[Study on the mechanism of action of total saponins of Panax notoginseng in ameliorating oxidative stress and insulin resistance in rats fed with high fat diet].

OBJECTIVE: To investigate whether total saponins of Panax notoginseng (tPNS) can ameliorate oxidative stress and insulin resistance (IR) in the high fat induced nonalcoholic fatty liver disease (NAFLD) rat model and to explore the relationship between oxidative stress and IR.

METHODS: Totally 50 healthy rats were randomly divided into the normal control group (NC), the model group, the high dose tPNS group (at the daily dose of 160 mg/kg), the low dose tPNS group (at the daily dose of 80 mg/kg), and the bicyclol group (at the daily dose of 100 mg/kg), 10 in each group. Rats in the NC group were fed with standard forage. Those in the rest group were fed with high fat forage. Distilled water was given by gastrogavage to those in the NC group and the model group. Corresponding medication was performed for 4 weeks. Four weeks later Lee's index and body weight were measured. All rats were sacrificed to detect the wet weight of livers. Their sera was isolated and detected to calculate liver functions (serum ALT and AST levels). Levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitive index (ISI) and insulin resistance index (IRI) were calculated. Serum levels of TNF-alpha and malondialdehyde (MDA), contents of total superoxide dismutase (T-SOD), hydroxy radical level (-OH), and total antioxidant capacity (T-AOC) were measured. Pathological changes of livers was observed by HE staining of paraffin section.

RESULTS: Compared with the NC group, rats' wet liver weight and Lee's index increased in the model group (P < 0.05), and results of light microscopy showed that obvious fatty degeneration occurred in livers. Compared with the model group, rats' wet liver weight and Lee's index, as well as ALT and AST could be obviously improved by tPNS and bicyclol (P < 0.05, P < 0.01). The fatty deposition of liver cells could also be alleviated. Compared with the NC group, serum levels of-OH, MDA, and TNF-alpha significantly increased, and activities of T-SOD and T-AOC decreased in the model group (P < 0.01), also accompanied with IR. Compared with the model group, concentrations of -OH, MDA, and TNF-alpha decreased after treated by tPNS (P < 0.05, P < 0.01), activities of T-SOD and T-AOC got recovered (P < 0.05, P < 0.01), and IR got obvious improvement (P < 0.01).

CONCLUSION: The anti-oxidative stress effect and IR improving effect of tPNS might play partial roles in treating NAFLD.