Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF- κ B and RhoA/ROCK Signaling Pathways

Biomed Res Int. 2021 Aug 9:2021:5561221. doi: 10.1155/2021/5561221. eCollection 2021.

Abstract

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Brucea / chemistry*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Dextran Sulfate / adverse effects*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Plant Oils / administration & dosage*
  • Plant Oils / chemistry
  • Plant Oils / pharmacology
  • Quassins / administration & dosage*
  • Quassins / pharmacology
  • Signal Transduction / drug effects*
  • Treatment Outcome
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • NF-kappa B
  • Plant Oils
  • Quassins
  • brusatol
  • Dextran Sulfate
  • rho-Associated Kinases
  • RhoA protein, mouse
  • rhoA GTP-Binding Protein