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Protective Effects of the Phytocannabinoid Cannabidiol on Disuse-Induced Muscle Atrophy through Modulation of
Hiromasa Kato1, Iori Uratsuji1, Yui Nakadai1
1Department of Pharmacokinetics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Abstract:
Muscle atrophy induced by prolonged inactivity (disuse), including denervation-induced atrophy, is accompanied by oxidative stress, inflammation, and dysregulated protein turnover, yet no effective pharmacological therapy is currently available. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has been reported to exhibit anti-inflammatory and antioxidant properties; however, its potential involvement in disuse-related muscle atrophy has not been fully characterized. In this study, to evaluate the potential effects of CBD on disuse-related muscle atrophy, we employed both in vivo and in vitro models. A mouse model of sciatic nerve resection-induced muscle atrophy was used for the in vivo experiments, while C2C12 myotubes were utilized for the in vitro analyses. In the denervated mouse model, CBD attenuated the decrease in muscle mass in the tibialis anterior and gastrocnemius muscles, as well as the decline in treadmill running performance. CBD also reduced oxidative stress and suppressed the denervation-induced upregulation of Atrogin-1 and muscle RING-finger 1 (MuRF1) proteins, as well as tumor necrosis factor-α (TNF-α) mRNA. Furthermore, CBD partially restored the decreased mitochondrial markers observed following denervation. In vitro, CBD similarly suppressed MuRF1 and Atrogin-1 protein levels and TNF-α mRNA expression in C2C12 myotubes. These findings suggest that CBD is associated with protective effects against disuse-related muscle atrophy, accompanied by reductions in oxidative stress markers, alterations in proteolytic pathways, and changes in mitochondrial-related markers. This study highlights a previously underexplored biological effect of a natural phytocannabinoid and supports further investigation of CBD as a potential supportive strategy for disuse-related muscle wasting.
Insights
Cannabidiol (CBD) may protect against muscle atrophy caused by inactivity. This study found CBD reduced muscle mass loss, oxidative stress, and inflammation in denervated muscle models, suggesting its potential for treating muscle wasting.
Area of Science:
- Biochemistry
- Pharmacology
- Muscle Physiology
Background:
- Muscle atrophy from disuse, including denervation, involves oxidative stress, inflammation, and protein turnover issues.
- Currently, no effective pharmacological treatments exist for disuse-related muscle atrophy.
- Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has demonstrated anti-inflammatory and antioxidant effects.
Purpose of the Study:
- To investigate the potential of Cannabidiol (CBD) in mitigating muscle atrophy induced by disuse.
- To characterize the effects of CBD on molecular pathways involved in muscle wasting.
Main Methods:
- In vivo: Mouse model with sciatic nerve resection to induce muscle atrophy.
- In vitro: C2C12 myotubes were used to analyze cellular responses.
- Assessed muscle mass, running performance, oxidative stress markers, key atrophy-related proteins (Atrogin-1, MuRF1), TNF-α mRNA, and mitochondrial markers.
Main Results:
- CBD treatment attenuated muscle mass reduction and improved running performance in denervated mice.
- CBD decreased oxidative stress, suppressed Atrogin-1 and MuRF1 upregulation, and reduced TNF-α mRNA.
- CBD partially restored mitochondrial markers in denervated muscles and in vitro.
Conclusions:
- Cannabidiol (CBD) exhibits protective effects against disuse-induced muscle atrophy.
- These effects are associated with reduced oxidative stress, modulation of protein degradation pathways, and improved mitochondrial function.
- CBD represents a potential supportive therapeutic strategy for muscle wasting conditions.
