Chemical constituents and synergistic anti-gout studies on Eurycoma longifolia and potential mechanisms evaluation based on systemic analysis approach

Bioorg Chem. 2019 Nov;92:103302. doi: 10.1016/j.bioorg.2019.103302. Epub 2019 Sep 17.

Abstract

37 compounds mainly including triterpenoids with the quassinoid skeleton and β-carboline alkaloids have been isolated from the roots of Eurycoma longifolia Jack (EL), which has been used as traditional medicine for a long history. It has been demonstrated that the total extracts from EL could significantly inhibit the joint swelling in MSU-induced acute gout arthritis rat model at middle and high doses (P < 0.05, P < 0.01), as meanwhile, better performance than that of positive control (P < 0.05, P < 0.01) has been observed at the dose of 10 g/kg. Aiming to search potential compounds and probable mechanisms, network pharmacology, molecular docking and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, leading to the hypothesis of 17 targets related to different pathogenesis of gout and 5 potential compounds (C36, C107, C124, C125 and C130) among 156 selected compounds, playing synergetic role with multiple targets. Instead of the guiding ideology of "a gene, a drug, a disease", varieties of compounds but not a single one from EL display holistic performance through multiple pathways with multi-targets. It was noteworthy that Xanthine dehydrogenase/oxidase (XDH), Prostaglandin G/H synthase 2 (PTGS2), Fatty acid-binding protein, liver (FABP1), Purine nucleoside phosphorylase (PNP), and Peroxisome proliferator activated receptor alpha (PPARA) were the key targets with intensely interaction. Furthermore, the functional enrichment analysis indicated that EL probably produced the gout protection effects by synergistic regulation in multiple biological pathways, including Toll-like receptor signaling pathway, MAPK signaling pathway, and NOD-like receptor signaling pathway, etc.

Keywords: Eurycoma longifolia; Gout; KEGG pathway enrichment analysis; Molecular docking; Network pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / therapeutic use*
  • Animals
  • Arthritis, Gouty / chemically induced
  • Arthritis, Gouty / drug therapy*
  • Coumarins / chemistry
  • Coumarins / isolation & purification
  • Coumarins / therapeutic use*
  • Dose-Response Relationship, Drug
  • Eurycoma / chemistry*
  • Molecular Docking Simulation
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Triterpenes / chemistry
  • Triterpenes / isolation & purification
  • Triterpenes / therapeutic use*
  • Uric Acid

Substances

  • Alkaloids
  • Coumarins
  • Plant Extracts
  • Triterpenes
  • Uric Acid