Aras_2026_Cytotech_78_180

Gundelia komagenensis Firat, an endemic member of the Asteraceae family, was investigated for its phytochemical composition, antioxidant, enzyme inhibitory, cytotoxic, and computationally predicted pharmacological properties. Methanol (MeOH) and dichloromethane (DCM) extracts prepared from the aerial parts of Gundelia komagenensis were evaluated using ABTS and FRAP antioxidant assays, enzyme inhibition tests against acetylcholinesterase (AChE), alpha-glucosidase, and alpha-amylase, LC-MS/MS profiling, MTT-based cytotoxicity assays, and integrated in silico analyses. Both extracts exhibited antioxidant activity; among the extracts, DCM had a lower ABTS IC50 value than MeOH (13.7 vs.14.5 microg/mL). DCM also had lower IC50 values for AChE, alpha-glucosidase, and alpha-amylase than MeOH (1.132-1.372 microg/mL). LC-MS/MS revealed solvent-dependent profiles, with chlorogenic acid, vanillin, trans-cinnamic acid, and gentisic acid predominating in MeOH, and vanillin, trans-cinnamic acid, and luteolin in DCM. The MeOH extract of G. komagenensis did not exhibit significant cytotoxicity against either MIA PaCa-2 or HUVEC cells. In contrast, the DCM extract reduced MIA PaCa-2 cell viability in a concentration-dependent manner while exerting relatively limited effects on HUVEC cells, suggesting a selective cytotoxicity tendency under the tested conditions. Computational analyses identified chlorogenic acid as the most promising bioactive constituent. Molecular docking showed the highest binding affinities toward AChE, alpha-glucosidase, and alpha-amylase, while molecular dynamics simulations and MM-GBSA calculations supported the stability of the corresponding protein-ligand complexes. Network pharmacology suggested that the identified phenolics may regulate disease-related pathways through AP-1/NF-kappaB-associated targets. Chlorogenic acid emerged as a key multi-target candidate warranting further experimental validation.