Diabetes, Metabolic Syndrome and Obesity (Jul 2021)
Qihu Preparation Ameliorates Diabetes by Activating the AMPK Signaling Pathway in db/db Mice
Abstract
Hongfang Zeng,1– 3,* Xiaoli Li,1– 3,* Duanfang Zhou,1– 3 Ning Wang,4 Xiaoping Yu,1– 3 Liangyuan Long,1,3 Hao Cheng,5,6 Shuyu Zhou,5 Zhengze Shen,7 Weiying Zhou1– 3 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Drug Metabolism, Chongqing, People’s Republic of China; 3Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 4West China Biopharm Research Institute, West China Hospital, Chengdu, Sichuan Province, 610041, People’s Republic of China; 5China Company 18th, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 6Department of Pharmacy, Medical Security Center, the 925 Hospital, Joint Logistic Support Force, Guiyang, Guizhou Province, 550005, People’s Republic of China; 7Department of Pharmacy, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiying ZhouDepartment of Pharmacology, College of Pharmacy, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel/Fax +86 23 684 85161Email [email protected]: To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice.Materials and Methods: Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses.Results: Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice.Conclusion: The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.Keywords: type 2 diabetes mellitus, T2DM, Traditional Chinese medicine, TCM, TXNIP, anti-inflammatory