Abstract
Background/Objectives:Taraxacum officinale F.H.Wigg. (Asteraceae), an edible plant and commonly used Chinese herbal medicine, has significant anti-inflammatory and antioxidant effects in the form of its root water extract (TRWE). Therefore, this study was designed to elucidate the principal pharmacological effects and underlying mechanisms of water extract from Taraxacum roots (TRWE) against cisplatin-induced nephrotoxicity through an integrated approach combining network pharmacology and experimental validation. Methods: Mechanistic prediction was performed using network pharmacology, molecular docking, and GeneMANIA-based functional analysis, followed by experimental validation via H&E staining, TUNEL, biochemical assays (blood urea nitrogen, BUN; creatinine, CRE; malondialdehyde, MDA; superoxide dismutase, SOD; and catalase, CAT), and Western blotting. Results: Network pharmacology identified 52 kidney injury-associated targets of Taraxacum. Functional enrichment analysis indicated their roles in apoptosis and endoplasmic reticulum stress, particularly through the PERK-mediated UPR pathway, suggesting the PERK/eIF2α/ATF4 axis as a potential key regulatory node. Animal experiments suggested that 100, 200, and 400 mg/kg inhibited cisplatin-induced increases in BUN, CRE, and MDA; restored SOD/CAT levels; and alleviated kidney apoptosis and endoplasmic reticulum stress via the PERK/eIF2α/ATF4 pathway. Molecular docking suggested strong binding of phytochemicals (caftaric acid, CTA; chlorogenic acid, CGA; caffeic acid, CA; and cichoric acid, CCA) to PERK, eIF2α, and ATF4. Conclusions: This study predicts that the PERK/eIF2α/ATF4 signaling pathway may be a critical mediator of TRWE's potential renoprotective effects against cisplatin-induced acute kidney injury, offering a potential theoretical basis for further mechanistic exploration.