Abstract: Objective To observe the effect of Shenbing Decoction III for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking. Methods Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction III group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction III against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets. Results Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction III treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction III were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction III had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction III obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue. Conclusion Shenbing Decoction III can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1.

Key words: Shenbing Decoction III; 5/6 nephrectomy; renal fibrosis; network pharmacology; molecular docking techniques