Hua Kuo-Feng, Hsu Hsien-Ta, Huang May-Shu, Chiu Hsiao-Wen, Wong Wei-Ting, Peng Chien-Hsiu, Lin Yu-Bei, Chen Ann, Wang Chien-Chun, Hsu Chung-Hua, Wu Chun-Hsien, Lin Wen-Yu, Ho Chen-Lung, Li Lan-Hui
Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
J Inflamm Res. 2024 May 29;17:3499-3513. doi: 10.2147/JIR.S454221. eCollection 2024.
The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1β, presents a target for disease management. causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in -infected macrophages.
Honokiol's impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular HO and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-HDCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of was examined through an in vitro colony-forming units assay.
Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1β, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in -infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of HO and the phosphorylation of ERK1/2 in -infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the -mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against .
Honokiol inhibits the NLRP3 inflammasome in -infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.
含吡啉结构域的NOD样受体家族3（NLRP3）炎性小体通过调节白细胞介素-1β（IL-1β）在感染性和炎性疾病中起关键作用，是疾病管理的一个靶点。淋病每年感染超过8700万人，先前的研究表明感染的巨噬细胞中NLRP3炎性小体被激活。尚无天然产物被报道可对抗这种激活。我们研究了厚朴酚（一种来自中药的酚类化合物）对感染淋病奈瑟菌的巨噬细胞中NLRP3炎性小体激活的影响。
使用酶联免疫吸附测定（ELISA）和蛋白质印迹法分析厚朴酚对促炎介质蛋白表达的影响。通过特异性荧光探针（分别为CM-HDCFDA和MitoSOX）检测细胞内过氧化氢（HO）和线粒体活性氧（ROS）的生成，并通过流式细胞术进行分析。使用特异性荧光探针（MitoTracker和DiOC(3)）评估线粒体膜完整性，并通过流式细胞术进行分析。此外，通过体外菌落形成单位测定法检测厚朴酚对淋病奈瑟菌活力的影响。
厚朴酚可有效抑制胱天蛋白酶-1、胱天蛋白酶-11和Gasdermin D（GSDMD）的激活，并减少感染淋病奈瑟菌的巨噬细胞中IL-1β、NLRP3和含胱天蛋白酶募集结构域的凋亡相关斑点样蛋白（ASC）的细胞外释放。详细研究表明，厚朴酚可降低感染淋病奈瑟菌的巨噬细胞中HO的产生和细胞外信号调节激酶1/2（ERK1/2）的磷酸化。重要的是，应激活化蛋白激酶1/2（JNK1/2）和p38以及核因子κB（NF-κB）的激活不受影响。此外，厚朴酚可减少淋病奈瑟菌介导的线粒体内活性氧的生成，维持其完整性。此外，厚朴酚可独立于NLRP3抑制淋病奈瑟菌诱导的促炎介质IL-6和诱导型一氧化氮合酶的表达。令人印象深刻的是，厚朴酚对淋病奈瑟菌表现出体外抗淋病奈瑟菌活性。
厚朴酚可抑制感染淋病奈瑟菌的巨噬细胞中的NLRP3炎性小体，作为预防和治疗淋病相关症状的活性成分具有很大的进一步开发潜力。
