Polyphenolics from Acai (Euterpe oleracea Mart.) and Red Muscadine Grape (Vitis rotundifolia) Protect Human Umbilical Vascular Endothelial Cells (HUVEC) from Glucose- and Lipopolysaccharide (LPS)-Induced Inflammation and Target MicroRNA-126
Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.
"    Euterpe oleraceae (Acai), a large palm tree indigenous to the Amazon River, had been evaluated for phenolic constituents and their biological activity.    Due to the structural complexity of PAC derivatives and high difficulties in their separation, studies on these compounds are limited in comparison with other polyphenols.   Usually, catechins give unresolved high-performance liquid chromatography (HPLC) peaks, due to the similarity in their structures and also to the large number of phenolic groups that can give the same interactions with chromatographic stationary phase. "
[Show abstract][Hide abstract] ABSTRACT: The ability of muscadine grape skin, seed, or combined skin and seed extracts to inhibit mouse ear inflammation, edema, and polymorphonuclear leukocyte infiltration was tested following topical application of 12-O-tetradecanoylphorbol 13-acetate (TPA). Ethanolic extracts of skins, seeds, or a combination of these from purple (Ison) cultivars were applied to both ears of female Swiss mice 30 minutes after TPA (2 microg per ear) administration. Control mice were treated with indomethacin or 50% ethanol vehicle 30 minutes after TPA. Ear thickness was measured before TPA and at 4 and 24 hours post-TPA administration to assess ear edema. Ear punch biopsies were collected at 24 hours and weighed as a second marker of edema. Myeloperoxidase (MPO) (EC 220.127.116.11) activity was measured in each ear punch biopsy as an index of neutrophil infiltration. Extracts of muscadine skin, seed, and combination treatments significantly reduced ear edema, ear biopsy weight, and MPO activity compared to TPA vehicle control. There was no significant difference in anti-inflammatory activity of the skin and seed extracts. However, an additive effect was observed with the combination treatment that was statistically similar to the anti-inflammatory activity of indomethacin treatment. It can be concluded that muscadine skin, seed, and combination skin/seed extracts exhibit significant topical anti-inflammatory properties.
[Show abstract][Hide abstract] ABSTRACT: Chronic intestinal inflammation is an established risk factor for colon cancer. Polyphenolic compounds from fruit and vegetables have been shown to have anti-inflammatory properties in several cell lines and tissues. However, their anti-inflammatory mechanisms, involving microRNAs in the regulation of inflammation, have not been extensively investigated. The goal of this research was to assess the chemopreventive potential of polyphenolics extracted from red wine made with Lenoir grapes (Vitis aestivalis hybrid) in human colon-derived CCD-18Co myofibroblasts cells, and to assess the potential involvement of microRNA-126 (miR-126) in the underlying mechanisms. The results show that the polyphenolic red wine extract (WE) decreased mRNA expression of lipopolysaccharide (LPS)-induced inflammatory mediators NF-kB, ICAM-1, VCAM-1, and PECAM-1 by 1.95-, 1.98-, 1.52-, and 1.84-fold respectively, in a dose dependent manner (0-100 μg of gallic acid equivalent (GAE) mL(-1)) down to 0.80-, 0.79-, 0.66-, and 0.68-fold in DMSO-treated control cells not challenged with LPS, respectively. Correspondingly, miR-126, which has a target region within the 3'-UTR of VCAM-1 mRNA, was increased 2.79-fold by the WE at 100 μg GAE mL(-1). The potential role of miR-126 was confirmed by transfecting cells with a specific miR-126-antagomir, as-miR-126. Transfection with as-miR-126 down-regulated miR-126 to 0.71-fold in the control cells and up-regulated mRNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 to 1.80-, 1.49-, 2.30-, and 1.95-fold of controls, respectively. WE at 100 μg GAE mL(-1) partially reversed the effects of the as-miR-126 to 1.02-, 1.01-, 1.04-, and 1.05-fold, for mRNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 respectively. This indicates the potential role of miR-126 in the anti-inflammatory properties of polyphenolics from red wine in CCD-18Co myofibroblasts cells.
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