Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation
- PDF / 14,780,070 Bytes
- 19 Pages / 595.276 x 790.866 pts Page_size
- 2 Downloads / 164 Views
Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down‑regulation of estrogen receptor α expression Xinyu Long1 · Yanfang Gao1 · Weiwei Liu1 · Xiaoling Liu1 · Toshihiko Hayashi1,2 · Kazunori Mizuno3 · Shunji Hattori3 · Takashi Ikejima1,4,5 Received: 21 April 2020 / Accepted: 20 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Skeletal muscle regeneration is a complex process, involving the proliferation, migration, and differentiation of myoblasts. Recent studies suggest that some natural flavanones stimulate myogenesis. However, the effect of plant estrogen, silibinin, on the regulation of myoblast behaviors is unclarified. In this study, we investigated the effects of silibinin on immortalized murine myoblast C2C12 in the aspects of proliferation, migration, differentiation along with underlying mechanisms. The results show that silibinin at concentrations below 50 μM enhanced the migration and differentiation of C2C12 cells, but had no effect on cell proliferation. Silibinin significantly promoted the production of ROS, which appeared to play important roles in the migration and differentiation of the myoblasts. Interestingly, among ROS, the superoxide anion and hydroxyl radical were associated with the migration, whereas hydrogen peroxide contributed to the myogenic differentiation. We used ER agonist and antagonist to explore whether estrogen receptors (ERs), which are affected by silibinin treatment in the silibinin-enhanced C2C12 migration and differentiation. Migration was independent of ERs, whereas the differentiation was associated with decreased ERα activity. In summary, silibinin treatment increases ROS levels, leading to the promotion of migration and myogenic differentiation. Negative regulation ERα of differentiation but not of migration may suggest that ERα represses hydrogen peroxide generation. The effect of silibinin on myoblast migration and differentiation suggests that silibinin may have therapeutic benefits for muscle regeneration. Keywords Silibinin · C2C12 cells · Migration · Myogenic differentiation · ROS · Estrogen receptors (ERs)
Introduction * Takashi Ikejima [email protected] 1
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, People’s Republic of China
2
Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665‑1, Nakanomachi, Hachioji, Tokyo 192‑0015, Japan
3
Nippi Research Institute of Biomatrix, Ibaraki 649‑1211, Japan
4
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development Liaoning Province, 103 Wenhua Road, Shenyang 110016, Liaoning, China
5
China‑Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning, China
Skeletal muscle is composed of bundled muscle fibers, which account for about 50–60% of fat-free body mas
Data Loading...
