Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.
Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.
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DOI：
10.1016/j.freeradbiomed.2011.10.444
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发表时间：
2012-01-01
影响因子：
7.4
通讯作者：
Ramana, Kota V.
中科院分区：
文献类型：
--
作者：
Shoeb, Mohammad;Ramana, Kota V.
Benfotiamine 是维生素 B1 的脂溶性类似物，是一种有效的抗氧化剂，可用作治疗糖尿病并发症的食品补充剂。我们最近的研究表明苯磷硫胺在预防细菌内毒素、脂多糖 (LPS) 诱导的细胞毒性和小鼠巨噬细胞炎症反应方面具有新作用。然而，目前尚不清楚苯磷硫胺如何介导抗炎作用。在本研究中，我们研究了苯磷硫胺在调节 RAW 264.7 巨噬细胞中花生四烯酸 (AA) 途径产生的炎症脂质介质中的抗炎作用。 Benfotiamine 可阻止 LPS 诱导的 cPLA2 激活和巨噬细胞中 AA 代谢物的释放，例如白三烯 (LTB4)、前列腺素 E2 (PGE2)、血栓素 2 (TXB2) 和前列环素 (PGI2)。此外，苯磷硫胺显着阻断 LPS 诱导的 AA 代谢酶（例如 COX-2、LOX-5、TXB 合酶和 PGI2 合酶）的表达。此外，苯磷硫胺还可阻止 LPS 诱导的 ERK1/2 磷酸化以及转录因子 NF-kB 和 Egr-1 的表达。 Benfotiamine 还可以防止 LPS 诱导的氧化应激和蛋白质-HNE 加合物的形成。最重要的是，与特定的 COX-2 和 LOX-5 抑制剂相比，苯磷硫胺显着阻止 LPS 诱导的巨噬细胞死亡和单核细胞与内皮细胞的粘附。因此，我们的研究表明，AA 代谢中 COX 和 LOX 途径的双重调节可能是苯磷硫胺发挥其潜在抗炎反应的新机制。
Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response.
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影响因子：
8
作者：
Beltramo, E;Berrone, E;Porta, M
通讯作者：
Porta, M
DOI：
10.1024/0300-9831.70.6.311
发表时间：
2000-12-01
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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