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

  • J Ethnopharmacol. 2022 Feb 10:284:114753. doi: 10.1016/j.jep.2021.114753.
Dong Zhen  1 ,  Tian-Qi Xuan  2 ,  Boqin Hu  3 ,  Xue Bai  4 ,  Dan-Ni Fu  5 ,  Yu Wang  6 ,  Yun Wu  7 ,  Jingfeng Yang  8 ,  Qianqian Ma  9
Affiliations
  • 1. 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: [email protected].
  • 2. 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: [email protected].
  • 3. 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: [email protected].
  • 4. 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: [email protected].
  • 5. 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: [email protected].
  • 6. 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: [email protected].
  • 7. Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: [email protected].
  • 8. College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China. Electronic address: [email protected].
  • 9. 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: [email protected].
PMID: 34662667 DOI: 10.1016/j.jep.2021.114753
Abstract

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, 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.

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.

Keywords
Anti-inflammatory activity; MAPK; NF-κB; NLRP3 inflammasome; Pteryxin.
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