2. Academic Validation
  3. Natural soluble epoxide hydrolase inhibitors from Inula helenium and their interactions with soluble epoxide hydrolase

Natural soluble epoxide hydrolase inhibitors from Inula helenium and their interactions with soluble epoxide hydrolase

  • Int J Biol Macromol. 2020 Apr 29:S0141-8130(20)33090-7. doi: 10.1016/j.ijbiomac.2020.04.227.
Xin He 1,  Wen-Yu Zhao 1,  Bo Shao 1,  Bao-Jing Zhang 1,  Tian-Tian Liu 1,  Cheng-Peng Sun 2,  Hui-Lian Huang 3,  Jia-Rong Wu 4,  Jia-Hao Liang 5,  Xiao-Chi Ma 6
Affiliations

Affiliations

  • 1 College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China.
  • 2 College of Pharmacy, College (Institute) of Integrative Medicine, Dalian Medical University, Dalian, China. Electronic address: [email protected].
  • 3 Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
  • 4 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • 5 Zhendong Pharmaceutical Research Institute Co. Ltd., Changzhi, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
  • 6 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: [email protected].
PMID: 32360461 DOI: 10.1016/j.ijbiomac.2020.04.227
Abstract

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 (IC50) from 5.88 ± 0.97 μM to 11.63 ± 0.58 μM. 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 μM, respectively, and linoleic acid (3) was a competitive type inhibitor with a Ki values of 3.52 μM. 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.

Keywords

Kinetics; Molecular stimulation; Soluble epoxide hydrolase.

Figures
Products