Therapeutic potential of p-cymene in mitigating alcohol-induced damage in umbilical cord-derived mesenchymal stem cells through restoration of Nanog, VEGF, and antioxidants levels; in silico and in vitro approaches.

Abstract

Human stem cells can divide and differentiate into various cell types. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are multipotent cells with high regenerative, anti-inflammatory, and immunomodulatory properties. Ethanol, the main component of alcoholic beverages, induces cytotoxicity and oxidative stress in cells. In recent years, natural compounds have gained attention for their potential protective effects against ethanol-induced cellular damage. p-Cymene is one such compound that acts as an antioxidant. This study aimed to evaluate the potential of p-cymene to reduce the harmful effects of alcohol on ethanol-induced cytotoxicity and oxidative stress in UC-MSCs through in silico and in vitro approaches. In silico pharmacokinetic and toxicity analyses of p-cymene were used, followed by in vitro evaluation using ethanol-injured UC-MSCs. Cell viability, antioxidant [glutathione (GSH), super-oxide dismutase (SOD)], inflammatory, proliferative, apoptotic, and wound healing assays were performed across different concentrations to assess protective effects. The pharmacokinetic analysis showed that p-cymene exhibited considerable pharmacokinetic properties by following Lipinski's Rule of Five. Toxicity analysis revealed no toxic effects of p-cymene, suggesting its potential as a natural compound. Further in vitro experimentation showed that p-cymene independently restored cell viability, reduced inflammation, stabilized Nanog, improved vascular endothelial growth factor (VEGF), enhanced antioxidants (GSH, SOD), promoted wound healing, and reduced cell death in ethanol-injured cells, with the 50 µM concentration being the most effective. These findings support our hypothesis that p-cymene protects UC-MSCs from ethanol-induced damage.