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Phytomedicine 2019-Jul

Obovatol inhibits NLRP3, AIM2, and non-canonical inflammasome activation.

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Jeongeun Kim
Huijeong Ahn
Byung-Cheol Han
Hyunjung Shin
Jin-Chul Kim
Eui-Man Jung
Juyeol Kim
Heejung Yang
Jeonghyun Lee
Seung Kang

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Obovatol, a biphenolic chemical originating from Magnolia obovata, has been utilized as a traditional medicine for the treatment of inflammatory diseases. Inflammasome induces maturation of inflammatory cytokines in response to intracellular danger signals, and its dysregulation induces inflammatory diseases.The effect of obovatol on inflammasome activation has not been reported, although its anti-inflammatory properties have been studied.Obovatol was treated to macrophages with inflammasome triggers, and secretions of interleukin (IL)-1β, IL-18, and caspase-1 were measured as readouts of inflammasome activation. In addition, Asc pyroptosome formation, caspase-1 activity, and mitochondrial reactive oxygen species (ROS) production were analyzed in mechanical studies. Anti-inflammasome properties of obovatol were confirmed in an animal model.Obovatol inhibited NLRP3, AIM2, and non-canonical inflammasomes through inhibition of Asc pyroptosome formation and mitochondrial ROS generation. In addition, obovatol disrupted the priming step of inflammasome activation and inhibited transcription of inflammatory cytokines. In mice, obovatol attenuated serum IL-1β elevation in response to monosodium urate crystals.Obovatol is suggested as an inhibitor of NLRP3, AIM2, and non-canonical inflammasomes.

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