Puerarin Ameliorates Sarcopenia in Aged Mice via Modulation of Inflammation and Oxidative Stress: Insights from Proteomics and Transcriptomics

Abstract

Sarcopenia, a chronic degenerative condition associated with aging, is characterized by a significant decline in muscle mass and strength. Puerarin, a major active isoflavone extracted from Pueraria lobata, exhibits potent anti-inflammatory and antioxidant properties. However, its therapeutic effects on sarcopenia remain unclear. Thus, the purpose of this study was to evaluate the therapeutic effects and underlying molecular mechanisms of puerarin in ameliorating sarcopenia in naturally aged mice. Twenty-month-old male C57BL/6 J aged mice were randomly divided into two groups based on body weight: the puerarin group (puerarin dissolved in double-distilled water, 150 mg/kg/day) and the control group (equal volume of double-distilled water). After an 8-week intervention, changes in muscle mass and function between the two groups were compared. Techniques such as HE staining, immunofluorescence staining, ELISA, transmission electron microscopy, Western blot, and qRT-PCR were employed to evaluate the positive effects of puerarin on sarcopenia in naturally aged mice. Furthermore, serum proteomics and muscle transcriptomics were used to analyze the molecular mechanisms underlying the anti-muscle atrophy effects of puerarin. The results demonstrated that puerarin significantly improved body composition, enhanced muscle mass and function, and exerted its effects by modulating inflammatory cytokines, reducing oxidative stress, and inhibiting the expression of apoptosis proteins in skeletal muscle. Additionally, integrated proteomics and transcriptomics analyses suggested that the anti-muscle atrophy mechanisms of puerarin might be related to the TNF-α/NF-κB signaling pathway. These findings highlight puerarin's potential as a therapeutic agent for sarcopenia, providing a foundation for further research and clinical application.