School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; National and Local United Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, Shenyang Pharmaceutical University, Shenyang, China.
J Ethnopharmacol. 2018 May 10;217:205-211. doi: 10.1016/j.jep.2018.02.027. Epub 2018 Feb 21.
Huo Luo Xiao Ling Dan (HLXLD), a traditional Chinese medicine (TCM), is commonly used for the treatment of rheumatoid arthritis (RA).
To explore the potential therapeutic mechanism of HLXLD on anti-inflammatory activity.
A metabolomic approach based on UFLC-MS/MS to profile arachidonic acid (AA) metabolic changes was used. The cyclooxygenase (COX) and lipoxygenase (LOX) catalyzed metabolites in plasma were quantified on 7, 14, 21, and 28 days after the rats injected with Complete Freund's adjuvant and orally administrated with HLXLD, methotrexate and dexamethasone in parallel as the positive control drugs.
Nineteen metabolites involved in COX and LOX pathways in RA model group were significant increased compared with normal group (P < 0.05), including 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, 8-HETE, leukotriene B(LTB), prostaglandin E (PGE), PGI, PGD, PGF, thromboxane B (TXB), etc. From day 7 to day 28, the trajectory direction of HLXLD group and positive control groups gradually moved towards the initial space, and the concentrations of AA and its metabolites after HLXLD treatment were significantly reduced in dual pathways compared to control groups.
HLXLD induced a substantial change in the AA metabolic profiles through refrain the expression of COX and LOX. The present investigation also highlights that distinct ingredients of this formula tend to inhibit different target to achieve a therapeutic effect.
活洛消癥灵丹（HLXLD），一种中药（TCM），常用于治疗类风湿关节炎（RA）。
探索 HLXLD 抗炎活性的潜在治疗机制。
采用基于 UFLC-MS/MS 的代谢组学方法，对花生四烯酸（AA）代谢变化进行分析。在大鼠注射完全弗氏佐剂后，平行给予 HLXLD、甲氨蝶呤和地塞米松作为阳性对照药物，分别于第 7、14、21 和 28 天，对 COX 和 LOX 催化的血浆代谢物进行定量。
与正常组相比，RA 模型组中 COX 和 LOX 途径中的 19 种代谢物显著增加（P<0.05），包括 12-羟基二十碳四烯酸（12-HETE）、15-HETE、8-HETE、白三烯 B（LTB）、前列腺素 E（PGE）、PGI、PGD、PGF、血栓素 B（TXB）等。从第 7 天到第 28 天，HLXLD 组和阳性对照组的轨迹方向逐渐向初始空间移动，HLXLD 治疗后 AA 及其代谢物的浓度在双途径中明显低于对照组。
HLXLD 通过抑制 COX 和 LOX 的表达，对 AA 代谢谱产生显著影响。本研究还表明，该配方的不同成分倾向于抑制不同的靶点来达到治疗效果。
