Abstract

Skeletal muscle is the most abundant tissue and constitutes about 40% of total body mass. Herein, we report that crude water extract (CWE) of G. uralensis enhanced myoblast proliferation and differentiation. Pretreatment of mice with the CWE of G. uralensis prior to cardiotoxin-induced muscle injury was found to enhance muscle regeneration by inducing myogenic gene expression and downregulating myostatin expression. Furthermore, this extract reduced nitrotyrosine protein levels and atrophy-related gene expression. Of the five different fractions of the CWE of G. uralensis obtained, the ethyl acetate (EtOAc) fraction more significantly enhanced myoblast proliferation and differentiation than the other fractions. Ten bioactive compounds were isolated from the EtOAc fraction and characterized by GC-MS and NMR. Of these compounds (4-hydroxybenzoic acid, liquiritigenin, (R)-(-)-vestitol, isoliquiritigenin, medicarpin, tetrahydroxymethoxychalcone, licochalcone B, liquiritin, liquiritinapioside, and ononin), liquiritigenin, tetrahydroxymethoxychalcone, and licochalcone B were found to enhance myoblast proliferation and differentiation, and myofiber diameters in injured muscles were wider with the liquiritigenin than the non-treated one. Computational analysis showed these compounds are non-toxic and possess good drug-likeness properties. These findings suggest that G. uralensis-extracted components might be useful therapeutic agents for the management of muscle-associated diseases.

Highlights

  • The expressions of atrophy and protein degradation related marker genes (Atrogin1 and MurF1) were lower in cells treated with G. uralensis crude water extract (CWE) than in non-treated controls (Figure 1C). These results show that G. uralensis CWE induced myoblast proliferation and differentiation by enhancing the expressions of myogenic genes and inhibiting atrophy-related genes expression

  • EtOAc, and BuOH fractions respect to control (Figure 3B). These results show that the the EX, EtOAc, and BuOH fractions of G. uralensis CWE enhance myoblast proliferation

  • We found that extracts of G. uralensis enhanced the proliferation and differentiation of C2C12 myoblasts, and that pre-treatment with G. uralensis extracts enhanced muscle regenerative ability in a CTX-induced mouse model of muscle injury

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Summary

Introduction

Skeletal muscle is composed of multinucleated myofibers and accounts for about half of the total body weight [1]. Myogenesis refers to myofiber producing processes such as those that occur during embryogenesis, postnatal growth, and muscle tissue regeneration [2]. Post-injury repair of skeletal muscle involves a series of complex events, which can be broadly categorized into three steps. The first involves the activation of quiescent muscle satellite cells (MSCs). The step involves myoblasts proliferation, which leads to the expansion of the progenitor cell population [5]. The final step involves withdrawal of proliferating myoblasts from the cell cycle and their terminal differentiation. MSC differentiation is essential for skeletal muscle regeneration and is regulated by interactions between

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