Abstract
Background: Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by progressive renal dysfunction and proteinuria. Suyin Detoxification Prescription (SDP), a traditional Chinese medicine (TCM) formulation, has shown promising clinical efficacy in alleviating DN symptoms. This study is aimed at comprehensively evaluating the therapeutic effects of SDP through clinical observations, network pharmacology analysis, and molecular mechanism exploration. Methods: This study employed a randomized controlled trial combined with network pharmacology, pathological analysis, immunofluorescence, and Western blot to comprehensively investigate the therapeutic efficacy and mechanisms of SDP in DN treatment. Results: Clinical data revealed that SDP significantly reduces serum creatinine levels (p = 0.009) and reduced proteinuria (p = 0.03) in DN patients. Network pharmacology successfully established an interaction network among active components of SDP, FXR targets, and DN pathological processes. Experimental validation demonstrated that the formula significantly downregulated TNF-α, gp91, and P-MLK1 expression in renal tissues of diabetic mice. Notably, FXR knockout markedly attenuated the renal protective effects of SDP in DN mice. Conclusion: SDP exerts renal protective effects in DN through FXR activation, mitigating oxidative stress and inflammatory damage, while reducing proteinuria and renal function impairment, providing novel therapeutic strategies for DN management.