2. Academic Validation
  3. Brevilin A inhibits NLRP3 inflammasome activation in vivo and in vitro by acting on the upstream of NLRP3-induced ASC oligomerization

Brevilin A inhibits NLRP3 inflammasome activation in vivo and in vitro by acting on the upstream of NLRP3-induced ASC oligomerization

  • Mol Immunol. 2021 Jul;135:116-126. doi: 10.1016/j.molimm.2021.03.025.
Qin Qin 1,  Guang Xu 2,  Xiaoyan Zhan 2,  Zhilei Wang 3,  Yan Wang 4,  Hongbin Liu 3,  Xiaorong Hou 2,  Wei Shi 2,  Jianli Ma 5,  Zhaofang Bai 6,  Xiaohe Xiao 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Dali University, Dali, 671000, China; Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 2 Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 3 Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
  • 4 Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, 450046, China.
  • 5 Department of Pharmacy, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: weihai304@126.com.
  • 6 Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: baizf2008@hotmail.com.
  • 7 School of Pharmacy, Dali University, Dali, 671000, China; Department of Liver Diseases, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: pharmacy_302@126.com.
PMID: 33892379 DOI: 10.1016/j.molimm.2021.03.025
Abstract

Brevilin A (BA), is a natural biologically active ingredient derived from Centipeda minima with several reports of anti-cancer, while its anti-inflammatory activity is rarely reported. Current studies have found the dysregulated activation of NLRP3 inflammasome cause a variety of inflammatory diseases. Targeting the NLRP3 inflammasome contributes to the treatment of NLRP3-induced diseases. Here, we found that BA significantly attenuates the activation of Caspase-1 and the subsequent secretion of the interleukin-1β (IL-1β) in mouse macrophages and human THP-1 cells, showing the inhibitory effect of BA on the NLRP3 inflammasome activation. Moreover, BA specifically inhibits NLRs inflammasomes activation triggered by multi-stimuli, but it has no effect on the AIM2 inflammasome activation, indicating that BA is a specific inhibitor of the NLRs inflammasomes. Research on the mechanism found BA inhibits NLRP3 inflammasome activation by blocking the upstream of ASC oligomerization. Importantly, in vivo experiments showed that BA markedly reduces the secretion of IL-1β to suppress NLRP3 inflammasome in the LPS-induced inflammation and MSU-challenged peritonitis model. In conclusion, our experiments show that BA is an effective NLRP3 inflammasome inhibitor and can be regarded as a drug candidate for NLRP3 inflammasome-driven diseases.

Keywords

Brevilin A; Caspase-1; IL-1β; NLRP3 inflammasome; Septic shock.

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