Network Pharmacology Combined With Metabonomics and Transcriptomics Reveals the Mechanism of Rubus Chingii Hu in Alleviating Nephrotoxicity Caused by Tripterygium Glycosides Tablet

ABSTRACT

Researches on Tripterygium glycosides tablets (TGT) often overlook renal toxicity from prolonged use. Rubus chingii Hu (RCH) is beneficial to kidney health and has an unclear role in reducing nephrotoxicity. This study used UHPLC‐Q Exactive HFX to identify Kaempferol, Hydroxygenkwanin, and Luteolin as key active components of RCH. Network pharmacology revealed RCH could protect the kidneys by modulating TNF, IL‐17, NF‐kappa B, and JAK–STAT pathways through targets such as BCL2, CASP3, TNF, SIRT1, EGFR, and MMP9. Biochemical and pathological studies show that TGT induces kidney injury in rats, while RCH improves kidney function and reduces inflammation and oxidative stress. Western blot confirmed that RCH could regulate the expression of TNF‐α, cleaved caspase‐3, and SIRT1 proteins. Transcriptomics and metabonomics reveal significant enrichment in metabolic pathways like glycerophospholipid metabolism and inflammation signaling pathways such as PPAR and JAK–STAT. After RCH treatment, most differential genes remain stable, but all 20 key metabolites are restored. Further analysis indicates that steroid hormone biosynthesis and the PPAR signaling pathway are vital for RCH's protective effects, as it regulates CYP1B1, CYP4A1, CYP4A3, EHHADH, HMGCS2, and PPARG genes, alleviating TGT‐induced nephrotoxicity.