Identification of Peucedanum japonicum Thunb. extract components and their protective effects against dexamethasone-induced muscle atrophy

Phytomedicine. 2024 Jun:128:155449. doi: 10.1016/j.phymed.2024.155449. Epub 2024 Feb 13.

Abstract

Background: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive.

Purpose: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy.

Methods: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively.

Results: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor.

Conclusion: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.

Keywords: 4-caffeoylquinic acid; Dexamethasone; Muscle atrophy; Peucedanum japonicum Thunb; Protein degradation.

MeSH terms

  • Animals
  • Apiaceae* / chemistry
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Dexamethasone* / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Muscle Fibers, Skeletal / drug effects
  • Muscular Atrophy* / chemically induced
  • Muscular Atrophy* / drug therapy
  • Myogenin / metabolism
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Quinic Acid / analogs & derivatives*
  • Quinic Acid / pharmacology
  • Tandem Mass Spectrometry

Substances

  • Dexamethasone
  • Plant Extracts
  • caffeoylquinic acid
  • Quinic Acid
  • Myogenin