NO inhibitory phytochemicals as potential anti-inflammatory agents from the twigs of Trigonostemon heterophyllus

Yaru Xi; Lijun An; Xueyuan Yang; Ziteng Song; Jie Zhang; Muhetaer Tuerhong; Da-Qing Jin; Yasushi Ohizumi; Dongho Lee; Jing Xu; Yuanqiang Guo

doi:10.1016/j.bioorg.2019.03.029

NO inhibitory phytochemicals as potential anti-inflammatory agents from the twigs of Trigonostemon heterophyllus

Bioorg Chem. 2019 Jun:87:417-424. doi: 10.1016/j.bioorg.2019.03.029. Epub 2019 Mar 15.

Authors

Yaru Xi¹, Lijun An¹, Xueyuan Yang¹, Ziteng Song¹, Jie Zhang², Muhetaer Tuerhong³, Da-Qing Jin⁴, Yasushi Ohizumi⁵, Dongho Lee⁶, Jing Xu⁷, 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, China.
² Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, China.
³ College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, China.
⁴ School of Medicine, Nankai University, Tianjin 300071, China.
⁵ Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai 989-3201, Japan.
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, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: xujing611@nankai.edu.cn.
⁸ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: victgyq@nankai.edu.cn.

PMID: 30921743
DOI: 10.1016/j.bioorg.2019.03.029

Abstract

Studies on the relationship of nitric oxide (NO) and inflammation have revealed that compounds with NO inhibitory effects are potentially useful for inflammation and related inflammatory disorders. A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of two new cleistanthane diterpenoids (1 and 2) and 11 known terpenoids (3-13) from Trigonostemon heterophyllus. The structures of these terpenoids were established by analysis of their NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 possess rare 3,4-seco-cleistanthane diterpenoid skeletons. All of the isolates were evaluated biologically for their NO inhibitory effects in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells and compounds 1, 6, and 8-10 showed strong NO inhibitory effects with IC₅₀ values less than 40 μM. Using Western blotting experiments and molecular docking, the possible mechanism of NO inhibition was investigated.

Keywords: Cleistanthane diterpenoids; Inflammation; Molecular docking; NO inhibitors; Trigonostemon heterophyllus.

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
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / chemistry
Drugs, Chinese Herbal / isolation & purification
Drugs, Chinese Herbal / pharmacology*
Euphorbiaceae / chemistry*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Molecular Docking Simulation
Molecular Structure
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Phytochemicals / chemistry
Phytochemicals / isolation & purification
Phytochemicals / pharmacology*
Plant Stems / chemistry*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Drugs, Chinese Herbal
Lipopolysaccharides
Phytochemicals
Nitric Oxide