NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum

Lijun An; Yue Liang; Xueyuan Yang; Huimei Wang; Jie Zhang; Muhetaer Tuerhong; Dihua Li; Chunyan Wang; Dongho Lee; Jing Xu; Ling Shuai; Jin Jin; Yuanqiang Guo

doi:10.1016/j.bioorg.2019.103237

NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum

Bioorg Chem. 2019 Nov:92:103237. doi: 10.1016/j.bioorg.2019.103237. Epub 2019 Sep 4.

Authors

Lijun An¹, Yue Liang¹, Xueyuan Yang¹, Huimei Wang¹, Jie Zhang², Muhetaer Tuerhong³, Dihua Li⁴, Chunyan Wang⁵, Dongho Lee⁶, Jing Xu⁷, Ling Shuai¹, Jin Jin¹, Yuanqiang Guo⁸

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, 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 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.
⁴ Tianjin Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Nankai Hospital Affiliated to Nankai University, Tianjin 300100, People's Republic of China.
⁵ Tianjin Second People's Hospital, Tianjin 300192, People's Republic of China.
⁶ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
⁷ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China. Electronic address: xujing611@nankai.edu.cn.
⁸ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, People's Republic of China. Electronic address: victgyq@nankai.edu.cn.

PMID: 31536954
DOI: 10.1016/j.bioorg.2019.103237

Abstract

Two new ent-atisane-type diterpenoids (1 and 2), three new lathyrane-type diterpenoids (3-5), and seven known analogues (6-12) were isolated from Euphorbia antiquorum. The structures of these diterpenoids were established by analysis of their NMR, MS, and electronic circular dichroism data. The anti-inflammatory activities were evaluated biologically and compounds 1, 4, 7, 8, and 10 displayed strong NO inhibitory effects with IC₅₀ values less than 40 μM. The potential anti-inflammatory mechanism was also investigated using molecular docking and Western blotting.

Keywords: Diterpenoids; Euphorbia antiquorum; Inflammation; Molecular docking; NO inhibitory effects.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Cell Line
Cyclooxygenase 2 / genetics
Diterpenes / chemistry
Diterpenes / isolation & purification
Diterpenes / pharmacology*
Euphorbia / chemistry*
Gene Expression / drug effects
Mice
Microglia / drug effects
Microglia / metabolism
Molecular Docking Simulation
Molecular Structure
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide Synthase Type II / genetics
Plant Stems / chemistry

Substances

Anti-Inflammatory Agents
Diterpenes
Nitric Oxide
Nitric Oxide Synthase Type II
Nos2 protein, mouse
Ptgs2 protein, mouse
Cyclooxygenase 2