Synthesis and inhibitory effect of cis-guggulsterone on lipopolysaccharide-induced production of nitric oxide in macrophages

Jun Yeon Park; Jae Wook Lee; Chang-Ho Lee; Hae-Jeung Lee; Ki Sung Kang

doi:10.1016/j.bmcl.2020.126962

Synthesis and inhibitory effect of cis-guggulsterone on lipopolysaccharide-induced production of nitric oxide in macrophages

Bioorg Med Chem Lett. 2020 Mar 1;30(5):126962. doi: 10.1016/j.bmcl.2020.126962. Epub 2020 Jan 8.

Authors

Jun Yeon Park¹, Jae Wook Lee², Chang-Ho Lee³, Hae-Jeung Lee⁴, Ki Sung Kang⁵

Affiliations

¹ Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Republic of Korea.
² Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea; Convergent Research Center for Dementia, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology, Daejeon 34113, Republic of Korea.
³ Research Group of Functional Food Materials, Korea Food Research Institute, Wanju 55365, Republic of Korea.
⁴ Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea. Electronic address: skysea1010@gmail.com.
⁵ College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea. Electronic address: kkang@gachon.ac.kr.

PMID: 31980338
DOI: 10.1016/j.bmcl.2020.126962

Abstract

Guggulsterone is a bioactive plant sterol naturally found in migratory plants. It exists in various forms, and its active compounds include the isomers cis-guggulsterone (E-GS) and trans-guggulsterone (Z-GS). In this study, the anti-inflammatory effects of these two isomeric pregnadienedione steroids were investigated against lipopolysaccharide-induced inflammatory reaction in RAW264.7 mouse macrophages. Our results showed that both guggulsterones inhibited the production of NO in macrophages treated with lipopolysaccharide, with IC50 values ranging from 3.0 to 6.7 μM. E-GS exerted higher efficacy than Z-GS, and its anti-inflammatory effects was mediated through inhibition of iNOS and COX-2 expression.

Keywords: COX-2; Guggulsterone; Inflammation; RAW264.7; iNOS.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / pharmacology*
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / pharmacology*
Down-Regulation / drug effects
Escherichia coli / chemistry
Lipopolysaccharides / pharmacology
Macrophages / drug effects*
Mice
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide Synthase Type II / antagonists & inhibitors
Pregnenediones / chemical synthesis
Pregnenediones / pharmacology*
RAW 264.7 Cells
Stereoisomerism

Substances

Anti-Inflammatory Agents
Cyclooxygenase 2 Inhibitors
Lipopolysaccharides
Pregnenediones
Nitric Oxide
pregna-4,17-diene-3,16-dione
Nitric Oxide Synthase Type II
Nos2 protein, mouse
Ptgs2 protein, mouse
Cyclooxygenase 2