Isolation and Characterization of Compounds from Glycyrrhiza uralensis as Therapeutic Agents for the Muscle Disorders

Int J Mol Sci. 2021 Jan 16;22(2):876. doi: 10.3390/ijms22020876.

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.

Keywords: Glycyrrhiza uralensis; bioactive compounds; muscle regeneration; skeletal muscle.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Chalcones / therapeutic use
  • Flavanones / chemistry
  • Flavanones / pharmacology
  • Flavanones / therapeutic use
  • Glycyrrhiza uralensis / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscular Atrophy / drug therapy*
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Myostatin / genetics
  • Myostatin / metabolism
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Chalcones
  • Flavanones
  • Myostatin
  • Plant Extracts
  • 3-nitrotyrosine
  • Tyrosine
  • liquiritigenin