期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 73, 期 10, 页码 1319-1329出版社
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgab074
关键词
acute lung injury; beta-caryophyllene; inflammation; transforming growth factor beta-activated kinase 1; mitogen-activated protein kinase phosphatase 1; lipopolysaccharide
资金
- National Natural Science Foundation of China [81573438, 81673791, 81773741, 81973329]
- Key Research and Development Program of Anhui Province [1804h08020287]
The study shows that BCP significantly alleviates LPS-induced ALI by reducing neutrophil infiltration and cytokine production. In vitro, BCP was found to reduce the expression of IL-6, IL-1β, and TNF-α, and suppress the MAPK signaling pathway in BMDMs.
Objectives: Acute lung injury (ALI) is a pulmonary manifestation of an acute systemic inflammatory response, which is associated with high morbidity and mortality. Accordingly, from the perspective of treating ALI, it is important to identify effective agents and elucidate the underlying modulatory mechanisms. beta-Caryophyllene (BCP) is a naturally occurring bicyclic sesquiterpene that has anti-cancer and anti-inflammatory activities. However, the effects of BCP on ALI have yet to be ascertained. Methods: ALI was induced intratracheally, injected with 5 mg/kg LPS and treated with BCP. The bone marrow-derived macrophages (BMDMs) were obtained and cultured then challenged with 100 ng/ml LPS for 4 h, with or without BCP pre-treatment for 30 min. Key findings: BCP significantly ameliorates LPS-induced mouse ALI, which is related to an alleviation of neutrophil infiltration and reduction in cytokine production. In vitro, BCP was found to reduce the expression of interleukin-6, interleukin-1 beta and tumour necrosis factor-alpha, and suppresses the MAPK signalling pathway in BMDMs, which is associated with the inhibition of TAK1 phosphorylation and an enhancement of MKP-1 expression. Conclusions: Our data indicate that BCP protects against inflammatory responses and is a potential therapeutic agent for the treatment of LPS-induced acute lung injury.
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