Seasonal variation in the phenolic compounds of Algerian Cistus creticus leaf extracts: an in silico and in vitro study

Abstract

This study investigates the seasonal influence on the phenolic and flavonoid composition of Cistus creticus leaf extracts and evaluates their antioxidant and antiproliferative properties through experimental and computational methods. The results showed that samples collected in September exhibited significant antioxidant activity, with IC50 values of 127.44 µg/mL and 108.62 µg/mL in the ABTS and molybdenum assays, respectively. In comparison, samples collected in March displayed higher IC50 values of 139.67 µg/mL (ABTS) and 166.51 µg/mL (molybdenum), indicating reduced antioxidant potency. Additionally, the extracts demonstrated strong antiproliferative effects against two cancer cell lines, with the March sample exhibiting the highest total polyphenol content (113.42 mg GAE/g) and the greatest efficacy against A549 cells (IC50 = 11.9 µg/mL). Molecular docking results indicated that the myricetin-EGFR complex was stabilized by five hydrogen bonds and had a binding energy of -9 kcal/mol. Similarly, the myricetin-NADPH oxidase complex showed seven hydrogen bonds and an identical binding energy of -9 kcal/mol. The stability of these complexes was further validated through 100-ns molecular dynamics simulations. Overall, these findings underscore the therapeutic potential of C. creticus leaf extracts as natural antioxidant and anticancer agents.