Bioactive sesquiterpene coumarins from the resin of Ferula sinkiangensis targeted on over-activation of microglia

Tingting Guo; Di Zhou; Yanqiu Yang; Xueni Zhang; Gang Chen; Bin Lin; Yu Sun; Hui Ni; Jingyu Liu; Yue Hou; Ning Li

doi:10.1016/j.bioorg.2020.104338

Bioactive sesquiterpene coumarins from the resin of Ferula sinkiangensis targeted on over-activation of microglia

Bioorg Chem. 2020 Nov:104:104338. doi: 10.1016/j.bioorg.2020.104338. Epub 2020 Oct 8.

Authors

Tingting Guo¹, Di Zhou¹, Yanqiu Yang², Xueni Zhang¹, Gang Chen¹, Bin Lin³, Yu Sun⁴, Hui Ni⁴, Jingyu Liu², Yue Hou⁵, Ning Li⁶

Affiliations

¹ School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China.
² College of Life and Health Sciences, Northeastern University, Shenyang 110004, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, China.
³ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁴ XinJiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China.
⁵ College of Life and Health Sciences, Northeastern University, Shenyang 110004, China; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, China. Electronic address: houyue@mail.neu.edu.cn.
⁶ School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, China. Electronic address: liningsypharm@163.com.

PMID: 33142410
DOI: 10.1016/j.bioorg.2020.104338

Abstract

Nine undescribed (1-4, 6-10) sesquiterpene coumarins, together with a new natural one (5) and ten known ones (11-20), were isolated from the low polarity fraction of the 95% ethanol extract of the resin of Ferula sinkiangensis. Their structures were elucidated based on the comprehensive analysis of HRESIMS, 1D and 2D NMR data. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. All the identified SCs were evaluated for their anti-neuroinflammatory activities in LPS-induced BV-2 cells. Ferusingensine G (8) displayed a significant inhibitory effect on nitric oxide (NO) production with an IC₅₀ value of 1.2 μM. The results suggested that natural SCs might be served as potential neuroinflammatory inhibitors.

Keywords: BV2 microglial cell; Ferula sinkiangensis; Neuroinflammation; Sesquiterpene coumarins.

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 Survival / drug effects
Cells, Cultured
Coumarins / chemistry
Coumarins / isolation & purification
Coumarins / pharmacology*
Dose-Response Relationship, Drug
Ferula / chemistry*
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Microglia / drug effects*
Microglia / metabolism
Molecular Docking Simulation
Molecular Structure
Nitric Oxide / antagonists & inhibitors
Nitric Oxide / biosynthesis
Resins, Plant / chemistry*
Sesquiterpenes / chemistry
Sesquiterpenes / isolation & purification
Sesquiterpenes / pharmacology*
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Coumarins
Lipopolysaccharides
Resins, Plant
Sesquiterpenes
Nitric Oxide