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Nutrients
Volume 13
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10.3390/nu13124190
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Article

A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells

by
Sylvie Morel
1,
Gérald Hugon
2,
Manon Vitou
1,
Marie Védère
2,
Françoise Fons
1,
Sylvie Rapior
1,
Nathalie Saint
2,† and
Gilles Carnac
2,*,†
1
Laboratoire de Botanique, Phytochimie et Mycologie, Faculté de Pharmacie, CEFE, Univ Montpellier, CNRS, EPHE, IRD, 34090 Montpellier, France
2
PhyMedExp, Univ Montpellier, CNRS, INSERM, 34090 Montpellier, France
*
Author to whom correspondence should be addressed.
†
Both authors equally contributed to this work.
Nutrients 2021, 13(12), 4190; https://doi.org/10.3390/nu13124190
Submission received: 29 September 2021 / Revised: 17 November 2021 / Accepted: 18 November 2021 / Published: 23 November 2021
(This article belongs to the Special Issue Nutrition and Regulation of Muscle Protein Synthesis)
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Abstract

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.
Keywords: Salvia rosmarinus; stem cells; diterpene; proteasome; muscle mass Salvia rosmarinus; stem cells; diterpene; proteasome; muscle mass
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MDPI and ACS Style

Morel, S.; Hugon, G.; Vitou, M.; Védère, M.; Fons, F.; Rapior, S.; Saint, N.; Carnac, G. A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells. Nutrients 2021, 13, 4190. https://doi.org/10.3390/nu13124190

AMA Style

Morel S, Hugon G, Vitou M, Védère M, Fons F, Rapior S, Saint N, Carnac G. A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells. Nutrients. 2021; 13(12):4190. https://doi.org/10.3390/nu13124190

Chicago/Turabian Style

Morel, Sylvie, Gérald Hugon, Manon Vitou, Marie Védère, Françoise Fons, Sylvie Rapior, Nathalie Saint, and Gilles Carnac. 2021. "A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells" Nutrients 13, no. 12: 4190. https://doi.org/10.3390/nu13124190

APA Style

Morel, S., Hugon, G., Vitou, M., Védère, M., Fons, F., Rapior, S., Saint, N., & Carnac, G. (2021). A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells. Nutrients, 13(12), 4190. https://doi.org/10.3390/nu13124190

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