Boldo Restores Vascularization and Reduces Inflammation of Skeletal Muscle in Symptomatic Mice with 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.