Mechanistic Investigation of the Iridoid Fraction from Morinda officinalis in the Treatment of Aging-Related Sarcopenia via the PI3K/Akt/mTOR Signaling Pathway
Aging-related sarcopenia remains a clinical challenge due to limited effective interventions. This study systematically evaluated the therapeutic potential of the iridoid fraction from Morinda officinalis and elucidated its mechanism via the PI3K/Akt/mTOR pathway. Using monotropein and deacetylasperulosidic acid as markers, extraction was optimized with 60% ethanol under heated reflux, yielding the highest iridoid content. Purification employed H103 macroporous resin with water as eluent, achieving maximal recovery. In vitro, the fraction significantly ameliorated D-galactose-induced C2C12 myotube atrophy (P < 0.001) and promoted myotube differentiation (P < 0.05, 0.01, 0.001), as evidenced by MYHC expression. In vivo, D-galactose-accelerated aging mice treated with the fraction exhibited increased limb grip strength and hindlimb muscle mass-to-body weight ratio (P < 0.05, 0.01, 0.001), along with expanded cross-sectional area of tibialis anterior and gastrocnemius muscles (P < 0.01, 0.001). Transcriptomic and network pharmacology analyses implicated the PI3K/Akt pathway. Western blotting and qRT-PCR confirmed upregulation of key proteins and genes (PIK3CA, AKT1, mTOR) in the pathway (P < 0.05, 0.01, 0.001), while the PI3K inhibitor LY294002 reversed these effects (P < 0.05). These findings demonstrate that the iridoid fraction from M. officinalis mitigates aging-related sarcopenia through PI3K/Akt/mTOR signaling, providing a promising candidate for clinical translation.