Mechanism of Qigu capsule as a treatment for sarcopenia based on network pharmacology and experimental validation.

Abstract

Objective: To explore the potential molecular mechanism of Qigu capsule (，QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.

Methods: The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases. Then the herbs-compounds-targets network, and protein-protein interaction (PPI) network was constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by R software. Next, we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.

Results: A total of 57 common targets of QGC and sarcopenia were obtained. Based on the enrichment analysis of GO and KEGG, we took the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia. Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy. In the model group, the expression of muscle ring finger-1 and Atrogin-1 were increased, while myosin heavy chain was decreased, QGC treatment reversed these changes. Moreover, compared with the model group, the expressions of p-PI3K, p-Akt, p-mammalian target of rapamycin and p-Forkhead box O3 in the QGC group were all upregulated.

Conclusion: QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.