Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 10/2011; 52(1):182-90. DOI: 10.1016/j.freeradbiomed.2011.10.444
Source: PubMed


Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for 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 arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the 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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    • "Interestingly, LPS-induced inflammatory signals are known to mediate activation of NF-țB through ROS [31]. It has recently been shown that various antioxidants, such as vitamin C and vitamin E, inhibit ROS-induced inflammatory responses by preventing activation of NF-țB [32]. "
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    • "Thus, it blocks several hyperglycemiainduced pathways, one of them being endogenous AGE and dicarbonyls formation [16]. But benfotiamine has also antioxidant properties [17] [18], protects endothelial cells under conditions of hyperglycemia [19] in vitro and in animal models, modulates the activity of the nitric oxide synthase [20] [21] (NOS, a critical enzyme that promotes nitric oxide generation), has anti-inflammatory effects [22], and protects against smoke induced endothelial dysfunction in rats [23]. Moreover, we and others [24] have previously shown protective effects of benfotiamine or thiamine on endothelial cells in humans postprandially or during hyperglycemia [25]. "
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