Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy
Abstract To investigate the pharmacological mechanisms by extract of Polyporus umbellatus (PU) protects against dexamethasone (DEX)-induced muscle atrophy, focusing on its direct effects on muscle cell signaling, mitochondrial function, oxidative stress, and its indirect influence via gut microbiota...
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SpringerOpen
2025-07-01
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| Series: | Applied Biological Chemistry |
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| Online Access: | https://doi.org/10.1186/s13765-025-01014-9 |
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| author | Nguyen Bao Ngoc Subeen Kim Hye-Young Youn Huitae Min Tam Thi Le Mauliasari Intan Rizki Dae Won Kim Kwang Hyeon Cha Young Tae Park Sang Hoon Jung Myungsuk Kim |
| author_facet | Nguyen Bao Ngoc Subeen Kim Hye-Young Youn Huitae Min Tam Thi Le Mauliasari Intan Rizki Dae Won Kim Kwang Hyeon Cha Young Tae Park Sang Hoon Jung Myungsuk Kim |
| author_sort | Nguyen Bao Ngoc |
| collection | DOAJ |
| description | Abstract To investigate the pharmacological mechanisms by extract of Polyporus umbellatus (PU) protects against dexamethasone (DEX)-induced muscle atrophy, focusing on its direct effects on muscle cell signaling, mitochondrial function, oxidative stress, and its indirect influence via gut microbiota modulation. In vitro, DEX-treated C2C12 myotubes were used to assess PU’s effects on cell viability, myotube morphology, myogenic/atrophy gene expression, Akt/mTOR/FoxO3a signaling pathways, mitochondrial function, and oxidative stress. In vivo, a DEX-induced muscle atrophy mouse model was employed to evaluate the efficacy of orally administered PU and L. gasseri (ATCC 19992) alone on muscle mass, strength, exercise performance, and gene expression. Gut microbiota composition was analyzed via 16 S rRNA sequencing, with predicted microbial enzyme functions and correlations to muscle parameters examined. In vitro, PU significantly attenuated DEX-induced C2C12 myotube atrophy, activated Akt/mTOR signaling, inhibited FoxO3a signaling, mitigated oxidative stress, and enhanced mitochondrial function. In vivo, PU dose-dependently improved grip strength, muscle mass, and exercise performance in DEX-treated mice, concurrently upregulating myogenic and mitochondrial biogenesis genes. PU treatment significantly modulated gut microbial diversity and composition, notably increasing L. gasseri abundance. Oral administration L. gasseri recapitulated PU’s protective effects on muscle phenotype, gene expression, and gut microbiota modulation. L. gasseri levels and predicted microbial D-lactate dehydrogenase activity correlated positively with muscle health. However, bioactivity-guided fractionation of PU did not identify a single predominant active compound. In conclusion, PU protects against glucocorticoid-induced muscle atrophy through a dual mechanism involving direct muscle-protective actions and beneficial modulation of the gut microbiota, partly mediated by enrichment and direct effects of L. gasseri. Graphical Abstract |
| format | Article |
| id | doaj-art-7dfc707feef64e1a9b34b36bb6709897 |
| institution | Kabale University |
| issn | 2468-0842 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Applied Biological Chemistry |
| spelling | doaj-art-7dfc707feef64e1a9b34b36bb67098972025-08-20T03:43:10ZengSpringerOpenApplied Biological Chemistry2468-08422025-07-0168112210.1186/s13765-025-01014-9Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophyNguyen Bao Ngoc0Subeen Kim1Hye-Young Youn2Huitae Min3Tam Thi Le4Mauliasari Intan Rizki5Dae Won Kim6Kwang Hyeon Cha7Young Tae Park8Sang Hoon Jung9Myungsuk Kim10Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Graduate School of Engineering Biology, Korea Advanced Institute of Science & Technology (KAIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST)College of Dentistry, Gangneung Wonju National UniversityCenter for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Center for Natural Product Efficacy Optimization, Korea Institute of Science and Technology (KIST)Abstract To investigate the pharmacological mechanisms by extract of Polyporus umbellatus (PU) protects against dexamethasone (DEX)-induced muscle atrophy, focusing on its direct effects on muscle cell signaling, mitochondrial function, oxidative stress, and its indirect influence via gut microbiota modulation. In vitro, DEX-treated C2C12 myotubes were used to assess PU’s effects on cell viability, myotube morphology, myogenic/atrophy gene expression, Akt/mTOR/FoxO3a signaling pathways, mitochondrial function, and oxidative stress. In vivo, a DEX-induced muscle atrophy mouse model was employed to evaluate the efficacy of orally administered PU and L. gasseri (ATCC 19992) alone on muscle mass, strength, exercise performance, and gene expression. Gut microbiota composition was analyzed via 16 S rRNA sequencing, with predicted microbial enzyme functions and correlations to muscle parameters examined. In vitro, PU significantly attenuated DEX-induced C2C12 myotube atrophy, activated Akt/mTOR signaling, inhibited FoxO3a signaling, mitigated oxidative stress, and enhanced mitochondrial function. In vivo, PU dose-dependently improved grip strength, muscle mass, and exercise performance in DEX-treated mice, concurrently upregulating myogenic and mitochondrial biogenesis genes. PU treatment significantly modulated gut microbial diversity and composition, notably increasing L. gasseri abundance. Oral administration L. gasseri recapitulated PU’s protective effects on muscle phenotype, gene expression, and gut microbiota modulation. L. gasseri levels and predicted microbial D-lactate dehydrogenase activity correlated positively with muscle health. However, bioactivity-guided fractionation of PU did not identify a single predominant active compound. In conclusion, PU protects against glucocorticoid-induced muscle atrophy through a dual mechanism involving direct muscle-protective actions and beneficial modulation of the gut microbiota, partly mediated by enrichment and direct effects of L. gasseri. Graphical Abstracthttps://doi.org/10.1186/s13765-025-01014-9Polyporus umbellatusMuscle atrophyDexamethasoneMitochondrial biogenesisGut microbiotaLactobacillus gasseri |
| spellingShingle | Nguyen Bao Ngoc Subeen Kim Hye-Young Youn Huitae Min Tam Thi Le Mauliasari Intan Rizki Dae Won Kim Kwang Hyeon Cha Young Tae Park Sang Hoon Jung Myungsuk Kim Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy Applied Biological Chemistry Polyporus umbellatus Muscle atrophy Dexamethasone Mitochondrial biogenesis Gut microbiota Lactobacillus gasseri |
| title | Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy |
| title_full | Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy |
| title_fullStr | Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy |
| title_full_unstemmed | Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy |
| title_short | Modulation of muscle anabolism and gut microbiota by Polyporus umbellatus extract attenuates dexamethasone-induced muscle atrophy |
| title_sort | modulation of muscle anabolism and gut microbiota by polyporus umbellatus extract attenuates dexamethasone induced muscle atrophy |
| topic | Polyporus umbellatus Muscle atrophy Dexamethasone Mitochondrial biogenesis Gut microbiota Lactobacillus gasseri |
| url | https://doi.org/10.1186/s13765-025-01014-9 |
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