title: Discovery of soluble epoxide hydrolase inhibitors from natural products.
abstract: With the goal of developing soluble epoxide hydrolase (sEH) inhibitors with novel chemical structures, the sEH inhibitory activities of 30 natural compounds were evaluated using both a fluorescent substrate, 3-phenyl-cyano(6-methoxy-2-naphthalenyl)methyl ester- 2-oxiraneacetic acid, and a physiological substrate, 14,15-epoxyeicosatrienoic acid. To evaluate the selectivity of sEH inhibition, the inhibition of microsomal epoxide hydrolase (mEH), which plays a critical role in detoxification of toxic epoxides, was determined using human liver microsomes. Honokiol and β-amyrin acetate, isolated from Magnolia officinalis and Acer mandshuricum, respectively, displayed strong inhibition of sEH activity, with respective IC50 values of 0.57 μM and 3.4 μM determined using the fluorescent substrate, and 1.7 μM and 6.1 μM determined using 14,15-epoxyeicosatrienoic acid. mEH activity was decreased to 49% or 61% of control activity by 25 μM honokiol or β-amyrin acetate, respectively. These results suggest that β-amyrin acetate and honokiol exhibit sEH inhibitory activity, although their sEH selectivity should be improved.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Gwan Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: Bio-Evaluation Center, KRIBB, Ochang, Chungbuk 363-883, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: TKM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: yhk@cnu.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: sangkim@cnu.ac.kr.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005470:Fluorometry; D017705:Lignans / Q000302:isolation & purification* / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001688:Biological Products; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D004851:Epoxide Hydrolases; D017705:Lignans; D009828:Oleanolic Acid; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C000265:beta-amyrin acetate
keywords: Honokiol; Selectivity; Soluble epoxide hydrolase; β-Amyrin acetate