iProXProteomicsDachuan WangMus Musculushttp://www.iprox.org/page/project.html?id=IPX0018422000wangdachuan@medmail.com.cnThe Second Qilu Hospital of Shandong UniversityiProXfalseHippophae rhamnoides-Derived Exosome-like Nanovesicles Alleviate Dexamethasone-Induced Sarcopenia by Remodeling Skeletal Muscle Lipid MetabolismSkeletal muscle atrophy driven by glucocorticoid excess is a clinically relevant contributor to sarcopenia, yet safe and biologically integrated interventions remain limited. Here we report that extracellular exosome-like nanovesicles derived from Hippophae rhamnoides fruits (HR-ELNs) protect against dexamethasone-induced muscle wasting. HR-ELNs isolated by sucrose density gradient ultracentrifugation exhibited nanoscale vesicular morphology and carried a metabolite-rich cargo. In C2C12 cells, HR-ELNs were rapidly internalized and localized predominantly in the cytoplasm, where they counteracted dexamethasone-induced upregulation of Atrogin-1 and MuRF1, downregulation of MyoG, and reduction of MyHC-positive myotube area. In a dexamethasone-induced sarcopenia mouse model, intramuscular HR-ELN administration improved grip strength and treadmill endurance while attenuating the increase in body fat content. Multi-omics profiling of skeletal muscle revealed coordinated transcriptomic and proteomic remodeling after HR-ELN treatment, with convergent enrichment of lipid metabolism, fatty acid degradation, AMPK signaling and PPAR-related pathways. Histological analyses further supported reduced lipid deposition and altered PPAR immunoreactivity in gastrocnemius muscle. Together, these findings identify HR-ELNs as bioactive plant-derived nanovesicles that couple anti-atrophic and metabolic effects, and suggest a natural nanotherapeutic strategy for glucocorticoid-associated skeletal muscle dysfunction.Thu Jul 16 00:00:00 GMT+01:00 2026PXD08122710090