Cordyceps mycelia的多醣體萃取物CME-1抑制巨噬細胞iNOS表現之機轉探討

發炎反應 (Inflammation)是指組織遭受外界刺激導致自體免疫反應之生理現象，主要在控制感染和促進組織的修復，然而過度的發炎反應卻會造成體內免疫系統、血管、器官等的損害；因此，減緩發炎反應所造成的身體損傷便成為新藥開發的準則之一。過去文獻顯示中草藥冬蟲夏草 (Cordyceps sinensis)具有抗氧化、抗發炎、抑制腫瘤生長、調節免疫反應等功效；其有效成分CME-1亦被證實具有對抗過氧化氫所誘發之活性氧自由基生成、粒線體膜電位下降及細胞死亡之功能。本篇論文將探討CME-1之抗發炎功效及其作用機轉。本研究使用脂多醣體 (LPS)誘發RAW264.7巨噬細胞中發炎因子inducible nitric oxide synthase (iNOS)的表現；實驗結果發現CME-1可濃度相關性地抑制LPS所誘發的iNOS表現，且其作用機轉可能經由抑制IκB-α的降解、及p65、Akt、ERK、JNK、p38之磷酸化，與減少ROS的生成而來。進一步探討上述訊息傳遞因子之上游調控蛋白Protein Phosphatases 2A (PP2A)是否參與CME-1之抗發炎機轉中；發現事先給予PP2A的抑制劑okadaic acid會明顯弱化CME-1對發炎因子iNOS及其作用機轉的抑制作用。本篇論文發現CME-1可有效抑制LPS誘發的RAW264.7細胞之iNOS表現，且其作用機轉可能是經由調控PP2A訊息傳遞路徑而來。此研究結果顯示CME-1具有治療發炎相關疾病，如：阿茲海默症、巴金森症、動脈硬化症、類風濕性關節炎等之潛力。

關鍵字

冬蟲夏草菌絲體；抗發炎；脂多醣體；自由基

並列摘要

Inflammation of macrophage is activated upon appropriate extracellular stimulation, most often by stress or pro-inflammatory cytokines, and lipopolysaccharide (LPS). The mitogen-activated protein kinase (MAPK) signaling pathway in macrophage is one of the most extensively investigated intracellular signaling cascades involved in LPS-induced pro-inflammatory responses. Thus, inhibition of the production of these inflammatory mediators in activated macrophage may prevent or suppress a variety of inflammatory diseases, including atherosclerosis, sepsis, and endotoxemia. CME-1, a novel water-soluble polysaccharide fraction, isolated from Cordyceps sinensis (a precious Chinese herb) mycelia. Except a study has been reported that CME-1 protects RAW264.7 cells against oxidative damage via inhibition of sphingomyelinases activity and reduction of C16- and C18-ceramide levels, no reports are available about the inhibitory mechanism of CME-1 on LPS-induced inflammatory insult in macrophages. Therefore, the results of this study revealed that CME-1 inhibited LPS-induced expressions of nitric oxide (NO) production and induced nitric oxide synthase (iNOS) and IκB-α degradation in RAW264.7 cells. On the other hand, CME-1 suppressed p65, Akt, ERK, JNK, and p38 protein phosphorylation and inhibited the formation of ROS in RAW264.7 cells. The important finding of this study is that okadaic acid, a specific and potent inhibitor of protein phosphatases 2A, restored CME-1’s inhibitory effects on iNOS production, IκB-α degradation and the phosphorylations of p65, Akt, ERK, JNK, and p38 proteins. Taken together, the data generated from this study it can be suggested that CME-1 may be of therapeutic value used as a potent anti-inflammatory agent.

並列關鍵字

CME-1 ； RAW264.7 ； LPS ； iNOS ； ROS

參考文獻

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Cordyceps mycelia的多醣體萃取物CME-1抑制巨噬細胞iNOS表現之機轉探討

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