Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome

Acta Pharmaceutica Sinica. B
Zhilei WangZhaofang Bai

Abstract

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1β production induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor ...Continue Reading

Citations

Jun 13, 2020·Free Radical Research·Zhengjun WangLi Liu
May 16, 2020·Frontiers in Physiology·Zhenhong FuYundai Chen
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivan Qi Han NguiRajaraman Eri
Nov 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xinming WangWei Wei
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Wan-Li JiangSong-Ping Xie
Dec 23, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hongbin LiuZhaofang Bai
Feb 5, 2021·Biomedicines·Baolong Liu, Jiujiu Yu
Mar 6, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Xiaobing LinMing Yan
Jun 6, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nadire Özenver, Thomas Efferth
Jun 10, 2021·In Vitro Cellular & Developmental Biology. Animal·Feifei ShaoZhihui Guan
Aug 17, 2020·Neuroscience·Yi-Qun YanBao-Rong Zhang

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Methods Mentioned

BETA
PMA
electrophoresis
Assay
ELISA

Software Mentioned

GraphPad
Prism

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