PMID- 32360461 OWN - NLM STAT- Publisher LR - 20240227 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) DP - 2020 Apr 29 TI - Natural soluble epoxide hydrolase inhibitors from Inula helenium and their interactions with soluble epoxide hydrolase. LID - S0141-8130(20)33090-7 [pii] LID - 10.1016/j.ijbiomac.2020.04.227 [doi] AB - The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat inflammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of traditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium were isolated to obtain eight compounds, including 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concentration (IC(50)) from 5.88 +/- 0.97 muM to 11.63 +/- 0.58 muM. The inhibition kinetics suggested that 4H-tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constant (Ki) values of 7.02 and 6.57 muM, respectively, and linoleic acid (3) was a competitive type inhibitor with a Ki values of 3.52 muM. The potential interactions of 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by molecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - He, Xin AU - He X AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. FAU - Zhao, Wen-Yu AU - Zhao WY AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. FAU - Shao, Bo AU - Shao B AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. FAU - Zhang, Bao-Jing AU - Zhang BJ AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. FAU - Liu, Tian-Tian AU - Liu TT AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. FAU - Sun, Cheng-Peng AU - Sun CP AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. Electronic address: suncp146@163.com. FAU - Huang, Hui-Lian AU - Huang HL AD - Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China. FAU - Wu, Jia-Rong AU - Wu JR AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. FAU - Liang, Jia-Hao AU - Liang JH AD - Zhendong Pharmaceutical Research Institute Co. Ltd., Changzhi, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. FAU - Ma, Xiao-Chi AU - Ma XC AD - College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China. Electronic address: maxiaochi2019@163.com. LA - eng PT - Journal Article DEP - 20200429 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 SB - IM OTO - NOTNLM OT - Kinetics OT - Molecular stimulation OT - Soluble epoxide hydrolase COIS- Declaration of competing interest The authors declare no competing financial interest. EDAT- 2020/05/04 06:00 MHDA- 2020/05/04 06:00 CRDT- 2020/05/04 06:00 PHST- 2020/02/06 00:00 [received] PHST- 2020/03/15 00:00 [revised] PHST- 2020/04/25 00:00 [accepted] PHST- 2020/05/04 06:00 [entrez] PHST- 2020/05/04 06:00 [pubmed] PHST- 2020/05/04 06:00 [medline] AID - S0141-8130(20)33090-7 [pii] AID - 10.1016/j.ijbiomac.2020.04.227 [doi] PST - aheadofprint SO - Int J Biol Macromol. 2020 Apr 29:S0141-8130(20)33090-7. doi: 10.1016/j.ijbiomac.2020.04.227.