Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK/NF-κB pathway
Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK/NF-κB pathway
复制标题
DOI：
10.1016/j.fct.2019.110583
复制
发表时间：
2019-09-01
影响因子：
4.3
通讯作者：
Lee, Sang Han
中科院分区：
文献类型：
--
作者：
Alam, Md Badrul;Ju, Mi-Kyoung;Lee, Sang Han
我们研究了protopine（PTP）的抗炎活性，并试图确定其在LPS刺激的BV 2细胞和角叉菜胶（CA）诱导的小鼠模型中的作用机制。PTP（5、10和20 μ M）处理以浓度依赖性方式显著抑制NO和PGE（2）的分泌，但通过下调LPS诱导的BV 2细胞中iNOS和考克斯-2的表达而不影响细胞活力。PTP还减弱促炎趋化因子（如MCP-1）和细胞因子（包括TNF-α、IL-1 β和IL-6）的产生，并增强抗炎细胞因子IL-10的表达。此外，PTP通过抑制I κ B的降解和下调包括p38、ERK 1/2和JNK蛋白在内的丝裂原活化蛋白激酶（MAPK）的表达来抑制NF-κ B的核转位。此外，与未处理小鼠相比，PTP处理显著抑制CA诱导的小鼠爪水肿。在CA诱导的小鼠中，PTP（50 mg/kg）处理也消除了iNOS和考克斯-2蛋白的表达。PTP处理还消除了I κ B磷酸化，其阻碍了NF-κ B的活化。总的来说，这些结果表明PTP具有通过调节MAPK/NF-κ B信号级联来减轻CA和LPS诱导的炎症症状的潜力。
We investigated the anti-inflammatory activity of protopine (PTP) and sought to determine its mechanism of action in LPS-stimulated BV2 cells and a carrageenan (CA)-induced mouse model. Treatment with PTP (5, 10, and 20 mu M) significantly suppresses the secretion of NO and PGE(2) in a concentration-dependent manner without affecting cell viability by downregulating iNOS and COX-2 expression in LPS-induced BV2 cells. PTP also attenuates the production of pro-inflammatory chemokines, such as MCP-1, and cytokines, including TNF-alpha, IL-1 beta and IL-6, and augments the expression of the anti-inflammatory cytokine IL-10. In addition, PTP suppresses the nuclear translocation of NF-kappa B by hindering the degradation of I kappa B and downregulating the expression of mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK protein. Furthermore, PTP treatment significantly suppresses CA-induced paw oedema in mice compared to that seen in untreated mice. Expression of iNOS and COX-2 proteins is also abrogated by PTP (50 mg/kg) treatment in CA-induced mice. PTP treatment also abolishes I kappa B phosphorylation, which hinders the activation of NF-kappa B. Collectively, these results suggest PTP has potential for attenuating CA- and LPS-induced inflammatory symptoms through modulation of MAPKs/NF-kappa B signaling cascades.