Cudrania tricuspidata Leaf-Derived Polysaccharides Attenuate Cisplatin-Induced Cytotoxicity in HEK 293T Cells via the Nrf2/HO-1 Pathway

Prolonged administration of cisplatin, a widely used chemotherapeutic agent, induces nephrotoxicity. Identifying natural compounds that attenuate cisplatin’s adverse effects on renal tissues would be of clinical value. Thus, the present study aimed to evaluate the cytoprotective effects of Cudrania tricuspidata leaf-derived polysaccharides (CTP) in human embryonic kidney (HEK) 293T cells to explore their potential as a chemotherapeutic adjuvant. In the cell viability assay, CTP alone showed no inherent cytotoxic effects, whereas co-treatment with cisplatin led to a significant improvement in cell viability. These observations were corroborated by Annexin V/propidium iodide staining, which demonstrated that CTP effectively attenuated cisplatin-induced cell damage in HEK 293T cells. CTP also increased the total antioxidant capacity in the 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and ferric reducing antioxidant power assays in a dose-dependent manner while elevating the activities of intracellular antioxidant enzymes, including catalase and superoxide dismutase, which correlated with the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. Moreover, CTP reduced malondialdehyde levels, indicating that it protected against oxidative-stress-induced membrane damage. Mechanistically, CTP mitigated cisplatin-induced apoptosis by upregulating B cell lymphoma 2 (Bcl-2) expression while suppressing the expression of Bcl-2-associated X protein, cleaved caspase-3, and caspase-9. Collectively, the findings demonstrate that pretreatment with CTP protected HEK 293T cells from cisplatin-induced damage, highlighting its potential as a functional food ingredient.