Antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract and underlying mechanisms
Antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract and underlying mechanisms
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DOI：
10.1016/j.biopha.2019.109753
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Xu, Xueqing
中科院分区：
文献类型：
--
作者：
Nguyen, Tienthanh;Chen, Xin;Xu, Xueqing
美洲大蠊是一种常见的中药材，几百年来一直用于治疗关节炎、发热、疼痛、四肢发炎。然而，文献中几乎没有科学数据支持其使用。本研究旨在评价美洲大蠊提取物（Periplaneta americana extract，PAE）的解热、抗炎和镇痛作用，并探讨其作用机制。采用内毒素致热法、角叉菜胶致足肿胀法、热板法、扭体法和福尔马林法观察其解热、抗炎和镇痛作用。通过抗氧化活性分析、炎性细胞因子表达和发热介质测定以及通路活化分析来探讨其作用机制。超高效液相色谱-高分辨质谱分析结果表明，提取物中含有多巴胺、香豆素、二肽、维生素、有机酸、氨基酸及其代谢产物等有机化合物。PAE在体外以剂量依赖性方式显示抗氧化活性，并降低RAW 264.7细胞中NO、IL-1 β、IL-6和TNF-α的蛋白质产生和mRNA表达。PAE能显著抑制福尔马林致小鼠扭体反应和舔体时间，延长热板反应潜伏期，减轻角叉菜胶所致小鼠足肿胀和炎症反应，降低LPS所致大鼠rT升高，并呈剂量依赖性。此外，PAE还能显著抑制热大鼠血浆NO、IL-6、IL-1 β、TNF-α、PGE（2）和cAMP水平的升高，显著抑制热大鼠炎症反应途径的激活，抑制热大鼠足爪MDA、GSH含量、MPO、SOD活性和FRAP含量的变化。总之，研究结果表明，PAE通过减少内源性炎症介质的产生和阻断MAPK/NF-κ B信号通路而产生潜在的抗伤害、抗炎和解热作用，这支持了其传统用于治疗各种疾病的说法。
Periplaneta americana is a common traditional Chinese medicinal material which has been used to treat arthritis, fever, aches, pains, and inflammation of the extremities for several hundred years. However, little scientific data exists in literature to support its use. The purpose of this study was to evaluate the antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract (PAE) and explore its underlying mechanism. The antipyretic, anti-inflammatory and analgesic activities were evaluated by LPS-induced fever, carrageenan-induced paw edema, abdominal writhing, hot plate and formalin tests, respectively. The mechanism of action was explored by antioxidant activity analysis, inflammatory cytokines expression and febrile mediator measurement, and pathway activation analysis. The results from UHPLC-HRMS indicated that the extract was found to contain dopamine, coumarin, dipeptide, vitamin, organic acid, amino acid and its metabolites, and other organic compounds. PAE showed in a dose-dependent manner antioxidant activity and reduced the protein production and mRNA expression of NO, IL-1 beta, IL-6, and TNF-alpha in RAW 264.7 cells in vitro. Moreover, PAE significantly and dose-dependently inhibited the writhing responses and licking time in formalin tests, increased response latency in the hot plate test, reduced carrageenan-induced paw edema and inflammation in mice, decreased LPS-induced rT increase in rats. Furthermore, PAE treatment markedly inhibited the increase in the levels of NO, IL-6, IL-1 beta, TNF-alpha, PGE(2) and cAMP in plasma of fevered rat, greatly suppressed the activation of inflammatory response pathway and the change of MDA and GSH concentration, MPO and SOD activity as well as FRAP capacity in paw induced by carrageenan injection. In conclusion, the findings suggested that PAE produced potential antinociceptive, anti-inflammatory and antipyretic effects by reducing production of endogenous inflammatory mediators and blocking the MAPK/NF-kappa B signaling pathway which support the claim for its traditional use in the treatment of various diseases.