Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1/PI3K/AKT signaling pathway in type 2 diabetic mice

• Published in: Frontiers in endocrinology (Lausanne) 2022-12, Vol.13, p.1068555
• Main Authors: Mao, Yong-Po, Song, Yi-Ming, Pan, Sheng-Wang, Li, Ning, Wang, Wen-Xiang, Feng, Bin-Bin, Zhang, Jian-Hai
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Cholesterol - adverse effects; Codonopsis - metabolism; Codonopsis Radix and Polygonati Rhizoma; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - metabolism; Endocrinology; hypoglycemic; Mice; pathology section; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; type 2 diabetes mellitus; western blotting
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2022.1068555

Codonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism. A T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT. Compared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) ( 0.01 and 0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group ( 0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR ( 0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups ( 0.05). H&E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3β, PI3K, p-Akt and p-FOXO1( 0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (