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黄连解毒汤通过抑制脂氧合酶通路中的一氧化氮生成和类二十烷酸生物合成发挥其抗炎作用。

Huang-Lian-Jie-Du-Tang exerts anti-inflammatory effects in rats through inhibition of nitric oxide production and eicosanoid biosynthesis via the lipoxygenase pathway.

机构信息

Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, PR China.

出版信息

J Pharm Pharmacol. 2009 Dec;61(12):1699-707. doi: 10.1211/jpp/61.12.0016.

Abstract

OBJECTIVES

Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine with a long history of anti-inflammatory use, but its pharmacological effects have not been thoroughly investigated. This study aimed to evaluate the anti-inflammatory activity of HLJDT in vivo and in vitro.

METHODS

The carrageenan rat air pouch model was used to investigate the anti-inflammatory action of HLJDT after oral administration. Moreover, we exploited a modified method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to assay the effects of HLJDT on arachidonic acid metabolites.

KEY FINDINGS

Our data demonstrate that oral administration of HLJDT significantly inhibited the inflammatory responses in carrageenan-injected rat air pouches, and also significantly reduced the production of nitric oxide (NO) and leukotriene B(4) (LTB(4)) in vivo, without any influence on biosynthesis of cyclooxygenase (COX)-derived eicosanoids. Similar behaviour of HLJDT was also observed by using calcium ionophore A23187-stimulated peritoneal macrophages, where HLJDT markedly inhibited eicosanoids derived from different lipoxygenases. The NO production and the mRNA expression of inducible nitric oxide synthase (iNOS) and chemotactic factors (CCL3, CCL4, CCL5 and CXCL2) were also inhibited by HLJDT in RAW 264.7 macrophages stimulated by lipopolysaccharide.

CONCLUSIONS

Our data revealed, for the first time, that HLJDT could inhibit biosynthesis of eicosanoids derived from different lipoxygenases. Also, HLJDT may exert its anti-inflammatory effects by its suppression on eicosanoid generation, NO production and gene transcription of chemotactic factors, which supports its effectiveness in the treatment of inflammatory diseases.

摘要

目的

黄连解毒汤(HLJDT)是一种具有悠久抗炎应用历史的中药,但它的药理作用尚未得到彻底研究。本研究旨在评估 HLJDT 在体内和体外的抗炎活性。

方法

采用角叉菜胶大鼠气囊模型研究 HLJDT 口服后的抗炎作用。此外,我们利用基于液相色谱-串联质谱(LC-MS/MS)技术的改良方法来检测 HLJDT 对花生四烯酸代谢物的影响。

主要发现

我们的数据表明,HLJDT 口服给药可显著抑制角叉菜胶注射大鼠气囊中的炎症反应,还可显著降低体内一氧化氮(NO)和白三烯 B4(LTB4)的产生,而对环氧化酶(COX)衍生的类二十烷酸的生物合成没有影响。在钙离子载体 A23187 刺激的腹腔巨噬细胞中,HLJDT 也表现出类似的行为,可显著抑制不同脂氧合酶衍生的类二十烷酸。HLJDT 还可抑制脂多糖刺激的 RAW 264.7 巨噬细胞中 NO 的产生以及诱导型一氧化氮合酶(iNOS)和趋化因子(CCL3、CCL4、CCL5 和 CXCL2)的 mRNA 表达。

结论

本研究首次揭示,HLJDT 可抑制不同脂氧合酶衍生的类二十烷酸的生物合成。此外,HLJDT 可能通过抑制类二十烷酸生成、NO 产生和趋化因子基因转录来发挥其抗炎作用,这支持其在治疗炎症性疾病方面的有效性。

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