The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy
Muscle atrophy is characterized by a decline in muscle mass and function. Excessive glucocorticoids in the body due to aging or drug treatment can promote muscle wasting. In this study, we investigated the preventive effect of <i>Nelumbo nucifera</i> leaf (NNL) ethanolic extract on muscl...
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MDPI AG
2023-02-01
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| Series: | Nutrients |
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| author | Eunji Park Hojung Choi Cao-Sang Truong Hee-Sook Jun |
| author_facet | Eunji Park Hojung Choi Cao-Sang Truong Hee-Sook Jun |
| author_sort | Eunji Park |
| collection | DOAJ |
| description | Muscle atrophy is characterized by a decline in muscle mass and function. Excessive glucocorticoids in the body due to aging or drug treatment can promote muscle wasting. In this study, we investigated the preventive effect of <i>Nelumbo nucifera</i> 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. |
| first_indexed | 2024-03-11T08:20:18Z |
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| language | English |
| last_indexed | 2024-03-11T08:20:18Z |
| publishDate | 2023-02-01 |
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| series | Nutrients |
| spelling | doaj.art-e1ef86cc8e194fe7b8d3240a613b7a792023-11-16T22:29:12ZengMDPI AGNutrients2072-66432023-02-0115480410.3390/nu15040804The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle AtrophyEunji Park0Hojung Choi1Cao-Sang Truong2Hee-Sook Jun3Gachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaGachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaGachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaGachon Institute of Pharmaceutical Science, College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaMuscle atrophy is characterized by a decline in muscle mass and function. Excessive glucocorticoids in the body due to aging or drug treatment can promote muscle wasting. In this study, we investigated the preventive effect of <i>Nelumbo nucifera</i> 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.https://www.mdpi.com/2072-6643/15/4/804muscle atrophynelumbo nuciferapyroptosisautophagyprotein degradation |
| spellingShingle | Eunji Park Hojung Choi Cao-Sang Truong Hee-Sook Jun The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy Nutrients muscle atrophy nelumbo nucifera pyroptosis autophagy protein degradation |
| title | The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy |
| title_full | The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy |
| title_fullStr | The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy |
| title_full_unstemmed | The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy |
| title_short | The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of <i>Nelumbo nucifera</i> Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy |
| title_sort | inhibition of autophagy and pyroptosis by an ethanol extract of i nelumbo nucifera i leaf contributes to the amelioration of dexamethasone induced muscle atrophy |
| topic | muscle atrophy nelumbo nucifera pyroptosis autophagy protein degradation |
| url | https://www.mdpi.com/2072-6643/15/4/804 |
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