Celastrol and Cblin peptide activation of IGF-1 signaling prevents microgravity-induced atrophy in rat L6 myotubes

This study investigated the efficacy of two natural compounds-celastrol, a heat shock protein (HSP) inducer, and Cblin peptide, a ubiquitination inhibitor-in counteracting muscle atrophy under real microgravity conditions. Both agents independently attenuated microgravity-induced reductions in myotube thickness, myosin heavy chain protein levels, and atrogene expression. Celastrol primarily enhanced HSP expression, whereas Cblin peptide inhibited insulin receptor substrate-1 degradation, thereby promoting insulin-like growth factor-1 signaling. Despite their distinct molecular actions, no synergistic or additive effects were observed when combined. These findings highlight the potential of celastrol and Cblin peptide as functional ingredients for mitigating muscle atrophy, particularly in the context of space travel. Notably, Cblin peptide is abundant in glycinin-rich soybean protein, and celastrol is derived from the root of <i>Tripterygium wilfordii</i> (Taiwan vine). Future applications may include incorporating these plant-derived compounds into space foods to improve the quality of life for astronauts in space.<b>NEW & NOTEWORTHY</b> This study evaluated the effects of celastrol and the Cblin peptide in mitigating muscle atrophy under microgravity conditions. Both compounds alleviated myotube atrophy through distinct mechanisms, though no synergistic effect was observed. Celastrol upregulated heat shock protein (HSP) expression, whereas Cblin prevented IRS-1 degradation, thereby enhancing IGF-1 signaling. Sourced from <i>Tripterygium wilfordii</i> and soybean protein, respectively, these agents may serve as functional space foods to help counteract muscle atrophy and support astronauts' health during spaceflight.