Phytochemical profiling and bioactivity of Rhaponticoides mykalea : α ‐glucosidase inhibition, apoptosis‐associated cytotoxicity, and in silico molecular insights

Abstract BACKGROUND Rhaponticoides mykalea is an endemic species with limited data on its phytochemistry and biological activity. The aqueous ethanol extract (700 mL L −1 , v/v) of the aerial parts and its n ‐hexane, ethyl acetate ( RPEtAc ), n ‐butanol, and water fractions were evaluated for enzyme inhibition, antioxidant activity, cytotoxicity, and apoptosis‐related effects, together with LC – HRMS profiling and molecular docking/ MM ‐ GBSA analysis. RESULTS Among the samples, RPEtAc showed the highest total phenolic (273.49 ± 3.80 mg GAE  g −1 ) and flavonoid (175.45 ± 2.53 mg CE g −1 ) contents and the strongest DPPH , FRAP , and CUPRAC activities. It was the most active α ‐glucosidase inhibitor ( IC 50  = 128.78 ± 2.57 μg mL −1 ), exceeding acarbose (209.21 ± 1.32 μg mL −1 ) under the assay conditions, and the most cytotoxic fraction toward RL95 ‐2 endometrial cancer cells ( IC 50  = 15.35 ± 0.68 μg mL −1 , 48 h), increasing caspase‐3 and caspase‐9 activities and the Bax/Bcl‐2 ratio. LC – HRMS identified phenolic acids (chlorogenic, vanillic, ferulic, and 3‐(4‐hydroxyphenyl)propionic acids) and flavonoid derivatives. In silico , flavonoid glycosides detected in RPEtAc (quercetin 3‐rutinoside 7‐glucoside, narcissin, isoquercitrin) showed favorable predicted MM ‐ GBSA binding at the BCL ‐2 BH3 groove, and quercetin, narcissin, and rutin at the α ‐glucosidase site. CONCLUSION The ethyl acetate fraction of R. mykalea aerial parts is a phenolic‐rich fraction with antioxidant, α ‐glucosidase inhibitory, and apoptosis‐associated cytotoxic activity demonstrated at the fraction level. The docking results provide computational support only and require experimental validation with isolated compounds. © 2026 Society of Chemical Industry.