Corydecumine G Inhibits Microglia Activation via MAPK Pathway in a Rat Model of Neuropathic Pain
Corydecumine G Inhibits Microglia Activation via MAPK Pathway in a Rat Model of Neuropathic Pain
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Corydecumine G 在神经性疼痛大鼠模型中通过 MAPK 通路抑制小胶质细胞激活
DOI：
10.1016/j.jchemneu.2022.102124
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
Fang Zhao
中科院分区：
文献类型：
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作者：
Liaoxi Tan;Yixin Hu;Xinyi Zhang;Chunlei Zhang;Chuchu Xi;Zhao Yang;Zhengyu Cao;Fang Zhao
小胶质细胞活化通过产生与神经元相互作用以增强神经元过度兴奋的多种促炎性细胞因子在神经病理性疼痛的发作和进展中起重要作用。Cordyceridescumbens（Thunb.）人，一种传统的中药在临床上用于治疗轻度癌症疼痛、痴呆和缓解脑缺血。苯酞异喹啉类化合物是C.已显示，伏香豆及其衍生物之一Corydecumine G（Cor G）抑制神经元兴奋性。本研究旨在探讨Cor G对神经病理性疼痛大鼠模型的镇痛效果、Cor G对小胶质细胞活化的影响及其可能的机制。Cor G浓度依赖性地减轻CCI大鼠的机械痛和热痛敏，抑制CCI诱导的p38/ERK磷酸化和脊髓小胶质细胞活化，降低CCI大鼠L4-L 6脊髓背角NO、inos、TNF-α、Pge 2的表达水平。30 μM Cor G预处理可抑制LPS诱导的BV 2小胶质细胞活化，这种作用通过inos、Tnf-α、IL-1β、IL-6和磷酸化p38/ERK途径实现，提示Cor G可能具有治疗神经病理性疼痛的作用。
Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms.Neuropathic pain was modeled using chronic constriction sciatic nerve injury (CCI) in rats. Western blot, immunofluorescence, and qRT-PCR were used to evaluate the levels of protein and mRNA.Intraperitoneal administration of Cor G concentration-dependently ameliorates mechanical and thermo allodynia, suppresses CCI-induced p38/ERK phosphorylation and spinal cord microglia activation, and attenuates the expression levels of NO, inos, Tnf-α, Pge2 in dorsal horn of L4-L6 spinal cord on the ligation side in CCI rats. Pretreatment with 30 μM Cor G decreased LPS-induced BV2 microglia activation, which occurred via the inos, Tnf-α, Il-1β, Il-6 and phospho-p38/ERK pathways.Taken together, we suggest that Cor G, the specific phthalide isoquinoline from traditional Chinese medicine Corydalis Decumbentis Rhizoma, may be promising for treatment of neuropathic pain.