosis is superior to that of SolB or WeD treatment alone. Combined pharmacotherapy represents a promising strategy for the prevention and treatment of liver fibrosis.
Highlights
Hepatic fibrosis is caused by chronic injury and persistent excessive inflammation, which is accompanied with chronic HBV or HCV infection, alcoholic steatohepatitis, NASH, and biliary diseases (Cordero-Espinoza and Huch, 2018)
Clinical studies have confirmed that LWWL has definite therapeutic effects on liver fibrosis, we demonstrated that LWWL could attenuate hepatic fibrosis via modulation of TGF-β1 and NF-κB signaling pathways in bile duct ligation (BDL) and CCL4-induced hepatic fibrosis rat models (Liu et al, 2018a; Liu et al, 2018b)
We demonstrate that Schisandrol B (SolB), WeD or the combination of SolB and WeD could reverse hepatic fibrosis in vivo and the inhibitory effect of combination of SolB and WeD on hepatic fibrosis is superior to that of SolB or WeD treatment alone
Summary
Hepatic fibrosis is caused by chronic injury and persistent excessive inflammation, which is accompanied with chronic HBV or HCV infection, alcoholic steatohepatitis, NASH, and biliary diseases (Cordero-Espinoza and Huch, 2018). Hepatic fibrosis is a key process in the development of chronic injury to cirrhosis, eventually leading to liver failure and even hepatocellular carcinoma with a worldwide mortality. Once chronic injury or persistent inflammation is resolved, hepatic fibrosis can be regressed (Bansal and Chamroonkul, 2019). Treatment of hepatic fibrosis is important for the prevention of cirrhosis and related diseases. Many potential therapeutic drugs including chemicals and biological drugs have been developed to prevent and treat hepatic fibrosis (Fagone et al, 2016; Schuppan et al, 2018), but there is still a lack of effective antifibrotic drugs in clinic.
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