(P22-013-25) Therapeutic Potential of Melilotus albus Extract in Modulating Muscle-Specific Gene Expression and Mitigating Diabetes-Associated Muscle Wasting

Objectives: Sarcopenia, an age-related decline in muscle mass and strength, exacerbates frailty and functional impairment in diabetes by dysregulating muscle-specific genes. Melilotus albus, a plant with anti-inflammatory properties, may offer therapeutic benefits. This study investigated the effects of Melilotus albus extract (MAE) on skeletal muscle differentiation in C2C12 myoblasts and diabetes-induced changes in muscle-specific gene expression in db/db mice.

Methods: C2C12 cells were cultured in differentiation medium with or without 20 µg/ml MAE for 7 days. Seven-week-old db/db mice, a type 2 diabetes model, were divided into three groups: 1) non-diabetic db/m controls, 2) diabetic db/db mice, and 3) db/db mice treated with 20 mg/kg MAE daily for 12 weeks.

Results: MAE enhanced myotube formation in C2C12 cells, upregulated myogenic differentiation 1 (MyoD1) and Myogenin, and downregulated forkhead box O-3a (FoxO3a) and muscle ring finger 1 (MuRF1), suggesting enhanced differentiation and reduced degradation. In gastrocnemius muscle, db/db mice showed reduced MyoD1, Myogenin, MuRF1, and FoxO3a expression compared to db/m controls. MAE partially restored these levels, with a significant increase in Atrogin-1. In rectus femoris, db/db mice exhibited elevated MyoD1, Myogenin, and FoxO3a. MAE reduced MyoD1 significantly, while Myogenin and FoxO3a changes were not significant. Atrogin-1 levels were significantly lower with MAE, indicating differential regulation.

Conclusions: MAE promotes myoblast differentiation and mitigates diabetes-induced muscle dysfunction by modulating muscle-specific genes, showing potential as a therapy for diabetes-associated muscle wasting.

Funding Sources: This work was supported by the National Research Foundation of Korea (NRF) (NRF-2022R1F1A1063827).