Screening of soluble epoxide hydrolase inhibitory ingredients from traditional Chinese medicines for anti-inflammatory use

Jun Yan Liu, Christophe Morisseau, Huazhang Huang, Bruce D. Hammock

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Ethnopharmacological relevance Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. Aim of the study To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo. Materials and methods In vitro inhibition assay of the sEH was conducted for the methanol and ethanol extracts of 27 anti-inflammatory TCMs. Two potent extracts were subject to further separation guided by bioassay to afford promising AI against sEH in vitro [Fr.5 of the crude ethanol extract of Rhizoma coptidis (FFCERC)]. Finally, the in vivo anti-inflammatory effect and sEH inhibitory potency of FFCERC was evaluated in a lipopolysacchride (LPS)-challenged murine model of acute systemic inflammation. The inflammatory status was characterized by the inflammatory cytokines TNF-α and interleukin-6 (IL-6) and sEH inhibitory function was evaluated by the plasma levels of epoxyeicosantrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs), which are the sEH mediated substrates and products, respectively. Results At the concentration of 25 µg/mL, the crude ethanol extracts of 6 TCMs including Herba Asari, Radix Polygalae, Fructus Amomi, Radix Astragali, Radix Scutellariae, and Rhizoma Coptidis were potent against sEH. The crude extracts of Herba Asari and Rhizoma Coptidis were selected for further separation to afford FFCERC as the most promising AI for in vivo evaluation. Oral administration of FFCERC attenuated the significant increase in TNF-α and IL-6 caused by LPS challenge in a dose-dependent manner. In parallel, oral administration of FFCERC shifted the changes in plasma levels of EETs and DHETs caused by LPS-challenge like a synthetic sEH inhibitor. Conclusions A sEH inhibitory AI from Rhizoma Coptidis is anti-inflammatory and the inhibition of sEH contributes to this biological effect, indicating that sEH may be at least one of multiple therapeutic targets for relevant TCMs.

Original languageEnglish (US)
Pages (from-to)475-482
Number of pages8
JournalJournal of Ethnopharmacology
Volume194
DOIs
StatePublished - Dec 24 2016

Keywords

  • Anti-inflammation
  • Cytokines
  • Eicosanoids
  • Rhizoma Coptidis
  • Soluble epoxide hydrolase (sEH)

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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