Jianpi Qiangji Granule ameliorates aging-associated sarcopenia via AMPK/PGC-1α axis in SAMP8 mice

Sarcopenia is an age-related syndrome characterized primarily by the progressive decline of muscle mass and function. It is frequently associated with adverse outcomes such as falls, fractures, and hospitalization, often leading to substantial economic burdens and severe health hazards. At present, effective pharmacological treatments for sarcopenia remain unavailable. Jianpi Qiangji Granule (JQG), a traditional Chinese medicine formula, have demonstrated significant therapeutic effects in both clinical and preclinical studies. However, its mechanism of action remains unclear.

In vivo assessment, sarcopenic mouse models were established to evaluate the effects of JQG on body weight, muscle mass, and behavioral parameters. Histopathological examination of muscle tissues was performed, including analysis of muscle fiber cross-sectional area (CSA) distribution and quantification of myofiber type-specific markers. The expression of atrophy-related proteins was measured by Western blotting. Aging-related phenotypes were scored, and senescence-associated biomarkers in muscle tissues were assessed. Transcriptomic analysis: RNA sequencing was employed to predict potential pathways through which JQG ameliorates sarcopenia. In vitro experiments utilizing JQG-containing serum and pathway-specific inhibitors were conducted to further verify the therapeutic efficacy of JQG against sarcopenia and elucidate its underlying mechanisms.

Treatment with JQG significantly increased lean body mass and exercise capacity while reducing fat mass (p < 0.05). It ameliorated histopathological alterations in muscle tissue, increased the CSA of the tibialis anterior and gastrocnemius muscle (p < 0.001), and shifted the distribution of fiber sizes toward larger diameters. JQG also attenuated the senescence score (p < 0.01), downregulated the expression of senescence-associated secretory phenotype (SASP) factors (p < 0.05), and reversed aging-related fiber type switching. Both in vivo and in vitro, JQG reduced the expression of atrophy-associated proteins and genes (Trim63, Fbxo32) (p < 0.05), thereby ameliorating muscle and myocyte atrophy. Transcriptomic analysis coupled with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment suggested that anti-atrophic effects of JQG may involve activation of AMP-activated protein kinase (AMPK) and its downstream signaling. Western blot analysis confirmed that JQG significantly activated the AMPK/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) axis. This effect was abrogated by pharmacological AMPK inhibition (Dorsomorphin) in vitro, validating AMPK/PGC-1α as the core mechanistic target.

Our results demonstrate that JQG ameliorates age-related sarcopenia by enhancing muscle mass and function, reversing pathological fiber-type transition, and attenuating muscle senescence. Critically, the AMPK/PGC-1α axis plays an essential role in mediating these therapeutic effects. Collectively, these findings suggest that JQG represents a promising candidate for the prevention and treatment of sarcopenia in aging models.