Establishing Molecular Mechanism of Carnosine Against Hypobaric Hypoxia Induced Muscle Protein Loss via In‐Silico and In‐Vivo Approach

Skeletal muscle is highly susceptible to hypobaric hypoxia linked muscle protein loss due to disturbed proteostasis and redox homeostasis. Carnosine, an endogenous dipeptide possesses antioxidant, anti-inflammatory, anti-glycation and pH buffering properties. The present study investigated the beneficial efficacy of carnosine in amelioration of muscle protein loss during chronic hypobaric hypoxia exposure in rats. Further, probable molecular mechanism for it's protective efficacy was also established via molecular docking study along with support of in-vivo study. Male Sprague-Dawley rats were divided into three groups: Control (unexposed rats), HH (07d hypobaric hypoxia exposed rats), HH + CAR (Carnosine supplement rats with 07d hypobaric hypoxia exposure 50 mg/kg supplemented). Carnosine administration downregulated myostatin expression levels while IGF-1 level was upregulated and this was accompanied with an increase in total protein content. The expression levels of FOXO, MAFbx, MuRF1, markers of muscle atrophy were also declined on carnosine supplementation. Further, myogenesis markers, myoG, and mTOR were found increased in carnosine supplemented rats. Along with these activities, carnosine also managed excessive reactive oxygen species (ROS) production, protein oxidation and damage. Ergo, molecular docking study supported the fact that carnosine has the ability to bind with IGFBP and myostatin, a negative regulator of muscle atrophy. Carnosine attenuates muscle protein loss via enhancing myogenesis, managing redox, and protein homeostasis. All these activities together enhances protein concentration and ameliorates hypobaric hypoxia induced muscle protein loss. Therefore, carnosine supplementation can be an effective therapeutic strategy in combating skeletal muscle protein loss linked with high altitude induced hypobaric hypoxia.