• S. argentea is particularly rich in fiber, β-carotene, vitamin C, and potassium. • Ethanolic extraction produced a phenolic-rich fraction with potent bioactivities. • The extract effectively inhibited key Alzheimer’s disease–related enzymes in vitro. • Metabolomics revealed associations with cholinergic and amyloidogenic pathways. • Molecular docking showed strong flavonoid binding to cholinesterases and BACE-1. A thorough nutritional and metabolomic analysis of the edible fern Selaginella argentea was conducted, using in vitro and network pharmacology evidence to determine its potential to prevent Alzheimer's disease (AD). S. argentea exhibited a high dietary fiber content (34.31±0.38 g/100 g) and was particularly rich in β-carotene (4,328.76±69.41 µg/100 g), vitamin C (1,152.72±72.57 mg/100 g), and potassium (3,090.73±188.38 mg/100 g), as determined on a dry weight basis . Minimal fat and heavy metal contamination also corroborated its potential as a functional food. A sequential solvent extraction by polarity index generated an ethanolic fraction that contained large amounts of phenolics, with high antioxidant activity primarily from flavonoids and phenolic acids. In vitro enzyme inhibition assays demonstrated potential activity against AD-associated enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE-1), implying its neuroprotective activity. These actions were corroborated by network pharmacology analyses, with a range of metabolites related to AD-associated molecular targets, including cholinergic, amyloidogenic, neuroinflammation, and oxidative stress pathways. Molecular docking also supported favorable binding of these flavonoids to cholinesterases and BACE-1. S. argentea showed promise as a candidate for functional foods, with nutritional analyses of targeted and non-targeted metabolomics supporting neurological health. In vitro bioactivity and bioinformatic modeling also provided a strong scientific foundation for the traditional use and future development of S. argentea products.
Kittibunchakul et al. (Sun,) studied this question.