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望天树甲醇提取物通过直接抑制多种激酶来抑制炎症反应。

Methanol extract of Hopea odorata suppresses inflammatory responses via the direct inhibition of multiple kinases.

机构信息

Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.

出版信息

J Ethnopharmacol. 2013 Jan 30;145(2):598-607. doi: 10.1016/j.jep.2012.11.041. Epub 2012 Dec 7.

DOI:10.1016/j.jep.2012.11.041
PMID:23220195
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Hopea odorata Roxb. (Dipterocarpaceae) is a representative Thai ethnopharmacological herbal plant used in the treatment of various inflammation-related diseases. In spite of its traditional use, systematic studies of its anti-inflammatory action have not been performed.

MATERIALS AND METHODS

The inhibitory activities of a Hopea odorata methanol extract (Ho-ME) on the production of nitric oxide (NO), tumour necrosis factor (TNF)-α, and prostaglandin E(2) (PGE(2)) in RAW264.7 cells and peritoneal macrophages were investigated. The effects of Ho-ME on the gastritis symptoms induced by HCl/EtOH and on ear oedemas induced by arachidonic acid were also examined. Furthermore, to identify the immunopharmacological targets of this extract, nuclear fractionation, a reporter gene assay, immunoprecipitation, immunoblot analysis, and a kinase assay were employed.

RESULTS

Ho-ME strongly inhibited the release of NO, PGE(2), and TNF-α in RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ho-ME also clearly suppressed the gene expression of pro-inflammatory cytokines and chemokines, such as interferon (IFN)-β, interleukin (IL)-12, and monocyte chemotactic protein-1 (MCP-1). By analysing the inhibited target molecules, Syk and Src were found to be suppressed in the inhibition of nuclear factor (NF)-κB pathway. In addition, the observed downregulation of activator protein (AP)-1 and cAMP response element-binding (CREB) was due to the direct inhibition of interleukin-1 receptor-associated kinase (IRAK)1 and IRAK4, which was also linked to the suppression of c-Jun N-terminal kinase (JNK) and p38. In agreement with the in vitro observations, this extract also ameliorated the inflammatory symptoms in EtOH/HCl-induced gastritis and arachidonic acid-induced ear oedemas in mice.

CONCLUSION

Ho-ME has potential as a functional herbal remedy targeting Syk- and Src-mediated anti-inflammatory mechanisms. Future pre-clinical studies will be needed to investigate this possibility.

摘要

民族药理学相关性

Hopea odorata Roxb.(龙脑香科)是一种有代表性的泰国民间草药植物,用于治疗各种炎症相关疾病。尽管有其传统用途,但尚未对其抗炎作用进行系统研究。

材料和方法

研究了 Hopea odorata 甲醇提取物(Ho-ME)对 RAW264.7 细胞和腹腔巨噬细胞中一氧化氮(NO)、肿瘤坏死因子(TNF)-α和前列腺素 E(2)(PGE(2))产生的抑制作用。还研究了 Ho-ME 对盐酸/乙醇诱导的胃炎症状和花生四烯酸诱导的耳部水肿的影响。此外,为了确定该提取物的免疫药理学靶点,采用了核分离、报告基因分析、免疫沉淀、免疫印迹分析和激酶分析。

结果

Ho-ME 强烈抑制脂多糖(LPS)刺激的 RAW264.7 细胞和腹腔巨噬细胞中 NO、PGE(2)和 TNF-α的释放。Ho-ME 还明显抑制了促炎细胞因子和趋化因子(如干扰素(IFN)-β、白细胞介素(IL)-12 和单核细胞趋化蛋白-1(MCP-1)的基因表达。通过分析受抑制的靶分子,发现 Syk 和 Src 在核因子(NF)-κB 途径的抑制中受到抑制。此外,观察到的激活蛋白(AP)-1 和 cAMP 反应元件结合(CREB)的下调是由于白细胞介素-1 受体相关激酶(IRAK)1 和 IRAK4 的直接抑制,这也与 c-Jun N 末端激酶(JNK)和 p38 的抑制有关。与体外观察结果一致,该提取物还改善了乙醇/盐酸诱导的胃炎和花生四烯酸诱导的耳部水肿小鼠的炎症症状。

结论

Ho-ME 作为一种针对 Syk-和Src 介导的抗炎机制的功能性草药疗法具有潜力。未来的临床前研究将需要研究这种可能性。

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