Excess vascular oxidative stress has been linked to impaired endothelium-dependent arterial relaxation in hypercholesterolemia. ␣ -Tocopherol (AT) preserves endothelial function in hypercholesterolemia although the mechanism(s) for this protective effect is (are) not known. We examined the tissue-specific effects of AT on oxidized LDL (ox-LDL)-mediated endothelial dysfunction in male New Zealand White rabbits. Animals consumed chow deficient in ( Ͻ 10 IU/kg) or supplemented with (1,000 IU/kg) AT for 28 d. Exposure of thoracic aortae from AT-deficient animals to ox-LDL (0-500 g/ml) for 4 h produced dose-dependent inhibition of acetylcholine-mediated relaxation ( P Ͻ 0.05) while vessels derived from animals consuming AT were resistant to ox-LDL-mediated endothelial dysfunction. Animals consuming AT demonstrated a 100-fold increase in vascular AT content and this was strongly correlated with vessel resistance to endothelial dysfunction from ox-LDL ( R ϭ 0.67; P ϭ 0.0014). These results were not explained by an effect of AT on ox-LDL-mediated cytotoxicity by LDH assay or scanning electron microscopy. Vascular incorporation of AT did produce resistance to endothelial dysfunction from protein kinase C stimulation, an event that has been implicated in the vascular response to ox-LDL. Human aortic endothelial cells loaded with AT also demonstrated resistance to protein kinase C stimulation by both phorbol ester and ox-LDL. Thus, these data indicate that enrichment of vascular tissue with AT protects the vascular endothelium from ox-LDL-mediated dysfunction, at least in part, through the inhibition of protein kinase C stimulation. These findings suggest one potential mechanism for the observed beneficial effect of AT in preventing the clinical expression of coronary artery disease that is distinct from the antioxidant protection of LDL. ( J. Clin. Invest. 1996. 98: 386-394)

Increasing dietary AGEs intake might enrich circulating AGE level and contribute to oxidative and inflammatory progression under diabetic condition. The circulating 8-isoprostane, IL-1α and MCP-1 levels and SOD activity might be appropriate biomarkers used to evaluate dietary AGEs-associated oxidative and inflammatory stress.

These findings support the suggestion that pepino aqueous extract could attenuate the progression of diabetes via its antioxidative, anti-inflammatory and antiglycative effects.

The flavonoid fraction was extracted from the leaves of Abutilon theophrasti Medic., which are usually used as a traditional Chinese herbal medicine for the treatment of inflammation and joint pain. The current study focused on the extraction process, component analysis, and in vitro antioxidant, antibacterial, and anti-inflammatory activities of the flavonoid fraction as a part of ongoing research on bioactive substances from natural plant sources. This study evaluated the antioxidant activities via assays of DPPH radical scavenging capacity, ABTS radical scavenging capacity, and reducing power and investigated inhibitory activities against Escherichia coli, Salmonella, Staphylococcus aureus, and Streptococcus. Moreover, the inflammatory activity of the flavonoid fraction was estimated by measurement of the content of tumor necrosis factor alpha, interleukin-1-beta, interleukin-6, interleukin-10, nitric oxide, and cyclooxygenase-2 and the gene expression levels of several inflammation markers, such as inducible nitric oxide synthase and cyclooxygenase-2, in RAW 264.7 macrophages after LPS treatment. In addition, the underlying anti-inflammatory mechanisms, that is, the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, were also revealed from the gene and protein expression levels. Taken together, these results suggested that the flavonoid fraction might exert in vitro antioxidant, antibacterial, and anti-inflammatory effects on LPS-stimulated RAW 264.7 macrophages and will be potentially useful as an adjuvant treatment for oxidative stress and bacterial and inflammatory diseases.

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