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

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 (IC50 = 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 (IC50 = 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.