YIMITI Nadila, LIU Mengwen, BAI Tianya, PENG Xing, DUAN Shuyan, XIAO Hui, SHEN Jing
The medicinal mushroom Inonotus obliquus has long been used in traditional medicine for metabolic disorders; however, the therapeutic potential of its crude polysaccharides(C-IOPS）against insulin resistance and glucose-lipid metabolic disturbances remains unexplored. To study the ameliorative effects of C-IOPS in insulin resistant rats with glucose and lipid metabolism disorder, an insulin resistant rat model was established using a high-fat diet combined with alloxan induction. After 5 days of adaptive feeding, the rats were randomly divided into six groups(n=10 per group): blank control group, model group, positive control group(metformin, 107 mg·kg-1·d-1), and three C-IOPS-treated groups at low(100 mg·kg-1·d-1), medium(200 mg·kg-1·d-1), and high(400 mg·kg-1·d-1）doses. Rats in the blank control group received no gavage, while those of the model group were administered 2.5 mL distilled water by gavage. The positive control group received 2.5 mL metformin hydrochloride solution at a dose of 107 mg·kg-1, and the low-, medium-, and high-dose C-IOPS groups were administered 2.5 mL C-IOPS solution at doses of 100, 200, and 400 mg·kg-1, respectively, by gavage once daily. Blood glucose, serum parameters, and hepatic inflammatory cytokines were measured. Liver tissue morphology, structure, and pathological features were examined by histology. Protein expression levels of protein kinase B(AKT), phosphorylated AKT(p-AKT), glycogen synthase kinase-3β(GSK-3β), and phosphorylated GSK-3β(p-GSK-3β）in liver tissue were determined by Western blotting, and the ratios of p-AKT/AKT and p-GSK-3β/GSK-3β were calculated. The results showed that after three days of intervention, compared with the model group, the positive control group and all C-IOPS groups exhibited significant increased body weight, and elevated hepatic p-AKT/AKT and p-GSK-3β/GSK-3β ratios. Fasting blood glucose, 0.5-h postprandial glucose, the area under the glucose curve, triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and hepatic proinflammatory cytokines including interleukin-1β(IL-1β), IL-6, and tumor necrosis factor-α(TNF-α）were significantly decreased. Compared with the model group, the positive control group and high-dose C-IOPS group showed significantly reduced 2-h blood glucose and alanine aminotransferase(ALT）activity, while the positive control group and medium- and high-dose C-IOPS groups exhibited significantly decreased aspartate aminotransferase(AST）activity. Histopathological analysis showed that C-IOPS attenuated hepatocellular edema and hepatic steatosis. These findings suggest that the beneficial effects of C-IOPS are mediated, at least in part, through the AKT and GSK-3β signaling pathways. Our study provides evidence that crude polysaccharides from I. obliquus hold promise as a dietary intervention for ameliorating insulin resistance and glucose-lipid metabolic disorders.
