tilianin and Atherosclerosis

The huge global burden of atherosclerotic cardiovascular diseases (CVDs) represents an urgent unmet need for the development of novel therapeutics. Dracocephalum moldavica L. has been used as a traditional Uygur medicine to treat various CVDs for centuries. Tilianin is a major flavonoid component of D. moldavica L. and has potential for preventing atherosclerosis. However, the molecular mechanisms that tilianin attenuate atherosclerosis are far from fully understood.. The purpose of this study is to investigate the efficiency and underlying mechanisms of tilianin in controlling lipid profile and preventing atherogenesis.. The lipid-lowering effect of tilianin was evaluated in C57BL/6 and ApoE. Tilianin treatment improved lipid profiles in C57BL/6 and dyslipidemic ApoE. This study demonstrated the lipid-lowering effect of tilianin through SREBP2-mediated transcriptional activation of LDLR. Our findings reveal a novel anti-atherosclerotic mechanism of tilianin and underlie its potential clinical use in modulating CVDs with good availability and affordability.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Cholesterol, LDL; Flavonoids; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, LDL; RNA, Ribosomal, 16S; Transcriptional Activation; Up-Regulation

We investigated the effect of tilianin upon inducible nitric oxide synthesis in the plasma of low-density lipoprotein receptor knock-out (Ldlr-/-) mice fed with high cholesterol diet and in primary peritoneal macrophages of Ldlr-/- mice. High cholesterol diet induced nitric oxide production in the plasma of Ldlr-/- mice. Tilianin reduced the level of nitric oxide (NO) in plasma from Ldlr-/- mice induced by the high cholesterol diet. Tilianin also inhibited the NO production from the primary culture of peritoneal macrophages treated with lipopolysaccharide. The inhibition of NO production was caused by the suppression of inducible nitric oxide synthase (iNOS) gene expression in peritoneal macrophages isolated from Ldlr-/- mice. Moreover, tilianin inhibited the transcriptional activation of iNOS promoter that has NF-kappaB binding element. Thus, these results provide the first evidence that tilianin inhibit iNOS expression and production of NO and may act as a potential anti-inflammatory agent.

Topics: Animals; Atherosclerosis; Down-Regulation; Flavonoids; Glycosides; Inflammation; Male; Mice; Mice, Knockout; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Promoter Regions, Genetic; Receptors, LDL; Sinus of Valsalva; Tissue Distribution; Tyrosine