Network Pharmacology and Experimental Analysis to Explore the Effect and Mechanism of Modified Buyang Huanwu Decoction in the Treatment of Diabetic Nephropathy

Fan Yang,1,* Limin Pan,2,* Xiaoyun Zhang,1,* Jiaan Huang,3 Yan Liu,3 Peixuan Li,3 Yuehua Wang1,3,4 1College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050091, People’s Republic of China; 2First Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050033, People’s Republic of China; 3College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Hebei University of Chinese Medicine & Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, Hebei, 050091, People’s Republic of China; 4Second Affiliated Hospital, Hebei University of Chinese Medicine, Hebei, 073000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuehua Wang, Email [email protected]: Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN.Patients and Methods: Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD.Results: A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson’s staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1.Conclusion: mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.Keywords: diabetic nephropathy, network pharmacology, molecular docking, traditional Chinese medicine