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

Abstract

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.