A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells
A good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts fr...
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MDPI AG
2021-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/12/4190 |
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| author | Sylvie Morel Gérald Hugon Manon Vitou Marie Védère Françoise Fons Sylvie Rapior Nathalie Saint Gilles Carnac |
| author_facet | Sylvie Morel Gérald Hugon Manon Vitou Marie Védère Françoise Fons Sylvie Rapior Nathalie Saint Gilles Carnac |
| author_sort | Sylvie Morel |
| collection | DOAJ |
| description | A good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophy-promoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1. |
| first_indexed | 2024-03-10T03:25:26Z |
| format | Article |
| id | doaj.art-790d15dad208460084e82cc88a552399 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T03:25:26Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-790d15dad208460084e82cc88a5523992023-11-23T09:54:14ZengMDPI AGNutrients2072-66432021-11-011312419010.3390/nu13124190A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle CellsSylvie Morel0Gérald Hugon1Manon Vitou2Marie Védère3Françoise Fons4Sylvie Rapior5Nathalie Saint6Gilles Carnac7Laboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, CEFE, Univ Montpellier, CNRS, EPHE, IRD, 34090 Montpellier, FrancePhyMedExp, Univ Montpellier, CNRS, INSERM, 34090 Montpellier, FranceLaboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, CEFE, Univ Montpellier, CNRS, EPHE, IRD, 34090 Montpellier, FrancePhyMedExp, Univ Montpellier, CNRS, INSERM, 34090 Montpellier, FranceLaboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, CEFE, Univ Montpellier, CNRS, EPHE, IRD, 34090 Montpellier, FranceLaboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, CEFE, Univ Montpellier, CNRS, EPHE, IRD, 34090 Montpellier, FrancePhyMedExp, Univ Montpellier, CNRS, INSERM, 34090 Montpellier, FrancePhyMedExp, Univ Montpellier, CNRS, INSERM, 34090 Montpellier, FranceA good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophy-promoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1.https://www.mdpi.com/2072-6643/13/12/4190<i>Salvia rosmarinus</i>stem cellsditerpeneproteasomemuscle mass |
| spellingShingle | Sylvie Morel Gérald Hugon Manon Vitou Marie Védère Françoise Fons Sylvie Rapior Nathalie Saint Gilles Carnac A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells Nutrients <i>Salvia rosmarinus</i> stem cells diterpene proteasome muscle mass |
| title | A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells |
| title_full | A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells |
| title_fullStr | A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells |
| title_full_unstemmed | A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells |
| title_short | A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells |
| title_sort | bioassay guided fractionation of rosemary leaf extract identifies carnosol as a major hypertrophy inducer in human skeletal muscle cells |
| topic | <i>Salvia rosmarinus</i> stem cells diterpene proteasome muscle mass |
| url | https://www.mdpi.com/2072-6643/13/12/4190 |
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