Notoginsenoside R1, An Active Compound from Panax notoginseng, Inhibits Hepatic Stellate Cell Activation and Liver Fibrosis via MAPK Signaling Pathway

Activation of the hepatic stellate cell is implicated in pathological vascularization during development of liver fibrosis. MAPK signaling is involved in the activation of hepatic stellate cell. Oxidative stress and inflammation are also involved in the pathogenesis of liver fibrosis. Notoginsenoside R1 is an effective saponin isolated from the roots of Panax notoginseng (Burk) F. H. Chen and exerts anti-oxidant, anti-inflammatory and anti-fibrotic roles in various diseases. However, the role of Notoginsenoside R1 in liver fibrosis has not been investigated yet. First, a rat model with liver fibrosis was established through oral gavage administration with carbon tetrachloride. Data from hematoxylin and eosin (H&E) and Masson's trichrome stainings showed that carbon tetrachloride induced severe hepatic damages, including inflammatory cell infiltration, lipid droplets deposition in hepatocytes and liver centrilobular necrosis. Meanwhile, the rats were also intraperitoneal injected with different concentrations of Notoginsenoside R1. Results demonstrated that Notoginsenoside R1 treatment suppressed the pathological changes in the livers with enhanced levels of ALB and TP, and reduced levels of ALP, AST and ALT. Second, Notoginsenoside R1 also significantly attenuated carbon tetrachloride-induced decrease in PPAR-[Formula: see text] and increase in Coll-a1, [Formula: see text]-SMA and TIMP1 in liver tissues ([Formula: see text][Formula: see text] 0.001). Third, the decrease in GSH, SOD and GST and increase in MDA, IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] induced by carbon tetrachloride were markedly restored by Notoginsenoside R1 ([Formula: see text][Formula: see text] 0.001). Lastly, Notoginsenoside R1 counteracted with the promotive effects of carbon tetrachloride on levels of proteins involved in MAPK signaling, including phosphorylated p65 (p-p65), p-ERK, p-JNK and p-p38. In conclusion, Notoginsenoside R1 suppressed the activation of hepatic stellate cells and exerted anti- oxidant and anti-inflammatory to attenuate carbon tetrachloride-induced liver fibrosis through inactivation of NF-[Formula: see text]B and MAPK signaling.