Mechanism Of Radix Pseudostellariae Polysaccharide Through The Nrf2 Pathway To Improve Hepatic IR

AIM:To study the role of Radix Pseudostellariae Polysaccharide(RPP) in hepatic insulin resistance reduced by high fat diet and related mechanisms. METHODS: Six week-old C57BL/6J mice were randomly divided into low fat feeding control group(LFD) and high fat feeding model group(HFD). After 8 weeks, intraperitoneal pyruvate tolerance test(IPPTT) was performed to determine the establishment of the HFD-induced hepatic insulin resistance model. HFD containing RPP(500 mg/Kg) was given for 2 consecutive weeks. Then, IPPTT, liver malondialdehyde(MDA) and liver mitochondrial MDA levels were also measured. The levels of protein p-PKB( Ser 473/Thr 308), p-AMPK; nuclear factor E2 related factor 2(Nrf2), NQO1 and IκBα in the liver tissues were measured by Western blotting. The m RNA expression of Lactobacillus and Bifidobacterium of guts in each group determined by PCR RESULTS:After administration of RPP, a significant reduction in blood glucose levels and hepatic mitochondrial MDA level were observed. The levels of p-AKT Ser473/Thr 308 and p-AMPK were significantly enhanced in the liver tissue. The hepatic IκBα levels were up-regulated. RPP also enhanced the levels of Nrf2 system regulated proteins NQO1 and HO-1 in liver tissues. The m RNA expression of Lactobacillus and Bifidobacterium of guts in HFD+RPP group vs HFD group were increased,results were statistical significantly different. CONCLUSION:Radix Pseudostellariae Polysaccharides effectively reduces high-fat diet-induced hepatic insulin resistance in C57BL/6J mice and improves liver glucose metabolism by ameliorating high fat diet impaired hepatic transduction of insulin signaling, activating Nrf2 associated signaling,inhibiting the expression of inflammatory signaling proteins and increasing intestinal flora in guts.