Degenerative diseases, particularly neurodegenerative disorders, pose significant global health challenges. Traditional medicine systems offer valuable leads for novel therapeutic development. This ethnopharmacological study investigated Keumiki leaf (Glochidion spp), a traditional medicinal plant from Aceh Province, Indonesia, as a therapeutic candidate for degenerative diseases. Comprehensive ethnobotanical surveys revealed high recognition (89.3%) of Keumiki for treating cognitive impairment, inflammatory conditions, and age-related disorders. Phytochemical analysis demonstrated rich composition with total phenolic content of 347.0 ± 4.12 mg GAE/g and total flavonoid content of 163.2 ± 2.78 mg QE/g in ethanol extract. Antioxidant assays revealed potent activity with DPPH IC₅₀ of 23.45 μg/mL, comparable to standard antioxidants. Molecular mechanism studies using Western blot and RT-PCR demonstrated significant activation of the Nrf2/HO-1 antioxidant pathway (2.3-fold and 1.8-fold increases, respectively) and suppression of pro-inflammatory pathways, including downregulation of NF-κB, TNF-α, IL-1β, and IL-6. Strong correlations between phytochemical content and biological activities (r > 0.87) suggest phenolic and flavonoid compounds as primary contributors to therapeutic effects. This integrated ethnopharmacological approach validates traditional knowledge and provides scientific evidence supporting Glochidion spp as a promising therapeutic candidate for degenerative diseases through dual antioxidant and anti-inflammatory mechanisms.
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