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


RESULTS
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.
Zeng
Huawu
H
Department of Natural Product Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, PR China.
Liu
Xiaohua
X
Dou
Shengshan
S
Xu
Wen
W
Li
Na
N
Liu
Xiaojun
X
Zhang
Weidong
W
Hu
Zhenlin
Z
Liu
Runhui
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000001:Calcimycin; D002351:Carrageenan; D002460:Cell Line; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015777:Eicosanoids / Q000096:biosynthesis*; D007249:Inflammation / Q000188:drug therapy; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D008084:Lipoxygenase / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D023421:Models, Animal; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D008517:Phytotherapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018055:Receptors, Eicosanoid / Q000378:metabolism; D053719:Tandem Mass Spectrometry
D000893:Anti-Inflammatory Agents; D002630:Chemotactic Factors; D004365:Drugs, Chinese Herbal; D015777:Eicosanoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; C045607:huang-lien-chieh-tu-tang; D007975:Leukotriene B4; D009569:Nitric Oxide; D000001:Calcimycin; D002351:Carrageenan; D008084:Lipoxygenase; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases