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

Autor: Zhen D; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: dongzhen@imun.com., Xuan TQ; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: 1543505206@qq.com., Hu B; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: 839061084@qq.com., Bai X; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: bx_1226@163.com., Fu DN; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: fu_dan_ni@126.com., Wang Y; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: shen348@126.com., Wu Y; Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: wuyun1214@126.com., Yang J; College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: yangjf@imun.edu.cn., Ma Q; Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: maqq2020@126.com.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2022 Feb 10; Vol. 284, pp. 114753. Date of Electronic Publication: 2021 Oct 15.
DOI: 10.1016/j.jep.2021.114753
Abstrakt: Ethnopharmacological Relevance: 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.
Aim of This Study: This study aims to evaluate the anti-inflammatory property and reveal the possible anti-inflammatory mechanisms of pteryxin.
Material and Methods: 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, PEG 2 , 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.
Results: 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.
Conclusion: Pteryxin is a potential treatment option for inflammatory-related diseases.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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