A recent study reveals the potential of carnosol, a compound found in rosemary leaf extract, in inducing hypertrophy in human skeletal muscle cells (4). The research shows that carnosol mediates its effects by inhibiting E3 ubiquitin ligase MuRF1 and the proteasome, two elements involved in protein degradation in muscles. This discovery has significant implications for the treatment or prevention of skeletal muscle atrophy.
Carnosol and Muscle Hypertrophy
Muscle hypertrophy, the increase in muscle size, is vital for strength and overall health. Carnosol, a compound found in rosemary leaf extract, has been found to have a hypertrophic effect on human muscle cells. This effect is mediated through the inhibition of the E3 ubiquitin ligase MuRF1 and of the proteasome, which are key players in muscle protein degradation (4).
Role of MuRF1 and Proteasome in Muscle Atrophy
In muscles, proteins can be degraded through various pathways, one of which involves the UPS (Ubiquitin Proteasome System), the most significant pathway in muscle atrophy. Ubiquitination, essential for protein targeting to the proteasome complex, involves the action of E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin ligases. In muscles, the E3 ubiquitin ligases MAFbx and MuRF1 are major markers of muscle atrophy. Carnosol inhibits MuRF1, thereby reducing protein degradation and promoting muscle hypertrophy (1, 4).
Specificity of Carnosol-Induced Muscle Hypertrophy
Interestingly, the research found that carnosol specifically stimulates the hypertrophy of type I muscle fibers, which are slow-twitch fibers. These fibers possess slower twitch speeds but are relatively fatigue resistant. Therefore, carnosol, by promoting type I muscle fibers, could potentially make the skeletal muscle more resistant to fatigue and more enduring (2, 4).
Carnosol's Potential in Preventing Skeletal Muscle Atrophy
Several strategies have been developed to find natural molecules that could help prevent or treat skeletal muscle atrophy by stimulating protein synthesis and/or inhibiting protein degradation. Carnosol, identified as an anabolic compound in rosemary leaf extract, has shown promise in this area. It inhibits the E3 ubiquitin ligase MuRF1 and proteasome activity, thus reducing protein degradation. This opens up new possibilities for using carnosol in the treatment or prevention of skeletal muscle atrophy (3, 4).
These findings contribute to a growing body of research exploring natural compounds as potential therapeutic agents for muscle atrophy. Further studies are needed to fully understand the mechanisms by which carnosol regulates muscle protein degradation and to evaluate its potential therapeutic implications.
Conclusion
The discovery of carnosol's role in inducing hypertrophy in human skeletal muscle cells offers promising avenues for the treatment and prevention of muscle atrophy. By inhibiting protein degradation pathways, carnosol has the potential to combat muscle wasting and enhance endurance, especially in type I muscle fibers.
References
- Bodine, S.C. Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome. J. Appl. Physiol. (1985) 2020, 129, 272–282.
- Kitajima, Y.; Yoshioka, K.; Suzuki, N. The ubiquitin-proteasome system in regulation of the skeletal muscle homeostasis and atrophy: From basic science to disorders. J. Physiol. Sci. 2020, 70, 40.
- Peris-Moreno, D.; Taillandier, D.; Polge, C. MuRF1/TRIM63, Master Regulator of Muscle Mass. Int. J. Mol. Sci. 2020, 21, 6663.
- 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, 4190. https://doi.org/10.3390/nu13124190