Network pharmacology analysis and in vitro verification of the anti-sarcopenia effects of formononetin

Sarcopenia (SP) associated with functional impairment is highly prevalent; however, therapeutic strategies addressing this condition remain limited. Inflammation and oxidative stress are the key contributors. Suitably, formononetin (FMN) offers diverse benefits, including antioxidant, anti-apoptotic, and anti-inflammatory properties. Therefore, this study used network pharmacology to identify 81 potential target genes for FMN to alleviate SP. Serine/threonine-protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), and sirtuin 1 (SIRT1) as the core targets. Kyoto Encyclopedia of Genes and Genome analysis indicated that FMN primarily affects SP via the interleukin (IL)-17, PI3K-Akt and FoxO signalling pathways. Cell studies revealed that FMN reduces IL-6 release and boosts superoxide dismutase activity, thereby enhancing C2C12 skeletal muscle cell vitality. FMN intervention also enhanced AKT1 and SIRT1 gene and protein expression, decreased muscle-specific RING finger protein-1 gene expression, and increased EGFR protein expression. This suggests its anti-inflammatory and antioxidant effects in dexamethasone-treated C2C12 cells, potentially preventing muscle atrophy by inhibiting protein breakdown. These findings highlight the promising multi-target role and molecular mechanism of FMN in the treatment of SP and suggest future clinical applications.