Beneficial effects of β-escin on muscle regeneration in rat model of skeletal muscle injury

• Published in: Phytomedicine (Stuttgart) 2021-12, Vol.93, p.153791-153791, Article 153791
• Main Authors: Sikorska, Maria, Dutkiewicz, Małgorzata, Zegrocka – Stendel, Oliwia, Kowalewska, Magdalena, Grabowska, Iwona, Koziak, Katarzyna
• Format: Article
• Language: English
• Subjects: ALDH; macrophage; MMP, muscle; NF-κB; β-escin
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2021.153791

•β-escin facilitates muscle regeneration.•β-escin rescues muscles from atrophy, reduces inflammation and decreases fibrosis.•β-escin reduces macrophage infiltration and promotes their M2 polarization.•β-escin alters transcription of muscle regeneration-related genes.•β-escin reduces secretion of MMP-9 and increases ALDH activity. Recent advancements in understanding β-escin action provide basis for new therapeutic claims for the drug. β-escin-evoked attenuation of NF-κB-dependent signaling, increase in MMP-14 and decrease in COUP-TFII content and a rise in cholesterol biosynthesis could be beneficial in alleviating muscle-damaging processes. The aim of this study was to investigate the effect of β-escin on skeletal muscle regeneration. Rat model of cardiotoxin-induced injury of fast-twich extensor digitorum longus (EDL) and slow-twich soleus (SOL) muscles and C2C12 myoblast cells were used in the study. We evaluated muscles obtained on day 3 and 14 post-injury by histological analyses of muscle fibers, connective tissue, and mononuclear infiltrate, by immunolocalization of macrophages and by qPCR to quantify the expression of muscle regeneration-related genes. Mechanism of drug action was investigated in vitro by assessing cell viability, NF-κB activation, MMP-2 and MMP-9 secretion, and ALDH activity. In rat model, β-escin rescues regenerating muscles from atrophy. The drug reduces inflammatory infiltration, increases the number of muscle fibers and decreases fibrosis. β-escin reduces macrophage infiltration into injured muscles and promotes their M2 polarization. It also alters transcription of muscle regeneration-related genes: Myf5, Myh2, Myh3, Myh8, Myod1, Pax3 and Pax7, and Pcna. In C2C12 myoblasts in vitro, β-escin inhibits TNF-α-induced activation of NF-κB, reduces secretion of MMP-9 and increases ALDH activity. The data reveal beneficial role of β-escin in muscle regeneration, particularly in poorly regenerating slow-twitch muscles. The findings provide rationale for further studies on β-escin repositioning into conditions associated with muscle damage such as strenuous exercise, drug-induced myotoxicity or age-related disuse atrophy. [Display omitted]