RT Journal Article
SR Electronic
T1 Swertiamarin Attenuates Experimental Rat Hepatic Fibrosis by Suppressing Angiotensin II-Angiotensin Type 1 Receptor-ERK Signaling
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.116.234179
DO 10.1124/jpet.116.234179
A1 Li, Shu
A1 Wang, Qinglan
A1 Tao, Yanyan
A1 Liu, Chenghai
YR 2016
UL http://jpet.aspetjournals.org/content/early/2016/08/19/jpet.116.234179.abstract
AB The rennin-angiotensin system (RAS) is crucial in hepatic fibrosis development, and therapies targeting this system may be a promising treatment for hepatic fibrosis. In this study, we investigated the effects of swertiamarin (Swe), an ethanol extract of Gentiana manshurica Kitag, on hepatic fibrosis and its underlying mechanisms through regulating RAS. Primary rat hepatic stellate cells (HSCs) were isolated and treated with angiotensin II (Ang II) with or without Swe and losartan. The proliferation and activation of HSCs were measured. Rat hepatic fibrosis was induced by intraperitoneal dimethylnitrosamine (DMN) injection for 4 weeks. Rats were treated with Swe or losartan from the 3rd week until the end of the experiment. Hydroxyproline (Hyp) content in liver tissue was assayed with Jamall's method and liver collagen deposition was visualized using sirius red staining. RAS components were analyzed by western blot, immunofluorescent staining, and real time RT-PCR. The results showed that Swe significantly inhibited Ang II-induced HSCs proliferation and activation. Swe also significantly suppressed DMN-induced alpha-smooth muscle actin production in rat liver and improved liver function. Swe partially inhibited Ang II-induced angiotensin type 1 receptor (AT1R) upregulation and suppressed Ang II-induced ERK and c-jun phosphorylation in HSCs. In the DMN-treated rats, Swe treatment significantly inhibited the plasma Ang II levels. DMN-induced AT1R upregulation and phosphorylation of ERK and c-jun in rat liver were also inhibited by Swe. In conclusion, Swe may attenuate hepatic fibrosis through inhibiting HSC activation by regulating the RAS.