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从 Mojabanchromanol 中分离出来,通过抑制 TLR2/4/7-MAPK 信号通路在 MLE-12 细胞中减轻颗粒物诱导的炎症反应。

Mojabanchromanol Isolated from Attenuates Particulate Matter Induced Inflammatory Responses via Suppressing TLR2/4/7-MAPK Signaling in MLE-12 Cells.

机构信息

Department of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea.

Department of Food Bioengineering, Jeju National University, 102 JeJudaehakno, Jeju 63243, Korea.

出版信息

Mar Drugs. 2020 Jul 8;18(7):355. doi: 10.3390/md18070355.

Abstract

Chromanols from marine algae are studied for drug development due to its prominent bioactive properties, and mojabanchromanol (MC), a chromanol isolated from a brown algae , is found to possess anti-oxidant potential. In this study, we hypothesized MC may attenuate particulate matter (PM)-induced and reactive oxygen species (ROS)-mediated inflammatory responses in airways and tried to identify its potential and underlying mechanism against PM (majority <2.5 µm in diameter)-induced inflammatory responses in a lung type II alveolar epithelial cell line, MLE-12. MC attenuated PM-induced malondialdehyde (MDA), a lipid peroxidation end product, and 8-hydroxydeoxyguanosine (8-OHdG), the most representative DNA oxidative damage product, further validating MC's potential in attenuating PM-induced oxidative stress. MC also suppressed PM-triggered TLR2/4/7 activation in MLE-12 cells. Moreover, MC reduced ROS-mediated phosphorylation of mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun NH (2)-terminal kinase (JNK) that were also activated in PM exposed cells. MC further inhibited the secretion of pro-inflammatory cytokines (IL-6, IL-1β and IL-33) in MLE-12 cells exposed to PM. These results provide a clear evidence for MC's potential in attenuating PM-triggered inflammatory responses in MLE-12 cells via repressing TLR2/4/7 and MAPK signaling. Therefore, MC can be developed as a therapeutic agent against PM induced airway inflammatory responses.

摘要

海洋藻类中的色满醇因其显著的生物活性而被研究用于药物开发,从褐藻中分离出的莫哈巴chromanol(MC)被发现具有抗氧化潜力。在这项研究中,我们假设 MC 可能会减轻颗粒物(PM)诱导的和活性氧(ROS)介导的气道炎症反应,并试图确定其对 PM(直径大部分小于 2.5 µm)诱导的炎症反应的潜在机制和潜在机制在肺 II 型肺泡上皮细胞系 MLE-12 中。MC 减轻了 PM 诱导的丙二醛(MDA),一种脂质过氧化终产物,和 8-羟基脱氧鸟苷(8-OHdG),最具代表性的 DNA 氧化损伤产物,进一步证实了 MC 减轻 PM 诱导的氧化应激的潜力。MC 还抑制了 MLE-12 细胞中 TLR2/4/7 的 PM 触发激活。此外,MC 降低了 ROS 介导的丝裂原活化蛋白激酶(MAPK)细胞外信号调节激酶 1/2(Erk1/2)和 c-Jun NH(2)-末端激酶(JNK)的磷酸化,这些激酶在暴露于 PM 的细胞中也被激活。MC 进一步抑制了 PM 暴露的 MLE-12 细胞中促炎细胞因子(IL-6、IL-1β和 IL-33)的分泌。这些结果为 MC 通过抑制 TLR2/4/7 和 MAPK 信号通路减轻 MLE-12 细胞中 PM 触发的炎症反应的潜力提供了明确的证据。因此,MC 可以开发为治疗 PM 诱导的气道炎症反应的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2170/7401275/5e71b464b42c/marinedrugs-18-00355-g001.jpg

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