Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities

Yuling Yang; Xueyuan Yang; Xuke Zhang; Ziteng Song; Feng Liu; Yue Liang; Jie Zhang; Da-Qing Jin; Jing Xu; Dongho Lee; Muhetaer Tuerhong; Yasushi Ohizumi; Yuanqiang Guo

doi:10.1016/j.bioorg.2019.03.022

Bioactive terpenoids from Euonymus verrucosus var. pauciflorus showing NO inhibitory activities

Bioorg Chem. 2019 Jun:87:447-456. doi: 10.1016/j.bioorg.2019.03.022. Epub 2019 Mar 15.

Authors

Yuling Yang¹, Xueyuan Yang¹, Xuke Zhang¹, Ziteng Song¹, Feng Liu¹, Yue Liang¹, Jie Zhang², Da-Qing Jin³, Jing Xu⁴, Dongho Lee⁵, Muhetaer Tuerhong⁶, Yasushi Ohizumi⁷, Yuanqiang Guo⁸

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
² Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, People's Republic of China.
³ School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
⁴ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address: xujing611@nankai.edu.cn.
⁵ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
⁶ College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People's Republic of China.
⁷ Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai 989-3201, Japan.
⁸ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China. Electronic address: victgyq@nankai.edu.cn.

PMID: 30925429
DOI: 10.1016/j.bioorg.2019.03.022

Abstract

In our continuous search for new nitric oxide (NO) inhibitory compounds as potential anti-inflammatory agents or lead compounds for inflammatory diseases, the chemical constituents of Euonymus verrucosus var. pauciflorus were investigated, leading to the isolation of eleven terpenoids including six new diterpenoids, designated as euonymupenes A-F. The structures were elucidated on the basis of NMR and ECD data analysis. Euonymupenes A, C, and F feature rare labdane-type norditerpenoid skeletons. The NO inhibitory effects were evaluated and all of the isolates were found to inhibit lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells. Western blotting analysis indicated that the most active compound (5) can regulate iNOS (inducible nitric oxide synthase) expression. The further molecular docking studies exhibited the affinities of bioactive compounds with iNOS.

Keywords: Celastraceae; Euonymus verrucosus var. pauciflorus; NO inhibitory activities; Norditerpenoids; iNOS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Density Functional Theory
Dose-Response Relationship, Drug
Euonymus / chemistry*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Molecular Docking Simulation
Molecular Structure
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Structure-Activity Relationship
Terpenes / chemistry
Terpenes / isolation & purification
Terpenes / pharmacology*

Substances

Lipopolysaccharides
Terpenes
Nitric Oxide