Two iridoid compounds isolated from Rhododendron pachypodum flowers — compound 5 (a newly characterized analogue) and compound 8 (a known iridoid) — extended Caenorhabditis elegans lifespan by up to 30.4% and 30.8% respectively across multiple doses, surpassing the positive control β-nicotinamide mononucleotide (NMN) at 25.4% (all P < 0.001). Beyond longevity, both compounds improved pharyngeal pumping rate and locomotion, while compound 8 boosted oxidative stress survival by 41.1%. Compound 5 additionally enhanced heat-stress tolerance and early reproductive output. Seven of the nine isolated iridoids were previously undescribed, with absolute configurations confirmed via TD-DFT-calculated ECD spectra.
Iridoids are a structurally diverse class of monoterpene glycosides found in plants like olives, blueberries, and gentian — with established anti-inflammatory and neuroprotective properties — but their direct longevity-modulating potential has been undercharacterized. Outperforming NMN, one of the most commercially hyped longevity supplements, is an attention-grabbing benchmark, though the comparison is informative rather than definitive. The critical caveat: C. elegans is a powerful initial screening model but shares only partial metabolic and physiological homology with mammals. Lifespan extensions in worms frequently fail to translate to rodent or human biology. No mechanistic pathway — whether DAF-16/FOXO, SKN-1/Nrf2, or mTOR — is identified here, which limits interpretive depth. Still, the combination of novel chemical characterization, in vivo multi-metric healthspan assessment, and a culturally contextualized ethnobotanical source makes this a solid foundational study warranting mechanistic follow-up in mammalian models.
