Amelioration of Liver Fibrosis by Pharbitis nil Through TGFβ1-SMAD2/3 Pathway

Abstract

In the regions of Eastern Asia, traditional remedies of the seeds of the medicinal herb Choisy, scientifically known as Pharbitis nil (L.) have been used to treat hepatic diseases such as cirrhosis of the liver, fatty liver, and obesity. In chronic inflammatory hepatic disorders such as non-alcoholic steatohepatitis, fibrosis of the liver is the leading cause of morbidity and mortality. However, efficacious pharmaceutical products to treat liver fibrosis are awaiting approval. Jung and colleagues investigated whether alleviation of hepatic fibrosis is possible with Pharbitis nil ethanolic extract (PNE). Two different pre-clinical models were used in this investigation. C57BL/6 male mice that were 6 weeks old were given CCl₄ as intraperitoneal injections two times a week for 6 weeks after which they were subjected to daily administration of 5 or 10 mg/kg PNE from the third week onwards. For 41 weeks the mice were given a high-fat diet (HFD) and at week 35 they were given 5mg/kg PNE every day for the final 6 weeks. The antifibrotic effects of PNE were further evaluated in primary mouse hepatic stellate cells and LX-2 cells. In both CCl4-treated mice and mice subjected to HFD, PNE successfully mitigated liver fibrosis, inflammation, and hepatic necrosis as well as inhibited the liver fibrosis progression. Reduced levels of fibrosis markers such as SMAD2/3 activations in mouse livers and in TGFβ1-treated primary mouse hepatic stellate and LX-2 cells show that PNE attenuates liver fibrosis by downregulating TGFβ1-induced SMAD2/3 activation. J Ethnopharmacol. 2022 Aug 10;294:115370.