Uncovering key bioactive fatty acids from velvet antler extracts that promote healthspan and neuroprotection in Caenorhabditis elegans

BACKGROUND Velvet antler has been traditionally recognized for its multifaceted health benefits, yet the underlying pharmacological mechanisms have remained poorly understood. RESULTS In this study, we employed advanced analytical techniques, including liquid chromatography–mass spectrometry and gas chromatography, coupled with a Caenorhabditis elegans model, to elucidate the active small-molecule components and their associated bioactivities. Our results demonstrate that a methanol-derived velvet antler extract significantly extended the lifespan of C. elegans , enhanced physical functions such as pharyngeal pumping and body bends, and protected against toxic protein aggregation in models of Parkinson's disease (α-synuclein), Huntington's disease (polyQ), and Alzheimer's disease (Aβ). Through systematic fractionation and bioactivity-guided assays, we identified stearic acid (C18:0), linoleic acid (C18:2n), and arachidonic acid (C20:4n) as key fatty acids responsible for these health-promoting effects. Notably, a mixture of these three fatty acids at optimal concentrations conferred healthspan benefits and neuroprotection comparable to the complete extract. CONCLUSION These findings provide novel insights into the pharmacological potential of velvet antler and highlight specific fatty acids that could serve as promising therapeutic agents for aging and neurodegenerative disorders. © 2025 Society of Chemical Industry.