Network Pharmacology-Based Strategy to Explore the Effect and Mechanism of Zhizhu Granule Improving Glucose-Lipid Metabolism in Rats with Metabolic Syndrome

Jiali Wang,1,2 Yiqing Liu,3 Chengkui Xiu,1 Xue Wang,1 Yinan Liu,1 Yanhong Hu,1 Jing Yang,1 Yan Lei1 1Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 3National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yan Lei; Jing Yang, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Tel +13651217893 ; +15901070286, Email 13651217893@163.com; yangjingdr@163.comObjective: To explore the mechanism of the traditional Chinese medicine (TCM), Zhizhu granule (ZZG), in treating metabolic syndrome (MS) based on network pharmacology and pharmacodynamic experiment.Materials and Methods: Network pharmacology combined with a pharmacodynamic experiment was used to elucidate the therapeutic mechanism of ZZG in MS. Serum samples were collected from rats with MS, induced by a high-sugar-fat-salt diet (HSFSD) combined with streptozotocin (STZ), to measure the levels of biochemical markers. The glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were detected. The liver tissue of rats was used for histological examination and Western blot analysis.Results: Network pharmacology analysis generated 69 drug-disease common targets and 10 hub genes closely related to ZZG against MS. KEGG pathway analysis revealed that the PI3K/AKT signaling pathway was the most potential pathway, which took part in the therapeutic mechanisms. In the animal experiments section, the therapeutic effect of ZZG on MS and the therapeutic pathway of ZZG on MS were verified. ZZG could significantly decrease the body weight, TC, TG, LDL-C and GLU levels in MS rats (all p< 0.01), alleviate hepatocyte steatosis and decrease liver lipid droplet deposition. Western blot analysis indicated that compared with the model group, the expression levels of PI3K, AKT, and IRS-1 protein were significantly increased (all p< 0.05), and the FOXO-1 was significantly decreased (all p< 0.05) in the ZZG group.Conclusion: ZZG can improve glucose-lipid metabolism disorder in rats with metabolic syndrome. The reported results provide experimental evidence for ZZG in the treatment of MS.Keywords: metabolic syndrome, network pharmacology, Zhizhu granule, pharmacodynamic experiment, PI3K/AKT pathway