a Department of Pharmacology, College of Pharmacy , Chengdu University of TCM , Chengdu , PR China.
b Sichuan College of Traditional Chinese Medicine , Mianyang , PR China.
Immunopharmacol Immunotoxicol. 2019 Jun;41(3):420-427. doi: 10.1080/08923973.2019.1588292. Epub 2019 May 28.
Pulegone, a key compound in Schizonepeta essential oil, has been identified as an anti-inflammatory. However, its underlying molecular mechanisms on NLR family pyrin domain containing 3 (NLRP3) inflammasome have not been elucidated. Here, the modulatory effects of pulegone on NLRP3 inflammasome were investigated. The C57BL/6J mice were randomly divided into five groups: Normal, Lipopolysaccharides (LPS), Dexamethasone (DEX, 5 mg/kg), Pulegone (0.095 and 0.190 g/kg) groups. All mice were challenged by LPS except for the Normal group. A reduced expression of Interleukin-18 (IL-18), Interleukin-1β (IL-1β), Interleukin-5 (IL-5), Tumor necrosis factor-α (TNF-α), Interferon-gamma (IFN-γ), Monocyte chemoattratctant protein-1 (MCP-1), Macrophage inflammatory protein-1β (MIP-1β), Monocyte colony stimulating factor (M-CSF) and Granulocyte-macrophage colony stimulating factor (GM-CSF) in serum were detected in the pulegone groups as compared to the LPS group. In addition, a reduced mRNA and protein expression production of ASC, NLRP3, and Caspase-1 were detected in lungs after pulegone administration. Histological analysis results indicated that the histological changes of lungs caused by LPS were ameliorated by pulegone. Immunohistochemical study showed a decreased positive cell numbers of P2X7R in Pulegone (0.095 and 0.190 g/kg) groups. Pulegone exerts anti-inflammatory effects on LPS-induced sepsis mice via inhibition of the NLRP3 expression.
蓬蒿脑是荆芥挥发油的主要成分之一,具有抗炎作用。但其对NLR 家族pyrin 结构域包含蛋白 3(NLRP3)炎症小体的作用机制尚未阐明。本研究旨在探讨蓬蒿脑对 NLRP3 炎症小体的调控作用。将 C57BL/6J 小鼠随机分为五组:正常组、脂多糖(LPS)组、地塞米松(DEX,5mg/kg)组、蓬蒿脑(0.095 和 0.190g/kg)组。除正常组外,其余各组均用 LPS 处理。与 LPS 组相比,蓬蒿脑组小鼠血清中白细胞介素-18(IL-18)、白细胞介素-1β(IL-1β)、白细胞介素-5(IL-5)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1β(MIP-1β)、单核细胞集落刺激因子(M-CSF)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的表达降低。此外,蓬蒿脑组小鼠肺组织中 ASC、NLRP3 和 Caspase-1 的 mRNA 和蛋白表达降低。组织学分析结果表明,蓬蒿脑可改善 LPS 引起的肺组织损伤。免疫组化结果显示,蓬蒿脑(0.095 和 0.190g/kg)组 P2X7R 阳性细胞数减少。蓬蒿脑通过抑制 NLRP3 表达对 LPS 诱导的脓毒症小鼠发挥抗炎作用。