Evaluation of LPS-Induced Acute Lung Injury Attenuation in Rats by Aminothiazole-Paeonol Derivatives

Autor: Jui Ping Li, Su Chin Huang, Ying Pei Huang, Chi Yu Yang, Yu Wen Hung, Kee Ching Jeng, Ming Hua Hsu, Nai Chun Huang, Pin Kuei Fu, Hong Chuang, Jen Kun Chen
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
ARDS
Pathology
Moutan Cortex Radicis
Anti-Inflammatory Agents
Pharmaceutical Science
Pharmacology
aminothiazole-paeonol derivatives
Analytical Chemistry
chemistry.chemical_compound
Drug Discovery
Medicine
Chemokine CCL2
medicine.diagnostic_test
medicine.anatomical_structure
Neutrophil Infiltration
Chemistry (miscellaneous)
Molecular Medicine
medicine.symptom
Bronchoalveolar Lavage Fluid
medicine.medical_specialty
Inflammation
Lung injury
Article
lcsh:QD241-441
03 medical and health sciences
anti-inflammation agents
lcsh:Organic chemistry
Animals
Physical and Theoretical Chemistry
A549 cell
Lung
Interleukin-6
business.industry
Monocyte
Organic Chemistry
paeonol
acute lung injury
acute respiratory distress syndrome
Acetophenones
medicine.disease
Rats
Thiazoles
030104 developmental biology
Bronchoalveolar lavage
chemistry
Paeonol
business
Zdroj: Molecules; Volume 22; Issue 10; Pages: 1605
Molecules, Vol 22, Iss 10, p 1605 (2017)
Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
ISSN: 1420-3049
DOI: 10.3390/molecules22101605
Popis: Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol (4) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents.
Databáze: OpenAIRE
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