Epiisopiloturine 是一种来自 Pilocarpus microphyllus 的生物碱，通过干扰小胶质细胞中的 TLR4/NF-κB-MAPK 信号通路来减轻 LPS 诱导的神经炎症,Oxidative Medicine and Cellular Longevity

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Epiisopiloturine 是一种来自 Pilocarpus microphyllus 的生物碱，通过干扰小胶质细胞中的 TLR4/NF-κB-MAPK 信号通路来减轻 LPS 诱导的神经炎症
Oxidative Medicine and Cellular Longevity Pub Date : 2023-4-28 , DOI: 10.1155/2023/4752502
João Antônio Costa de Sousa ₁ , Francisco Vinícius Clemente Serra Azul ₁ , Ana Bruna de Araújo ₁ , Rebeca Colares Tomé ₁ , Francisca Raysse Mesquita Silva ₁ , Silvânia Maria Mendes de Vasconcelos ₂ , Francisco José Rios ₃ , Luzia Kalyne Almeida Moreira Leal ₁

Affiliation

神经炎症存在于影响中枢神经系统（CNS）的多种疾病的病理生理机制中。小胶质细胞在启动和维持炎症过程中发挥着重要作用。表异毛果碱 (EPI) 是一种咪唑生物碱，是从毛果芸香碱(jaborandi)中提取的毛果芸香碱的副产品，具有良好的抗炎和镇痛特性。在本研究中，我们研究了 EPI 对脂多糖 (LPS) 诱导的小胶质细胞 (BV-2 细胞) 炎症反应的影响，并探索了假定的潜在分子机制。通过 LDH 活性和 MTT 测试评估，细胞活力不受 EPI (1-100 μg /mL) 的影响。EPI（25、50 和 100 μg /mL）预处理显着降低了 LPS 诱导的促炎反应，如亚硝酸盐产生和 iNOS 蛋白表达减少所观察到的。EPI (25 μg /mL) 使 IL-6 和 TNF- α 的产生分别减少 40% 和 34%。然而，抗炎 IL-10 的产生没有观察到变化。从机制上讲，EPI抑制LPS诱导的TLR4表达以及NF-κB p65和MAPKs（JNK和ERK1/2）的磷酸化，但在LPS刺激的细胞中未观察到TREM2受体表达的变化。总之，我们的数据证明了 EPI 在小胶质细胞中的有效抗炎特性。这些效应与 TLR4 表达的减少和细胞内信号级联的抑制有关，包括 NF- κ B 和 MAPK（JNK 和 ERK1/2）。

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Epiisopiloturine, an Alkaloid from Pilocarpus microphyllus, Attenuates LPS-Induced Neuroinflammation by Interfering in the TLR4/NF-κB-MAPK Signaling Pathway in Microglial Cells

Neuroinflammation is present in the pathophysiological mechanisms of several diseases that affect the central nervous system (CNS). Microglia have a prominent role in initiating and sustaining the inflammatory process. Epiisopiloturine (EPI) is an imidazole alkaloid obtained as a by-product of pilocarpine extracted from Pilocarpus microphyllus (jaborandi) and has shown promising anti-inflammatory and antinociceptive properties. In the present study, we investigated the effects of EPI on the inflammatory response in microglial cells (BV-2 cells) induced by lipopolysaccharide (LPS) and explored putative underlying molecular mechanisms. Cell viability was not affected by EPI (1-100 μg/mL) as assessed by both LDH activity and the MTT test. Pretreatment with EPI (25, 50, and 100 μg/mL) significantly reduced the proinflammatory response induced by LPS, as observed by a decrease in nitrite oxide production and iNOS protein expression. EPI (25 μg/mL) reduced IL-6 and TNF-α production, by 40% and 34%, respectively. However, no changes were observed in the anti-inflammatory IL-10 production. Mechanistically, EPI inhibited the TLR4 expression and phosphorylation of NF-κB p65 and MAPKs (JNK and ERK1/2) induced by LPS, but no changes were observed in TREM2 receptor expression in LPS-stimulated cells. In conclusion, our data demonstrated the potent anti-inflammatory properties of EPI in microglial cells. These effects are associated with the reduction of TLR4 expression and inhibition of intracellular signaling cascades, including NF-κB and MAPKs (JNK and ERK1/2).

更新日期：2023-04-29

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