Echinophora tenuifolia L. subsp. sibthorpiana Modulates Stress Response and Mitochondrial Quality Under Glucose Stress in Caenorhabditis elegans

<i>Echinophora tenuifolia</i> L. subsp. <i>sibthorpiana</i> (<i>E</i>. <i>tenuifolia</i>), Apiaceae, is a traditional medicinal and culinary plant, yet its phytochemical composition and biological activity have not been fully investigated. The aim of the present study was to evaluate the chemical profile of <i>E. tenuifolia</i> aerial parts extract and to assess its effects on healthspan and metabolic regulation in <i>Caenorhabditis elegans</i> (<i>C</i>. <i>elegans</i>). The characterization of the extract by NMR spectroscopy and HPLC-PDA revealed the presence of secondary metabolites, with rutin being the most abundant phenolic compound identified in the extract, alongside the presence of chlorogenic acid, ferulic acid, rosmarinic acid, caffeic acid, <i>p</i>-coumaric acid, and salicylic acid. The extract supplementation enhanced early-life locomotor activity and chemosensory behavior without affecting the lifespan. It also significantly improved thermotolerance and resistance to oxidative stress in <i>C</i>. <i>elegans</i>. Additionally, in a glucose-induced obesity model, the extract reduced lipid accumulation and triglyceride levels and restored glucose-impaired mitochondrial membrane potential. The extract dose-dependently alleviated glucose-induced endoplasmic reticulum and mitochondrial stress by suppressing the expression of both essential chaperones: endoplasmic reticulum chaperone BiP homolog hsp-4 and heat shock protein hsp-6. These findings indicate that <i>E. tenuifolia</i> extract possesses potential beneficial effects on metabolic and mitochondrial health under glucose-induced stress conditions. These observations are likely mediated by the synergistic phenolic composition of the extract, and reveal <i>E</i>. <i>tenuifolia</i> as a promising source of bioactive compounds relevant to aging and preventive strategies for cardiometabolic health.