Andrea Lira

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.

Dysferlinopathies are progressive muscular dystrophies caused by mutations in the DYSF gene, leading to defective membrane repair, chronic inflammation, lipid accu-mulation, and muscle degeneration. No approved therapies currently halt disease progression. This study evaluated the effects of daily oral administration of pulverized Boldo (Peumus boldus) leaves, a nutraceutical with reported bioactive properties, in symptomatic blAJ mice, a model of dysferlinopathy. Mice received Boldo for four weeks, and muscle function, vascular performance, histology, and molecular markers were assessed. Boldo treated mice exhibited significantly improved grip strength and restored endothelium dependent vasodilation. Gastrocnemius muscle perfusion and capillary density increased after treatment. Histological analysis revealed prevention of myofiber atrophy, a reduction in centrally nucleated fibers, and improved tissue architecture. Lipid accumulation observed in untreated blAJ mice was absent with Boldo. At the cellular level, Boldo normalized sarcolemmal membrane permeability and decreased mRNA levels of inflammasome components (NLRP3, ASC, IL-1β), suggesting anti-inflammatory activity. These results indicate that Boldo improves vascular and muscle integrity in dysferlinopathy and support its potential as a com-plementary therapeutic strategy.