Camellia Tea Saponin Ameliorates 5-Fluorouracil-Induced Damage of HaCaT Cells by Regulating Ferroptosis and Inflammation.

Background/objective: Ferroptosis is an iron-dependent form of programmed cell death characterized by lipid peroxidation products (LPOs). A chemotherapeutic drug, 5-fluorouracil (5-FU), can induce epithelial mucositis and favor drug synergism with erastin in ferroptosis. tea saponin extract (TS) is known to exert antioxidative properties. This study aims to delineate the protective role of TS in mitigating 5-FU-induced ferroptosis and inflammation in human keratinocytes.

Methods: HaCaT cells were induced by 5-FU and erastin, treated with different TS doses, and their viability was then determined. Levels of cellular reactive oxygen species (ROS), LPOs, labile iron pool (LIP), glutathione (GSH), glutathione peroxidase 4 (GPX-4) activity, as well as IL-6, IL-1β, and TNF-α levels, and their wound healing properties were assessed.

Results: TS per se (at up to 25 µg/mL) was not toxic to HaCaT cells but was unable to restore the viability of 5-FU-induced cells up to the baseline levels. The compound significantly diminished increases in cellular ROS, LPOs, and LIP, while restoring GSH content and GPX-4 activity. Additionally, it suppressed the cytokine production of 5-FU-induced cells in a concentration-dependent manner. Moreover, TS exerted wound-healing effects against skin injuries and 5-FU damage significantly and dose dependently.

Conclusions: The insights of this work have identified biochemical mechanisms using tea saponin extract to protect against 5-FU-induced keratinocyte ferroptosis and inflammation. This study highlights the promising adjunctive potential of tea saponin in the mitigation and management of chemotherapy-induced mucositis.