Eun-Chae Cho, PhD candidate in: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Sarcopenia, an age-related decline in muscle mass and strength with unclear causes and diagnostic criteria, contributes to frailty and functional impairment in diabetes. The effects of Melilotus albus, a coumarin family plant known for anti-inflammatory properties and reducing post-operative symptoms, on muscle formation and wasting are not yet determined. The aim of this study was to explore the impact of Melilotus albus extract (MAE) on muscle cell development in myoblastic C2C12 cells and a type 2 diabetes mouse model.
Methods: For the cell differentiation study, C2C12 cells at 70% confluence were shifted to a differentiation medium with or without MAE for a period of 7 days. Additionally, this study involved the use of seven-week-old db/db mice, which start showing signs of diabetes (hyperglycemia). These mice were grouped into three categories: 1) non-diabetic db/m control mice, 2) diabetic db/db mice, and 3) diabetic db/db mice receiving an oral dose of 20 mg/kg of MAE daily for 8 weeks.
Results: Results showed that differentiated C2C12 myotubes treated with non-toxic concentrations of MAE (20 µg/ml) exhibited an increase in both the number and diameter of myotubes. This was linked to enhanced expression of myogenin and myogenic differentiation factor (MyoD), and reduced expression of Forkhead box protein O3 (FOXO3a) and muscle RING finger-1 (MuRF1). These findings indicate that MAE boosts the production of proteins crucial for muscle development and inhibits muscle wasting by regulating muscle-specific ubiquitin ligases and transcription factors in C2C12 myotubes. Oral administration of MAE in db/db mice led to an increase in myogenin and MyoD levels, effectively slowing down the muscle atrophy associated with diabetes. Furthermore, MAE treatment resulted in decreased levels of FOXO3a and MuRF1 in these mice.
Conclusions: Overall, this study demonstrates that MAE extract can promote differentiation of C2C12 myoblasts into myotubes and modulate the expression of genes involved in muscle development and degradation in both C2C12 myotubes and mouse skeletal muscle.
Funding Sources: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Science and ICT) (NRF-2022R1F1A1063827).