A standardized combination of Sphaeranthus indicus and Mangifera indica extracts improves antioxidant defense and anabolic signaling and attenuates dexamethasone-induced skeletal muscle atrophy.

BACKGROUND: Skeletal muscle atrophy is characterized by impaired protein synthesis, increased proteolysis, oxidative stress, and mitochondrial dysfunction. Phytoceutical interventions with antioxidant and cytoprotective properties may offer therapeutic potential in muscle-wasting conditions. OBJECTIVE: To assess the effects of LI12542F6 SMI, a standardized formulation of Sphaeranthus indicus (SI) flower heads and Mangifera indica (MI) bark extracts (2:1), on dexamethasone (DEX)-induced skeletal muscle atrophy and to elucidate the underlying molecular mechanisms. DESIGN: In vitro studies assessed antioxidant activity, endothelial nitrite production, protein synthesis, and the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling (PI3K/AKT/mTOR) pathway, with or without DEX. In vivo, male Sprague Dawley rats received DEX (0.1 mg/kg body weight) and were supplemented with SMI (0, 45, or 90 mg/kg body weight) for 12 days. Outcomes included lean body mass, grip strength, muscle histology, antioxidant enzyme activity, and the expression of anabolic and catabolic protein markers. RESULTS: SMI enhanced reactive oxygen species scavenging and increased endothelial nitrite production via PI3K/AKT-mediated activation of endothelial nitric oxide synthase. In DEX-treated rats, SMI attenuated declines in lean body mass, grip strength, and muscle fiber morphology. Mechanistically, SMI improved antioxidant markers, activated PI3K/AKT/mTOR signaling and myogenic markers, and suppressed catabolic and apoptotic proteins. The hepatic or renal biochemical parameters were unaltered. DISCUSSION: These findings indicate that SMI mitigates glucocorticoid-induced muscle atrophy through coordinated modulation of oxidative stress, mitochondrial function, and anabolic signaling pathways. The activation of PI3K/AKT/mTOR signaling appears central to its effects, linking antioxidant activity with enhanced protein synthesis and the suppression of apoptotic signaling. CONCLUSIONS: SMI attenuates DEX-induced skeletal muscle atrophy and improves functional and molecular markers. These findings suggest further investigation and clinical substantiation of this phytoceutical as a possible intervention for muscle-wasting conditions.