Abstract: OBJECTIVE: To explore mechanisms by which acteoside(ACT) ameliorates sarcopenia,and to suggest a scientific basis for treatment of sarcopenia with natural products. METHODS: Fifty 6-week-old SPF male C57 BL/6 mice were randomly divided into five groups:a negative control group(normal saline),a model group(5 mg/kg dexamethasone via intraperitoneal injection), a positive control group(5 mg/kg dexamethasone plus 0.37 mg/kg perindopril erbumine),a dexamethasone plus 50 mg/kg ACT group,and a dexamethasone plus100 mg/kg ACT group. All mice were administered intragastrically once daily for 4 consecutive weeks. Before sacrifice,fasting blood glucose concentrations were measured using a blood glucose meter. Serum levels of tumor necrosis factor-α(TNF-α) were determined by ELISA. After sacrifice, gastrocnemius muscle tissues were harvested, and glycogen deposition in skeletal muscle was evaluated by Periodic Acid-Schiff(PAS) staining.Protein expression levels of matrix metalloproteinase-9(MMP-9) in skeletal muscle were detected by immunohistochemistry. RESULTS: Compared with the negative control mice, dexamethasone-induced sarcopenia in mice exhibited impaired glucose tolerance(P<0.01),and serum levels of the pro-inflammatory factor TNF-αwere significantly elevated(P<0.01). Compared with the 50 mg/kg ACT intervention group,glucose tolerance was partially restored in the 100 mg/kg ACT intervention group. Compared with the model group, TNF-αconcentrations were decreased in both ACT intervention groups(P<0.01). Compared with the negative control mice,model mice showed markedly reduced glycogen deposition between muscle fibers,with sparse distribution and weakened staining intensity of magenta granules. Additionally, MMP-9 protein expression was abnormally increased and widely distributed in the intermuscular fiber spaces. In contrast, the ACT intervention groups exhibited increased density of glycogen granule deposition and significantly reduced intensity of MMP-9 positive signals. Among them, the PAS staining intensity and MMP-9 distribution pattern in the 100 mg/kg ACT intervention group were restored to near-normal levels. CONCLUSION: ACT regulated blood glucose concentration in vivo in a dose-dependent manner. Mechanistically, it ameliorated pathological progression of sarcopenia by inhibiting TNF-α-and MMP-9-mediated inflammatory responses and excessive degradation of the extracellular matrix. These findings provide a pharmacological basis for development of natural product-based drugs in prevention and treatment of sarcopenia.

Key words: acteoside, sarcopenia, dexamethasone, glycogen metabolism, muscle fibers