Network pharmacology and experimental investigation of the protective effect of Shuxuetong injection against diabetic nephropathy and encephalopathy in db/db mice

Objective: To investigate the protective effects and mechanism of Shuxuetong injection on diabetic nephropathy and encephalopathy in db/db mice by integrating animal experiments and network pharmacology. Materials and methods: Thirty 4-week-old male db/db mice with type 2 diabetes were divided into model group and Shuxuetong injection group, and the age-matched db/m group was the control group after 16 weeks of feeding. In this study, Shuxuetong injection tail intravenous injection (2 mL/kg) lasted for 2 weeks form 16th to18th, and the whole experimental period was two weeks.Systematic network pharmacology involves the identification of active components and targets. Finally, we used ELISA to verify the inflammatory factors affected by the core pathway. Results: Histopathological analysis showed that Shuxuetong injection reducing hypertrophy of kidney tissues and basement membrane, as well as improving learning and memory impairment and decreasing hippocampal neuronal apoptosis induced by diabetes. It also significantly reduced blood urea nitrogen and creatinine levels as well as urinary microalbumin excretion rates.We found the core pathway was the “AGE-RAGE signaling pathway in diabetic complications”. This map showed that the pathway could affect the expression of inflammatory factors such as MCP-1, IκBα. ELISA demonstrated that Shuxuetong injection suppressed the expression of MCP-1 (P < 0.05).Moreover, Shuxuetong injection could inhibit the expressions of IκBα, increase the expressions of Akt, thereby effectiveiy alleviate the diabetic nephropathy. Conclusions: By studying pharmacodynamics and the analyzing of network pharmacology, the protective effect of Shuxuetong injection on diabetic nephrotic encephalopathy was preliminarily verified, and the possible targets and pathways were predicted, providing valuable evidence for further exploration of the therapeutic mechanism of Shuxuetong injection in capillaries.