{"title":"阿克替因通过抑制TLR4/MyD88/NF-κB和NLRP3/Caspase-1/GSDMD信号通路,缓解特应性皮炎的炎症和脓毒症。","authors":"Jingmin Li, Xuefei Du, Zhenzhen Mu, Xiuping Han","doi":"10.2147/JIR.S484919","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD.</p><p><strong>Methods: </strong>AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ.</p><p><strong>Results: </strong>ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade.</p><p><strong>Conclusion: </strong>ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"8009-8026"},"PeriodicalIF":4.2000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539860/pdf/","citationCount":"0","resultStr":"{\"title\":\"Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.\",\"authors\":\"Jingmin Li, Xuefei Du, Zhenzhen Mu, Xiuping Han\",\"doi\":\"10.2147/JIR.S484919\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD.</p><p><strong>Methods: </strong>AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ.</p><p><strong>Results: </strong>ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade.</p><p><strong>Conclusion: </strong>ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.</p>\",\"PeriodicalId\":16107,\"journal\":{\"name\":\"Journal of Inflammation Research\",\"volume\":\"17 \",\"pages\":\"8009-8026\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539860/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inflammation Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/JIR.S484919\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S484919","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:特应性皮炎(AD)是一种全球流行的皮肤病。免疫反应在特应性皮炎的发病机制中起着至关重要的作用。苦木素(ARC)是一种天然木质素,因其具有抗炎、抗氧化和抗癌特性而受到广泛研究。然而,ARC对AD的影响仍不确定。因此,本研究调查了 ARC 对 AD 的治疗效果:方法:用 2,4-二硝基氯苯(DNCB)诱导小鼠发生 AD 样病变。方法:用 2,4-二硝基氯苯(DNCB)诱导小鼠产生 AD 样皮损,通过测量皮损评分和厚度、病理观察和血清 IgE 浓度来评估 ARC 对 AD 的疗效。还评估了小鼠背部皮肤中相关蛋白质和基因的表达。此外,在 TNF-α 和 IFN-γ 刺激的 HaCaT 细胞中评估了 TLR4/MyD88/NF-κB 和 NLRP3/Caspase-1/GSDMD 信号通路:结果:ARC能有效缓解DNCB诱导的小鼠AD样皮炎,减少皮肤厚度、皮肤组织中肥大细胞浸润和血清总IgE水平。此外,IL-1β的表达以及TSLP和IFN-γ的mRNA转录均被下调。ARC 还抑制了 TLR4/MyD88/NF-κB 通路,分子对接证实 ARC 与 TLR4 具有特殊的结合特性。此外,ARC还通过抑制类点头受体蛋白-3/Caspase-1/GSDMD级联的激活来改善脓毒症:结论:ARC通过TLR4/MyD88/NF-κB和NLRP3/Caspase-1/GSDMD信号通路抑制炎症和脓毒症,具有显著的抗AD作用。这表明 ARC 有潜力成为治疗 AD 的候选新药,为 AD 的临床治疗提供了一种新方法。
Arctiin Alleviates Atopic Dermatitis Against Inflammation and Pyroptosis Through Suppressing TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD Signaling Pathways.
Purpose: Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD.
Methods: AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ.
Results: ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade.
Conclusion: ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.
期刊介绍:
An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.