(P26-053-25) Herniarin, 7-Methoxycoumarin, Alleviates Muscle Atrophy in Dexamethasone-Induced C2C12 Cells by Modulating sirtuin1 and PGC1α

Objectives: Skeletal muscle atrophy, characterized by a reduction in muscle mass and muscle strength, is an important issue in the state of sarcopenia. Herniarin, one of the naturally-occurring coumarin derivatives, exhibits a variety of beneficial properties such as anticancer, anti-inflammatory, and antidiabetic. However, the effects of herniarin on skeletal muscle atrophy are not yet known. This study aimed to investigate the protective effects of herniarin against dexamethasone-induced muscle atrophy in C2C12 myotubes.

Methods: C2C12 myoblasts were differentiated into myotubes by culture with a media containing 2% horse serum for 6 days. Subsequently, the differentiated myotubes were treated with 0.2 mM dexamethasone and 1-20 μM herniarin for 24 h.

Results: Herniarin significantly enhanced the viability of myotubes treated with dexamethasone, demonstrating its protective effects against muscle atrophy. Herniarin reduced the induction of forkhead box class O3a (Foxo3a), a key transcription factor of muscle atrophy-related genes. In addition, this compound suppressed the expression of sirtuin1 (Sirt1) and peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC1α), which are regulators of Foxo3a and control cellular stress responses. Furthermore, herniarin enhanced the activation of mTOR involved in regulating protein synthesis.

Conclusions: Herniarin protects against dexamethasone-induced skeletal muscle atrophy by improving skeletal muscle cell viability, inhibiting muscle atrophy-related gene expression, and modulating key signaling pathways including Sirt1, PGC1α, and mTOR.

Funding Sources: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea, RS-2021-NR060133 and 2022R1A2B5B01001861.