Integrated LC-MS/MS, in vitro, and in silico approaches reveal the anticancer potential of the endemic Anatolian species Salvia hypargeia Fisch. & C.A. Mey
European Journal of Integrative Medicine, cilt.87, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 87
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.eujim.2026.102712
- Dergi Adı: European Journal of Integrative Medicine
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE
- Anahtar Kelimeler: Apoptosis, Cytotoxic activity, Molecular docking, Molecular dynamics simulations, Rosmarinic acid, Salvia hypargeia
- İnönü Üniversitesi Adresli: Evet
Özet
Introduction: The genus Salvia has a long history of use in traditional medicine for the treatment of various ailments, including inflammatory disorders, infections, and cancer-related conditions. Salvia hypargeia Fisch. & C.A.Mey. is an endemic Anatolian species; however, its anticancer potential has not been systematically investigated. The present study aimed to evaluate the phytochemical composition and anticancer-related in vitro and in silico properties of S. hypargeia extracts. Methods: Ethanol, methanol, and chloroform extracts were prepared from the aerial parts of S. hypargeia, with extraction yields of 7.38%, 10.93%, and 6.41%, respectively. Phenolic profiling was performed by LC-MS/MS. Cytotoxic activity was evaluated in MCF-7 human breast cancer and C6 rat glioma cells using the MTT assay, while SH-SY5Y cells were included as a comparator cell line. Apoptosis and cell cycle distribution were assessed by flow cytometry. Molecular docking and 250 ns molecular dynamics simulations were conducted to investigate the interactions of the major detected compounds with caspase-3 and caspase-7. Results: LC-MS/MS analysis identified rosmarinic acid as the predominant phenolic constituent in all extracts, with the highest level detected in the methanol extract (9.3998 mg/g extract), followed by the ethanol (9.2399 mg/g extract) and chloroform (2.6877 mg/g extract) extracts. Among the tested samples, the methanol extract showed the strongest and most selective cytotoxic activity against C6 glioma cells (IC₅₀ = 51.8 ± 1.45 µg/mL; SI = 1.38). Flow cytometric analysis demonstrated an increase in late apoptotic cells and accumulation in the S phase. In silico analysis indicated that rosmarinic acid showed the most favorable docking score toward caspase-3 (−9.343 kcal/mol) and maintained stable interactions during molecular dynamics simulations. Conclusions: Salvia hypargeia extracts showed preliminary in vitro cytotoxic and apoptosis-associated effects, particularly in C6 glioma cells. Rosmarinic acid was the major detected phenolic constituent and may contribute to the observed activity. However, compound-specific bioactivity testing and direct mechanistic experiments are required before identifying it as the principal active compound or establishing a definitive caspase-mediated mechanism.