Benzoylmesaconine mitigates NLRP3 inflammasome-related diseases by reducing intracellular K+ efflux and disrupting NLRP3 inflammasome assembly

  • Phytomedicine. 2024 Dec:135:156154. doi: 10.1016/j.phymed.2024.156154.
Zhongyun Zhang  1 ,  Chen Wu  1 ,  Zilu Bao  1 ,  Zhaoxiang Ren  1 ,  Min Zou  1 ,  Shuhui Lei  1 ,  Kaiqun Liu  1 ,  Xukun Deng  1 ,  Shijin Yin  1 ,  Zhaohua Shi  2 ,  Liqin Zhang  3 ,  Zhou Lan  4 ,  Lvyi Chen  5
Affiliations
  • 1. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
  • 2. School of Pharmacy, Hubei University of Chinese Medicine, Wuhan China.
  • 3. The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, 2 Zheshan West Road, Wuhu 241002, China.
  • 4. School of Pharmacy, Hubei University of Chinese Medicine, Wuhan China. Electronic address: [email protected].
  • 5. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China. Electronic address: [email protected].
PMID: 39447229 DOI: 10.1016/j.phymed.2024.156154
Abstract

Background: Benzoylmesaconine (BMA), a major alkaloid derived from the traditional Chinese medicine Aconitum carmichaeli Debx, exhibits potent anti-inflammatory properties. However, the precise mechanism underlying its action remains unclear.

Purpose: This study aimed to investigate the inhibitory mechanism of BMA on the NLRP3 inflammasome and assess its therapeutic efficacy in NLRP3-related metabolic diseases.

Methods: A classic NLRP3 inflammasome-activated bone marrow-derived macrophage (BMDM) model was established to evaluate BMA's effects on NLRP3 upstream and downstream protein expression, as well as Pyroptosis. Two distinct animal disease models, MSU-induced gouty arthritis and DSS-induced colitis, were utilized to validate BMA's anti-inflammatory activity in vivo.

Results: In vitro findings revealed that BMA can suppress NLRP3 inflammasome activation by inhibiting interleukin-1β (IL-1β) secretion and GSDMD-N protein expression. This mechanism involved blocking intracellular K+ efflux and interfering with the formation of NLRP3 inflammasomes. In vivo studies demonstrated that BMA significantly alleviated inflammatory symptoms in MSU-induced acute gout and DSS-induced colitis models.

Conclusion: These findings suggest that BMA effectively inhibits the activation of the NLRP3 signaling pathway through dual mechanisms: reducing intracellular K+ efflux and disrupting NLRP3 inflammasome assembly. This multifaceted action highlights the therapeutic potential of BMA for NLRP3-related diseases.

Keywords
Benzoylmesaconine; Colitis; Gout; K(+)efflux; NLRP3 inflammasome.
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