Abstract
OBJECTIVE: This study investigates the pharmacokinetic interactions and anticancer potential for rosuvastatin in combination with Momordica charantia (M. charantia) extract through both in vitro and in vivo models. METHODS: A validated high-performance liquid chromatography (HPLC) method (R² = 0.9983) was used to quantify rosuvastatin plasma levels. In vivo pharmacokinetic parameters were assessed in Wistar rats following oral administration of rosuvastatin, M. charantia extract, and their combination. In vitro, HepG2 liver cancer cells were treated with rosuvastatin, M. charantia, and their combination to evaluate anticancer activity. The half-maximal inhibitory concentration (IC₅₀) and fractional inhibitory concentration (FIC) were calculated to assess cytotoxic effects and interaction profiles. RESULTS: The IC₅₀ values were 231.7 µg/mL for M. charantia, 59.1 µg/mL for rosuvastatin, and 48.7 µg/mL for the combination, with an FIC index of 1.03, indicating additive effects. The combination enhanced anticancer efficacy by promoting apoptosis, modulating oxidative stress, and altering lipid and cholesterol metabolism in HepG2 cells. In vivo, co-administration of M. charantia significantly shortened rosuvastatin's half-life and increased its elimination rate, without affecting the maximum plasma concentration (Cmax) or the area under the plasma concentration-time curve (AUC). CONCLUSION: These findings suggest that M. charantia may influence rosuvastatin pharmacokinetics and enhance its anticancer effects. The study supports the potential of combining natural products with conventional pharmaceuticals as adjunctive therapies in cancer treatment while highlighting the need for further clinical investigation.