Paeonol ameliorates CFA-induced inflammatory pain by inhibiting HMGB1/TLR4/NF-κB p65 pathway
Paeonol ameliorates CFA-induced inflammatory pain by inhibiting HMGB1/TLR4/NF-κB p65 pathway
复制标题
DOI：
10.1007/s11011-020-00645-9
复制
发表时间：
2020-11-12
影响因子：
3.6
通讯作者：
Wang, Min
中科院分区：
文献类型：
--
作者：
Qiu, Chen;Yang, Liu-Di;Wang, Min
高迁移率族蛋白1（HMGB 1）介导的炎性细胞因子的释放增强导致疼痛感觉，并已涉及炎性疼痛的病因学。丹皮酚（PAE）是厚朴中的主要活性酚类成分，通过抗炎作用发挥神经保护作用。然而，PAE在炎性疼痛中的作用和机制仍有待充分阐明。在这项研究中，我们表明，PAE治疗显着改善机械和热痛觉过敏的小鼠诱导的完全弗氏佐剂（CFA）。PAE给药的镇痛作用与抑制CFA损伤后前扣带皮层（ACC）（负责疼痛处理的关键脑区）中HMGB 1以及下游信号分子（包括Toll样受体4（TLR 4）、核NF-κ B p65、TNF-α和IL-1 β）的表达增强相关。此外，HMGB 1抑制剂Gly抑制HMGB 1活性可减轻CFA诱导的疼痛，并沿着小鼠中PAE介导的镇痛作用，同时降低CFA损伤后TLR 4、NF-κ B p65、TNF-α和IL-1 β的表达。总之，我们发现PAE通过抑制HMGB 1/TLR 4/NF-κ B p65通路和ACC中细胞因子TNF-α和IL-1 β的产生来发挥镇痛作用。
The enhanced release of inflammatory cytokines mediated by high mobility group box1 (HMGB1) leads to pain sensation, and has been implicated in the etiology of inflammatory pain. Paeonol (PAE), a major active phenolic component in Cortex Moutan, provides neuroprotective efficacy via exerting anti-inflammatory effect. However, the role and mechanism of PAE in inflammatory pain remain to be fully clarified. In this study, we showed that PAE treatment significantly ameliorated mechanical and thermal hyperalgesia of mice induced by complete Freund's adjuvant (CFA). The analgesic effect of PAE administration was associated with suppressing the enhanced expression of HMGB1 as well as the downstream signaling molecules including toll-like receptor 4 (TLR4), the nuclear NF-kappa B p65, TNF-alpha and IL-1 beta after CFA insult in the anterior cingulate cortex (ACC), a key brain region responsible for pain processing. Furthermore, inhibition of HMGB1 activity by glycyrrhizin (GLY), an HMGB1 inhibitor, alleviated CFA-induced pain and also facilitated PAE-mediated analgesic effect in mice along with the decreased expression of TLR4, NF-kappa B p65, TNF-alpha and IL-1 beta upon CFA injury. Collectively, we showed PAE exerted analgesic effect through inhibiting the HMGB1/TLR4/NF-kappa B p65 pathway and subsequent generation of cytokines TNF-alpha and IL-1 beta in the ACC.