The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of Nelumbo nucifera Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy
Eunji Park, Hojung Choi, Cao-Sang Truong, Hee‐Sook Jun
Abstract
leaf (NNL) ethanolic extract on muscle atrophy induced by dexamethasone (DEX), a synthetic glucocorticoid, in mice and its underlying mechanisms. The administration of NNL extract increased weight, cross-sectional area, and grip strength of quadriceps (QD) and gastrocnemius (GA) muscles in DEX-induced muscle atrophy in mice. The NNL extract administration decreased the expression of muscle atrophic factors, such as muscle RING-finger protein-1 and atrogin-1, and autophagy factors, such as Beclin-1, microtubule-associated protein 1A/1B-light chain 3 (LC3-I/II), and sequestosome 1 (p62/SQSTM1) in DEX-injected mice. DEX injection increased the protein expression levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), cleaved-caspase-1, interleukin-1beta (IL-1β), and cleaved-gasdermin D (GSDMD), which were significantly reduced by NNL extract administration (500 mg/kg/day). In vitro studies using C2C12 myotubes also revealed that NNL extract treatment inhibited the DEX-induced increase in autophagy factors, pyroptosis-related factors, and NF-κB. Overall, the NNL extract prevented DEX-induced muscle atrophy by downregulating the ubiquitin-proteasome system, autophagy pathway, and GSDMD-mediated pyroptosis pathway, which are involved in muscle degradation.