2. Academic Validation
  3. Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases

Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases

  • Pharmacol Res. 2021 Feb;164:105384. doi: 10.1016/j.phrs.2020.105384.
Hongbin Liu 1,  Xiaoyan Zhan 2,  Guang Xu 3,  Zhilei Wang 3,  Ruisheng Li 4,  Yan Wang 3,  Qin Qin 3,  Wei Shi 3,  Xiaorong Hou 3,  Ruichuang Yang 4,  Jian Wang 5,  Xiaohe Xiao 6,  Zhaofang Bai 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China; Department of Pharmacy, Hebei North University, Zhangjiakou, 075000, China.
  • 2 China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: [email protected].
  • 3 China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 4 Research Center for Clinical and Translational Medicine, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China.
  • 5 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: [email protected].
  • 6 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: [email protected].
  • 7 China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: [email protected].
PMID: 33352229 DOI: 10.1016/j.phrs.2020.105384
Abstract

NLRP3 inflammasome activation is implicated in the pathogenesis of a wide range of inflammatory diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. Here, we demonstrate that cryptotanshinone (CTS), a major component derived from the traditional medicinal herb Salvia miltiorrhiza Bunge, is a specific inhibitor for the NLRP3 inflammasome. Cryptotanshinone inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanistically, cryptotanshinone blocks Ca2+ signaling and the induction of mitochondrial Reactive Oxygen Species (mtROS), which are important upstream signals of NLRP3 inflammasome activation. In vivo, cryptotanshinone attenuates Caspase-1 activation and IL-1β secretion in mouse models of NLRP3 inflammasome-mediated diseases such as endotoxemia syndrome and methionine- and choline-deficient-diet-induced nonalcoholic steatohepatitis (NASH). Our findings suggest that cryptotanshinone may be a promising therapeutic agent for the treatment of NLRP3 inflammasome-mediated diseases.

Keywords

Cryptotanshinone; Cryptotanshinone (PubChem CID: 160254); Endotoxemia; NASH; NLRP3 inflammasome.

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