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Abstract: Tilianin has been shown to down-regulate TNF-α induced expression of vascular cell adhesion molecules in endothelial cells. In this study, we examined the anti-atherogenic effects and molecular mechanism of tilianin in vitro and in vivo. Male low-density lipoprotein receptor null mice (Ldlr−/−) fed a high cholesterol diet showed significant increases in the size of atherosclerotic lesions, as well as increased plasma levels of total cholesterol, triglycerides, and the pro-inflammatory cytokines TNF-α and IL-1β, when compared with Ldlr−/− mice fed a normal diet. Mice fed the high cholesterol diet supplemented with tilianin showed significantly reduced lesion sizes and reductions in cytokine levels, without significant changes in serum cholesterol levels. Primary cultured peritoneal macrophages from Ldlr−/− mice showed increased level of TNF-α andIL-1β mRNA in response to treatment with lipopolysaccharide; these increases were inhibited by co-treatment with tilianin. Moreover, tilianin inhibited NF-κB activation, as determined by electrophoretic mobility shift and NF-κB promoter assays. Upstream of NF-κB activation, tilianin inhibited IκB kinase activation and the subsequent phosphorylation and degradation of IκBα protein. These results suggest that tilianin ameliorates atherosclerosis by inhibiting the production of the NF-κB-dependent pro-inflammatory cytokines, TNF-α and IL-1β, via the inhibition of IκB kinase activity. [Copyright &y& Elsevier]

Abstract: Orexigenic neuropeptides NPY and AgRP play major roles in feeding and are closely related to obesity and diabetic metabolic syndrome. This study explored the inhibitory effect of rutecarpine on feeding and obesity in high-fat-diet-induced (C57BL/6) and leptin-deficient (ob/ob) obese mice. Both mice strains developed obesity, but the obesity was inhibited by the reduced food intake resulting from rutecarpine treatment (0.01%, p <0.01). Blood cholesterol, non-fasting glucose, insulin, and leptin levels were reduced, compared with the control group. Rutecarpine inhibited the expression of NPY and AgRP in the arcuate nucleus (ARC) of the hypothalamus and suppressed the expression of both neuropeptides in N29-4 neuronal cells. These results indicate that rutecarpine ameliorates obesity by inhibiting food intake, which involves inhibited expression of the orexigenic neuropeptides NPY and AgRP. [Copyright &y& Elsevier]