Ethanol extract of Pharbitis nil ameliorates liver fibrosis through regulation of the TGFβ1-SMAD2/3 pathway

Pharbitis nil (L.) Choisy is a medicinal herb, and herbal remedies based on its seeds have been used to treat of obesity and liver diseases, including fatty liver and liver cirrhosis in East Asia.Liver fibrosis is a major cause of morbidity and mortality in patients with chronic liver inflammation such as that caused by non-alcoholic steatohepatitis. However, no effective pharmaceutical treatment for liver fibrosis has been approved. In this study, we aimed to investigate that ethanol extract of pharbitis nil (PNE) alleviates the liver fibrosis.We studied the effects of PNE on two preclinical models. Six-week-old male C57BL/6 mice were intraperitoneally injected with CCl4 twice weekly for 6 weeks and then treated with 5 or 10 mg/kg PNE daily from week 3 for weeks. Secondly, mice were fed HFD for 41 weeks and at 35 weeks treated with 5 mg/kg PNE daily for the remaining 6 weeks. In addition, we examined the antifibrotic effects of PNE in primary mouse hepatic stellate cells and LX-2 cells.PNE treatment ameliorated hepatocyte necrosis, inflammation, and liver fibrosis in CCl4-treated mice and inhibited the progression of liver fibrosis in mice with HFD-induced fibrosis. PNE reduced the expressions of fibrosis markers and SMAD2/3 activations in mouse livers and in TGFβ1-treated primary mouse hepatic stellate and LX-2 cells CONCLUSIONS: This study demonstrates that PNE attenuates liver fibrosis by downregulating TGFβ1-induced SMAD2/3 activation.