Skeletal muscle atrophy, which involves the loss of skeletal muscle function, can be triggered by pathological factors such as disuse, cancer cachexia, and aging. This condition is characterized by decreased muscle fiber size, reduced myonuclear count, and subsequent weakening of muscle strength accompanied by depletion of contractile proteins. Imbalances in anabolic hormones, elevated levels of transforming growth factor β, myostatin, cytokines (such as tumor necrosis factor-alpha, TWEAK, and interleukin-6), oxidative stress, and limited availability of amino acids further contribute to the progression of muscle atrophy. To date, there are no FDA-approved drugs available for skeletal muscle atrophy. In this study, we conducted molecular docking using HR-LCMS-QTOF identified garlic compounds (375) against key targets involved in skeletal muscle atrophy, including histone deacetylase 4, Nuclear factor kappa-light-chain-enhancer of activated B cells, Atrogin, Murf1, mammalian target of the rapamycin, Myostatin, insulin like growth factor-1, and Beclin. These targets play crucial roles in the mechanism of skeletal muscle atrophy. Among the 375 compounds analyzed, austalide A exhibited the highest binding affinity with all targets. The current study findings provide a base for continued exploration of these natural compounds in the development of skeletal muscle atrophy therapeutics.
Key words: molecular docking, ligand receptor interactions, skeletal muscle atrophy, Austalide A, natural compounds
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