Rutin–Whey Protein Nanoparticles Inhibit D-Galactose-Induced Skeletal Muscle Dysfunction by Modulating Gut Microbiota and Metabolic Pathways

Background: Rutin (R) is a bioactive compound with antioxidant and anti-inflammatory properties, but its low bioavailability limits its application. To address this problem, R was encapsulated with whey protein (W) as nanoparticles, and the potential effect and mechanism of rutin–whey protein nanoparticles (RW) on skeletal muscle dysfunction was investigated in D-galactose induced mice.Methods: R was encapsulated with W to form RW, and its characteristics like particle size, encapsulation efficiency, and bioaccessibility were evaluated. In the in vivo study, male C57BL/6J mice were treated with R, W or RW, respectively. The muscle function, hepatic antioxidant capacity, serum inflammatory levels, gut microbiota, and metabolomic profiles of mice were evaluated.Results: RW showed a uniform particle size, with an encapsulation efficiency of 68.7%. In the RW, the bioaccessibility of rutin was approximately 3.3 times that of free rutin. This in vivo study indicated that in comparison with D-galactose induced mice (model group), R, W and RW treatments could enhance hepatic antioxidative capacity and regulate inflammation levels, while W and RW could also increase muscle strength. Among these, RW treatment significantly elevated the hepatic GSH-PX activity and decreased the serum MSTN, TNF-α, and IL-6 levels, which were all markedly better than those of the individual effect of R or W. Such effects of R, W, and RW may be achieved through the modulation of gut microbiota that produced short-chain fatty acids or involved in anti-inflammatory function and the regulation of metabolic profiles associated with amino acid metabolism, aminoacyl-tRNA biosynthesis, etc.Conclusions: RW was found to enhance the bioaccessibility of rutin, and exhibited positive effects on skeletal muscle dysfunction via the modulation of gut microbiota and metabolic pathways. The results of this study may provide new scientific strategy for the utilization of rutin to achieve its health benefits.