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

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2024-10-23 DOI:10.1016/j.phymed.2024.156154

Zhongyun Zhang, Chen Wu, Zilu Bao, Zhaoxiang Ren, Min Zou, Shuhui Lei, Kaiqun Liu, Xukun Deng, Shijin Yin, Zhaohua Shi, Liqin Zhang, Zhou Lan, Lvyi Chen

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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.

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苯甲酰新乌头原碱通过减少细胞内K+外流和破坏NLRP3炎性体的组装，缓解NLRP3炎性体相关疾病。

背景：BMA（Benzoylmesaconine）是从传统中药乌头（Aconitum carmichaeli Debx）中提取的一种主要生物碱，具有强大的抗炎特性。目的：本研究旨在探讨 BMA 对 NLRP3 炎性体的抑制机制，并评估其对 NLRP3 相关代谢性疾病的疗效：方法：建立了一个经典的NLRP3炎性体激活骨髓源性巨噬细胞（BMDM）模型，以评估BMA对NLRP3上下游蛋白表达以及热蛋白沉积的影响。利用两种不同的动物疾病模型，即 MSU 诱导的痛风性关节炎和 DSS 诱导的结肠炎，来验证 BMA 在体内的抗炎活性：体外研究结果表明，BMA 可通过抑制白细胞介素-1β（IL-1β）的分泌和 GSDMD-N 蛋白的表达来抑制 NLRP3 炎性体的激活。这一机制涉及阻断细胞内 K+ 外流和干扰 NLRP3 炎性体的形成。体内研究表明，BMA 能明显减轻 MSU 诱导的急性痛风和 DSS 诱导的结肠炎模型的炎症症状：这些研究结果表明，BMA 可通过双重机制有效抑制 NLRP3 信号通路的激活：减少细胞内 K+ 外流和破坏 NLRP3 炎性体的组装。这种多方面的作用凸显了 BMA 治疗 NLRP3 相关疾病的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.