Identification of active anti-aging ingredients from asparagus cochinchinensis based on the spectrum-effect relationship

Aging is an irreversible degenerative process marked by declining physiological function. Developing therapeutics to delay aging and prolong healthy life represents a significant research focus. The dried roots of Asparagus cochinchinensis (Lour.) Merr. (Asparagi Radix, AR), a traditional Chinese medicine, possesses various pharmacological properties, including antioxidative, antitumor, and anti-inflammatory effects, and is commonly used in anti-aging formulas. Although steroidal saponins are its major active components, the specific compounds responsible for its anti-aging effects remain unidentified, and their mechanistic basis is unclear. This study evaluated the anti-aging effects of AR-derived total saponin extracts (ATSE) in Caenorhabditis elegans and elucidated underlying mechanisms. We prepared multiple ATSE batches from distinct geographical sources and assessed their bioactivity through lifespan and healthspan analyses (brood size, pharyngeal pumping), stress resistance, assays (oxidative, thermal), senescence biomarkers (lipofuscin accumulation, SOD activity, ROS levels). Mechanistic insights were obtained using transgenic strains and qRT-PCR, while ELSD-HPLC fingerprinting and spectrum-effect correlation identified active compounds. Key findings demonstrated that ATSE from Sichuan (T1) most effectively prolonged C. elegans lifespan (p < 0.01), enhanced stress resistance, increased SOD activity, and decreased ROS levels. The lifespan extension was primarily mediated through the FOXO/DAF-16 signaling pathway, while spectrum-effect analysis further identified (25S)-officinalisnin-II as the most active compound, extending C. elegans longevity under oxidative stress by 13.91%. Our research revealed AR's anti-aging mechanism and identified a key active compound, laying the foundation for quality-controlled AR therapeutics and providing new insights for the development of anti-aging drugs from traditional Chinese medicine.