title: Screening of soluble epoxide hydrolase inhibitory ingredients from traditional Chinese medicines for anti-inflammatory use.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 25µg/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.
authors.affiliation: Center for Nephrology and Clinical Metabolomics, Division of Nephrology and Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Mid Yanchang Rd, Shanghai 200072, PR China; Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, United States. Electronic address: jyliu@tongji.edu.cn.
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, United States.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, United States.
authors.forename: Huazhang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Entomology and Nematology, UCD Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, United States.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D004851:Epoxide Hydrolases
keywords: Anti-inflammation; Cytokines; Eicosanoids; Rhizoma Coptidis; Soluble epoxide hydrolase (sEH)