Mechanistic Investigation of the Iridoid Fraction from Morinda officinalis in the Treatment of Aging-Related Sarcopenia via the PI3K/Akt/mTOR Signaling Pathway

• • 60% ethanol heated reflux extraction yielded the highest iridoid content, with H103 macroporous resin and water elution achieving optimal purification; this scalable protocol ensures consistent enrichment of bioactive monotropein and deacetylasperulosidic acid for industrial production. • • In D-galactose-induced C2C12 myotube atrophy, the iridoid fraction significantly restored MYHC expression (P < 0.001) and promoted differentiation (P < 0.05–0.001), indicating direct myogenic potential that could translate to improved muscle regeneration in sarcopenic patients. • • In accelerated aging mice, treatment increased limb grip strength and hindlimb muscle mass-to-body weight ratio (P < 0.05–0.001) and expanded muscle fiber cross-sectional area in tibialis anterior and gastrocnemius (P < 0.01–0.001), demonstrating efficacy across both fast- and slow-twitch muscles, a critical advantage over therapies targeting only one fiber type. • • Mechanistically, the fraction upregulated PI3K/Akt/mTOR pathway proteins and genes (PIK3CA, AKT1, mTOR) (P < 0.05–0.001), while PI3K inhibitor LY294002 abolished these effects (P < 0.05), confirming pathway dependence and highlighting a druggable target for sarcopenia management.