Aydin_2025_Food.Sci.Nutr_13_e70749

The hypothesis that insulin resistance and impaired insulin-like growth factor signaling contribute to Alzheimer's disease (AD) has led to the designation of AD as "type 3 diabetes." Ajuga chamaepitys subsp. chia is traditionally used in Trkiye as an analgesic, tonic, and for the external treatment of hemorrhoids and wound healing. This study evaluates antioxidant, antidiabetic, and anticholinesterase activities of methanolic, aqueous extracts, and essential oils from the flowering aerial parts of A. chamaepitys subsp. chia, along with their phytochemical profiles (GC-MS/MS), morphological-anatomical characteristics, and molecular docking analysis. The essential oil yield was 0.002%, comprising 45 compounds (92.5%), with beta-pinene (19.8%), alpha-pinene (12.8%), and germacrene D (10.0%) as major constituents, dominated by monoterpene (39.8%) and sesquiterpene hydrocarbons (23.5%). The methanolic extract exhibited moderate bioactivity, achieving 28.36% alpha-amylase inhibition at 5000 microg/mL and 21.85% acetylcholinesterase inhibition at 100 microg/mL, while also demonstrating notable antioxidant activity with 23.013% ABTS(+) and 8.114% DPPH() scavenging. It showed the highest total phenolic (14.261 microg GAE/mg) and tannin content (34.444 microg TAE/mg) among the tested extracts. Morphologically, the plant features hairy stems and tripartite leaves with a cuticle, trichomes, and diacytic stomata, while anatomically, it presents collenchyma, starch-filled parenchyma, and a distinct cambium in the stem. Molecular docking studies revealed that germacrene D exhibited strong binding affinities to acetylcholinesterase, butyrylcholinesterase, alpha-amylase, and alpha-glucosidase, suggesting multitarget inhibition potential. These findings support the traditional use of A. chamaepitys subsp. chia and highlight its promise as a natural source for therapeutic agents targeting oxidative stress, diabetes, and neurodegenerative diseases.