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Boldo Restores Vascularization and Reduces Skeletal Muscle Inflammation in Symptomatic Mice with Dysferlinopathy
Walter Vásquez1, Felipe Troncoso2, Andrea Lira3
1Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.
Abstract:
Dysferlinopathies are progressive muscular dystrophies caused by DYSF mutations, leading to impaired membrane repair, chronic inflammation, lipid accumulation, and muscle degeneration. No approved therapies currently halt the progression of this disease. Here, we evaluated the effects of daily oral administration of pulverized Boldo (Peumus boldus) leaves, commonly used as a nutraceutical, to blAJ mice, a model of dysferlinopathy. Symptomatic bIAJ mice were treated for four weeks with Boldo and presented significantly improved grip strength and restored endothelial-dependent vasodilation. Muscle perfusion and capillary density in the gastrocnemius were both enhanced by treatment. Histological analyses revealed that Boldo prevented myofiber atrophy, reduced centrally nucleated fibers, and improved muscle tissue architecture. Lipid accumulation observed in blAJ muscles was absent in Boldo-treated mice. At the cellular level, Boldo normalized sarcolemma membrane permeability (dye uptake) and reduced mRNA levels of inflammasome components (NLRP3, ASC, and IL-1β), suggesting anti-inflammatory activity. These findings indicate that Boldo improves vascular and muscle integrity, supporting its potential as a complementary therapeutic strategy for dysferlinopathy.
Insights
Boldo (Peumus boldus) supplementation improved muscle strength and vascular function in a mouse model of dysferlinopathy. This nutraceutical demonstrated potential in preventing muscle degeneration and inflammation, offering a promising complementary therapy.
Area of Science:
- Biomedical Science
- Molecular Biology
- Pharmacology
Background:
- Dysferlinopathies are genetic muscular dystrophies resulting from DYSF gene mutations.
- These conditions cause progressive muscle degeneration due to impaired membrane repair and chronic inflammation.
- Currently, no approved therapies can halt the progression of dysferlinopathies.
Purpose of the Study:
- To investigate the therapeutic potential of Boldo (Peumus boldus) leaves in treating dysferlinopathy.
- To evaluate the effects of oral Boldo administration on muscle function, vascular integrity, and cellular pathology in a mouse model.
Main Methods:
- Daily oral administration of pulverized Boldo leaves to symptomatic bIAJ mice (a dysferlinopathy model) for four weeks.
- Assessment of grip strength, vasodilation, muscle perfusion, and capillary density.
- Histological analysis of muscle tissue, including myofiber size, central nucleation, and architecture.
- Evaluation of sarcolemma permeability and mRNA levels of inflammasome components (NLRP3, ASC, IL-1β).
Main Results:
- Boldo treatment significantly improved grip strength and restored endothelial-dependent vasodilation.
- Enhanced muscle perfusion and capillary density were observed in the gastrocnemius muscle.
- Histology showed prevention of myofiber atrophy, reduced central nucleation, and improved muscle architecture.
- Boldo administration normalized sarcolemma permeability and reduced inflammasome-related gene expression, indicating anti-inflammatory effects.
- Lipid accumulation in muscles was notably absent in Boldo-treated mice.
Conclusions:
- Oral administration of Boldo demonstrates significant therapeutic benefits in a mouse model of dysferlinopathy.
- Boldo improves both vascular and muscle integrity, suggesting its potential as a complementary treatment.
- The findings support Boldo's role in mitigating key pathological features of dysferlinopathy, including inflammation and degeneration.
