Maackiain, a compound derived from Sophora flavescens, increases IL-1β production by amplifying nigericin-mediated inflammasome activation

  • FEBS Open Bio. 2020 Aug;10(8):1482-1491. doi: 10.1002/2211-5463.12899.
Jin-Won Huh  1 ,  Jung-Hoon Lee  1 ,  Eekhyoung Jeon  1 ,  Hyung Won Ryu  2 ,  Sei-Ryang Oh  2 ,  Kyung-Seop Ahn  2 ,  Hyun Sik Jun  1 ,  Un-Hwan Ha  1
Affiliations
  • 1. Department of Biotechnology and Bioinformatics, Korea University, Sejong, Korea.
  • 2. Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Korea.
PMID: 32428336 DOI: 10.1002/2211-5463.12899
Abstract

Sophora flavescens is used as a traditional herbal medicine to modulate inflammatory responses. However, little is known about the impact of (-)-maackiain, a compound derived from S. flavescens, on the activation of inflammasome/Caspase-1, a key factor in interleukin-1β (IL-1β) processing. Here, we report that (-)-maackiain potently amplified Caspase-1 cleavage in macrophages in response to nigericin (Nig). In macrophages primed with either lipopolysaccharide or monophosphoryl lipid A, Nig-mediated Caspase-1 cleavage was also markedly promoted by (-)-maackiain. Notably, (-)-maackiain induced the production of vimentin, an essential mediator for the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome, thereby contributing to promotion of the formation of the inflammasome complex to activate Caspase-1. Taken together, our data suggest that (-)-maackiain exerts an immunostimulatory effect by promoting IL-1β production via activation of the inflammasome/Caspase-1 pathway. Thus, the potent inflammasome-activating effect of (-)-maackiain may be clinically useful as an acute immune-stimulating agent.

Keywords
Sophora flavescens; (-)-maackiain; inflammasome; monophosphoryl lipid A; nigericin.
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