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

Yacine Aouiffat, Boulanouar Bakchiche, Farouk Benaceur, Mounir M Bekhit, Mohamed M Salem, Mohamed Abbas Ibrahim, Soumia Moujane, Aziz Bouymajane, Imadiddine Kadi, Fathi Berrabah, Hicham Gouzi, Sanaa K Bardaweel, Ashok K Shakya, Mosad A Ghareeb

Journal: Scientific reports 2025;15(1):33887

PMID: 41027999

Free Full Text on Nature Publishing Group View on PubMed

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.

Address: Laboratory of Biological and Agronomic Sciences (LBAS), Amar Telidji University, Laghouat, 03000, Algeria.; Laboratory of Biological and Agronomic Sciences (LBAS), Amar Telidji University, Laghouat, 03000, Algeria. [email protected].; Research Unit of Medicinal Plant (RUMP) Attached to Center of Biotechnology (CRBt, 3000, Constantine), Laghouat, 03000, Algeria. [email protected].; Laboratory of Biological and Agronomic Sciences (LBAS), Amar Telidji University, Laghouat, 03000, Algeria.; Research Unit of Medicinal Plant (RUMP) Attached to Center of Biotechnology (CRBt, 3000, Constantine), Laghouat, 03000, Algeria.; Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.; College of Medicine, Huazhong University of Science and Technology, Wuhan, China.; Faculty of Medicine and Pharmacy of Guelmim, Ibn Zohr University, Guelmim, Morocco.; Biology, Environment and Health Team, Faculty of Sciences and Technologies, Moulay Ismail University, Errachidia, Morocco.; Team of Microbiology, and Health, Laboratory of Chemistry-Biology Applied to the Environment, Faculty of Sciences, Moulay Ismail University, Zitoune, Meknes, Morocco.; Research Unit of Medicinal Plant (RUMP) Attached to Center of Biotechnology (CRBt, 3000, Constantine), Laghouat, 03000, Algeria.; Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman, 11942, Jordan.; Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, 19328, Jordan.; Medicinal Chemistry Department, Theodor Bilharz Research Institute Kornaish El Nile, Warrak El-Hadar, (P.O. 30), Imbaba, Giza, 12411, Egypt. [email protected].

DOI: 10.1038/s41598-025-07975-7

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https://doi.org/10.1038/s41598-025-07975-7

Miscellaneous:

https://assays.cancer.gov/CPTAC-76

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-EGFR-11

MeSH Terms: Plant Leaves, Plant Extracts, Humans, Antioxidants, Molecular Docking Simulation, Phenols, Seasons, Cistus, Flavonoids, Cell Proliferation, Cell Line, Tumor, Algeria, Polyphenols, A549 Cells, ErbB Receptors, Computer Simulation