Pteryxin attenuates LPS-induced inflammatory responses and inhibits NLRP3 inflammasome activation in RAW264.7 cells

Pteryxin is a natural coumarin compound that is found in “Qianhu”, a traditional Chinese medicine, which possesses heat-clearing and detoxifying functions according to the theory of Traditional Chinese Medicine. Despite its medicinal effects, its anti-inflammatory and mechanisms of actions have not...

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Published in:Journal of ethnopharmacology 2022-02, Vol.284, p.114753-114753, Article 114753
Main Authors: Zhen, Dong, Xuan, Tian-qi, Hu, Boqin, Bai, Xue, Fu, Dan-ni, Wang, Yu, Wu, Yun, Yang, Jingfeng, Ma, Qianqian
Format: Article
Language:English
Subjects:
Animals
Anti-inflammatory activity
Anti-Inflammatory Agents - pharmacology
Coumarins - pharmacology
Female
Inflammasomes - metabolism
Inflammation - drug therapy
Lipopolysaccharides
Macrophages - drug effects
Macrophages - pathology
Male
MAP Kinase Signaling System - drug effects
MAPK
Mice
NF-kappa B - metabolism
NF-κB
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
NLRP3 inflammasome
Pteryxin
RAW 264.7 Cells
Zebrafish
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Summary:Pteryxin is a natural coumarin compound that is found in “Qianhu”, a traditional Chinese medicine, which possesses heat-clearing and detoxifying functions according to the theory of Traditional Chinese Medicine. Despite its medicinal effects, its anti-inflammatory and mechanisms of actions have not been established. This study aims to evaluate the anti-inflammatory property and reveal the possible anti-inflammatory mechanisms of pteryxin. LPS-induced RAW 264.7 macrophages and LPS-induced zebrafish model were used for the anti-inflammatory activity determination of pteryxin. The level of NO, PEG2, TNF-α and IL-6 were measured by ELISA. The accumulation of NO and ROS was stained and observed by a fluorescence microscopy. The nuclear translocation of NF-κB p65 and formation of NLRP3 inflammasome complex in LPS-induced RAW 264.7 macrophage cells were analyzed by immunofluorescence assay. The expression level of iNOS, IL-6, COX-2, TNF-α, p-p38, p38, ERK, JNK, p-ERK, p-JNK, IKK, IκB-α, p-IKK, p-IκB-α, p65, NLRP3, p-p65, Caspase 1 (p 20), ASC, and GAPDH were determined by Western blotting. Lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) secretions were found to be downregulated by pteryxin. Moreover, pteryxin significantly suppressed inflammatory factor secretion in LPS-treated RAW 264.7 cells. Mechanistically, pteryxin significantly downregulated NF-κB/MAPK activation. Moreover, pteryxin inhibited caspase-1 and NLRP3 activation and formation of ASC specks in RAW 264.7 cells, implying that pteryxin inhibits inflammasome assembly, which is a signal for NLRP3 inflammasome activation. In conclusion, pteryxin blocks NF-κB/MAPK signaling, and suppresses the initiation and activation of NLRP3 thereby preventing inflammation. Pteryxin is a potential treatment option for inflammatory-related diseases. [Display omitted] •Pteryxin inhibits LPS-induced inflammatory responses.•Anti-inflammatory effects of pteryxin are associated with inhibited NF-κB and MAPK signaling pathway.•Pteryxin could suppresses the priming and activating steps of NLRP3 inflammasomes.
ISSN:0378-8741
1872-7573
DOI:10.1016/j.jep.2021.114753