Broccoli-Derived Peptides and Leucine in Combination Ameliorate D-Galactose-Induced Sarcopenia in Mice.

<h4>Background</h4>Sarcopenia is an age-related disorder characterized by loss of muscle mass, strength, and function, driven by oxidative stress, chronic inflammation, and protein imbalance. Broccoli-derived peptides (BDP) exert anti-inflammatory and myofiber-protective effects, while leucine regulates energy metabolism and redox balance.<h4>Methods</h4>We established a D-galactose aging mouse model and treated mice with BDP alone, leucine alone, or their combination for 8 weeks. Lean mass, muscle index, grip strength, endurance, and treadmill capacity were detected, and atrophic, disorganized myofibers were observed through histology. RNA-seq was applied to screen differential signaling pathways, and qPCR was used to verify related gene expression levels.<h4>Results</h4>D-galactose caused marked deficits in lean mass, muscle index, grip strength, endurance, and treadmill capacity, accompanied by atrophic and disorganized myofibers. Single BDP or leucine partially reversed these deficits, but the combination produced the most robust improvements. RNA-seq revealed that BDP enriched actin, chemokine, and TNF pathways; leucine enriched Apelin and ECM pathways; while the combination uniquely regulated MAPK signaling. qPCR confirmed that co-administration optimally upregulated myogenic drivers (<i>Myod1</i>, <i>Myog</i>, <i>Mef2c</i>), suppressed catabolic/inflammatory mediators (<i>Mstn</i>, <i>Tnf</i>, <i>Cxcl10</i>), and restored metabolic/adhesive regulators (<i>Sirt3</i>, <i>Aplnr</i>, <i>Icam1</i>).<h4>Conclusions</h4>BDP and leucine show superior efficacy in ameliorating sarcopenia, through multimodal regulation of multiple signaling pathways, offering a promising plant-based nutritional strategy against age-related muscle decline.