Yiqi–Wenyang–Tiaoshen Decoction Reduces Cisplatin‐Induced Acute Kidney Injury in Rats Through Autophagy and Apoptosis Signaling Pathways Based on Network Pharmacology and Experimental Validation

CONTEXT: The mechanism of Yiqi-Wenyang-Tiaoshen decoction (YWT) in treating cisplatin-induced acute kidney injury (AKI) remains unknown. OBJECTIVE: This study identifies the key components of YWT and explores its therapeutic potential and mechanisms in a cisplatin-induced AKI rat model. MATERIALS AND METHODS: UPLC-ESI-MS/MS was utilized for the identification of compounds present in both the aqueous extract of YWT and serum samples. The overlapping components were recognized as active constituents, followed by a network pharmacological analysis. A rat model of cisplatin-induced AKI was established, and comprehensive pathological analyses including HE, PAS, and electron microscopy, as well as biochemical assessments of serum Cre, BUN, IL-6, and TNF-α levels, were conducted. Western blotting was utilized to evaluate the expression levels of Caspase-3, Caspase-9, BAX, Bcl-2, and LC3 Ⅱ/Ⅰ. RESULTS: Using UPLC-ESI-MS/MS, we identified 182 compounds in the aqueous extract of YWT, 34 of which are confirmed to be absorbable into the bloodstream. Network pharmacological analysis suggests that YWT primarily acts by inhibiting apoptosis and activating autophagy. In the rat model, YWT significantly ameliorated renal pathology and electron microscopic features. Additionally, YWT mitigated body weight loss and renal hypertrophy while lowering serum creatinine and blood urea nitrogen levels. YWT alleviates AKI by suppressing apoptosis-related proteins such as Caspase-3, Caspase-9, and BAX, enhancing Bcl-2 expression, increasing the LC3 Ⅱ/Ⅰ ratio, and reducing p62, a marker of autophagy. DISCUSSION AND CONCLUSION: This study confirms the therapeutic efficacy of YWT in cisplatin-induced AKI, potentially linked to its ability to inhibit apoptosis, activate autophagy, and mitigate mitochondrial damage.