Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti‐fibrosis effect by inhibition of mammalian target of rapamycin

A previous study has demonstrated that Ganshuang granule ( GSG ) plays an anti‐fibrotic role partially by deactivation of hepatic stellate cells ( HSC s). In HSC s activation, mammalian target of rapamycin ( mTOR )‐autophagy plays an important role. We attempted to investigate the role of mTOR ‐autophagy in anti‐fibrotic effect of GSG . The cirrhotic mouse model was prepared to demonstrate the anti‐fibrosis effect of GSG . High performance liquid chromatography ( HPLC ) analyses were used to identify the active component of GSG . The primary mouse HSC s were isolated and naringin was added into activated HSC s to observe its anti‐fibrotic effect. 3‐methyladenine (3‐ MA ) and Insulin‐like growth factor‐1 ( IGF ‐1) was added, respectively, into fully activated HSC s to explore the role of autophagy and mTOR . GSG played an anti‐fibrotic role through deactivation of HSC s in cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC analyses and naringin markedly suppressed HSC s activation in vitro , which suggested that naringin was the main active component of GSG . The deactivation of HSC s caused by naringin was not because of the autophagic activation but mTOR inhibition, which was supported by the following evidence: first, naringin induced autophagic activation, but when autophagy was blocked by 3‐ MA , deactivation of HSC s was not attenuated or reversed. Second, naringin inhibited mTOR pathway, meanwhile when mTOR was activated by IGF ‐1, deactivation of HSC s was reversed. In conclusion, we have demonstrated naringin in GSG suppressed activation of HSC s for anti‐fibrosis effect by inhibition of mTOR , indicating a potential therapeutic application for liver cirrhosis.