Sarcopenia-induced muscle loss has a significant societal impact on older people and progressively increases frailty and disability. The anabolic hormone insulin growth factor-1 (IGF-1) is a key growth hormone for muscle growth by inducing protein synthesis while catabolic muscle RING-finger protein-1 (MuRF-1) has been identified as E3 ubiquitin ligases and mediated proteolysis. The present study aimed to screen Angiotensin Receptor Blockers (ARBs) binding affinity to specified proteins through an in-silico approach. Out of eight ARBs, azilsartan and telmisartan exhibited good affinity to IGF-1 and MuRF-1 proteins. Then lead ARB, azilsartan (AZL) was further investigated in High-Fat Diet (HFD)-induced sarcopenia-associated muscle loss in the rat model. Male Sprague Dawley rats, 4 and 14 months were used as young and old, respectively, and divided into control and treatment. The control group was treated with vehicles and azilsartan treatment. Old rats were further fed with HFD for 4 months and served HFD-induced old rats. Further, HFD-induced sarcopenic rats were divided into the old control and AZL-treated old group. AZL was given at the dose of 8 mg/kg, per oral for 6 weeks. After treatment, rats were analyzed for functional muscle tests and results showed that AZL significantly increased muscle coordination and locomotor activities in sarcopenic rats.

Sarcopenia, azilsartan, antioxidants, High fat diet, skeletal muscle.