Decoding the Pharmacological Secrets of Shenqi Dizhi membrane kidney formula attenuates membranous nephropathy: A network pharmacology and transcriptomics approach

Introduction: Idiopathic membranous nephropathy (IMN) is a challenging autoimmune kidney disease. Based on the traditional Chinese medicine (TCM) theory of "dual deficiency of qi and yin" and "blood stasis", our group developed Shenqi Dizhi Compound Formula (SQDZ). This study aimed to systematically investigate the pharmacological effects and underlying mechanisms of SQDZ in treating IMN. Methods: We integrated a passive Heymann nephritis (PHN) rat model with UPLC-MS/MS-based chemical profiling, network pharmacology, and renal transcriptomic analysis to identify the active components, potential targets, and mechanisms of SQDZ. Results: UPLC-MS/MS analysis identified 588 compounds in SQDZ, including active ingredients like baicalin and astragaloside II. Network pharmacology mapped these to 261 potential therapeutic targets. In PHN rats, SQDZ significantly reduced urinary protein, improved lipid metabolism, and alleviated renal injury. Mechanistically, it modulated immune-inflammatory pathways (e.g., IL-6/STAT3) and regulated complement and coagulation cascades (involving Serpine1 , F10 , Itgal ). It also restored podocyte function and reduced inflammation via downregulation of Ccr2 and Cd38 . Transcriptomics consolidated six core genes: Cd38 , F10 , Slc5a2 , Itgal , Ccr2 , and Serpine1 . Discussion: The findings indicate that SQDZ acts through synergistic, multi-targeted modulation of both immune-inflammatory and coagulation pathways, rather than a single target. This mechanism aligns well with the TCM principles of replenishing "qi and yin" and resolving "blood stasis," providing a systems-level explanation for its efficacy. Conclusion: This study demonstrates that SQDZ exerts multi-target therapeutic effects on IMN, providing a robust pharmacological basis for its clinical application.