Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury.
10.1016/S1875-5364(17)30055-9
- Author:
Yi MOU
1
;
Yan-Lin JIAN
1
;
Tong CHEN
2
;
Zhang-Jian HUANG
1
;
Yi-Xue QIAO
1
;
Si-Xun PENG
1
;
Da-Yong ZHANG
1
;
Hui JI
2
;
Yi-Hua ZHANG
3
Author Information
1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
2. State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
3. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zyhtgd@163.com.
- Publication Type:Journal Article
- Keywords:
Acute lung injury;
Anti-inflammation;
Lactone;
Oleanolic acid
- MeSH:
Acute Lung Injury;
drug therapy;
genetics;
immunology;
Animals;
Anti-Inflammatory Agents;
administration & dosage;
chemical synthesis;
Bronchoalveolar Lavage Fluid;
immunology;
Cyclooxygenase 2;
genetics;
immunology;
Female;
Humans;
Interleukin-1beta;
genetics;
immunology;
Interleukin-6;
genetics;
immunology;
Lipopolysaccharides;
adverse effects;
Lung;
drug effects;
immunology;
Macrophages;
drug effects;
immunology;
Male;
Mice;
Mice, Inbred BALB C;
Neutrophils;
drug effects;
immunology;
Oleanolic Acid;
administration & dosage;
analogs & derivatives;
chemical synthesis;
Peroxidase;
genetics;
immunology;
RAW 264.7 Cells;
Tumor Necrosis Factor-alpha;
genetics;
immunology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2017;15(5):347-354
- CountryChina
- Language:English
-
Abstract:
The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.
