Endothelial SIRT-1 has a critical role in the maintenance of capillarization in brown adipose tissue.

Brown adipose tissue (BAT) has critical roles in thermogenesis and systemic metabolism. Capillary rarefaction was reported to develop in BAT with dietary obesity, and previous studies showed that suppression of vascular endothelial growth factor A (VEGF-A) reduced capillary density in BAT, promoting the functional decline of this organ. Capillarization is regulated through the balance between angiogenesis and vasculogenesis on the one hand and apoptosis of endothelial cells (ECs) on the other; however, the role of EC apoptosis in BAT remained to be explored. In studies testing the role of boysenberry polyphenols (BoyP) in BAT, we found that BoyP decreased EC apoptosis, enhanced capillarization in BAT, and ameliorated dietary BAT dysfunction, which was associated with the upregulation of nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin 1 (SIRT-1) in ECs. Our studies suggest that EC SIRT-1 would be one of the potential targets of BoyP that contributes to BAT capillarization and function.

Boysenberry polyphenol inhibits endothelial dysfunction and improves vascular health.

Endothelial cells have an important role in maintaining vascular homeostasis. Age-related disorders (including obesity, diabetes, and hypertension) or aging per se induce endothelial dysfunction that predisposes to the development of atherosclerosis. Polyphenols have been reported to suppress age-related endothelial cell disorders, but their role in vascular function is yet to be determined. We investigated the influence of boysenberry polyphenol on vascular health under metabolic stress in a murine model of dietary obesity. We found that administration of boysenberry polyphenol suppressed production of reactive oxygen species (ROS) and increased production of nitric oxide (NO) in the aorta. It has been reported that p53 induces cellular senescence and has a crucial role in age-related disorders, including heart failure and diabetes. Administration of boysenberry polyphenol significantly reduced the endothelial p53 level in the aorta and ameliorated endothelial cell dysfunction in iliac arteries under metabolic stress. Boysenberry polyphenol also reduced ROS and p53 levels in cultured human umbilical vein endothelial cells (HUVECs), while increasing NO production. Uncoupled endothelial nitric oxide synthase (eNOS monomer) is known to promote ROS production. We found that boysenberry polyphenol reduced eNOS monomer levels both in vivo and in vitro, along with an increase of eNOS dimerization. To investigate the components of boysenberry polyphenol mediating these favorable biological effects, we extracted the anthocyanin fractions. We found that anthocyanins contributed to suppression of ROS and p53, in association with increased NO production and eNOS dimerization. In an ex vivo study, anthocyanins promoted relaxation of iliac arteries from mice with dietary obesity. These findings indicate that boysenberry polyphenol and anthocyanins, a major component of this polyphenol, inhibit endothelial dysfunction and contribute to maintenance of vascular homeostasis.

Effects of acute and chronic boysenberry intake on blood pressure and endothelial function in spontaneous hypertensive rats.

The effects of acute or chronic intake of boysenberry juice or artificial vinegar on blood pressure (BP) and endothelial function were investigated in spontaneous hypertensive rats (SHR). A single administration of boysenberry juice (BJ, equivalent to 0.5 mL/kg body weight) or artificial boysenberry juice vinegar (BJV, equivalent to 0.5 mL BJ and 0.10 g acetic acid/kg body weight) decreased both systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly. Reductions in SBP of the control group compared with the BJ and BJV groups reached maxima of -16.8±4.3 and -28.4±7.3 mmHg 8 h after administration, respectively. Chronic SBP- and DBP-lowering effects were also observed upon daily feedings of both BJ and BJV at 4 wk. No significant differences were found in SBP or DBP between respective acute and chronic intake of BJ and BJV, except for the decrease in DBP after 4 wk of BJV intake. This suggests that the polyphenol constituents in BJ and BJV likely play a major role in lowering SBP and DBP under these conditions and that acetic acid added to BJ exerts a DBP-lowering effect after 4 wk of BJV intake. The polyphenolic constituents of these beverages might elevate plasma NO concentration via aortic endothelial nitric oxide synthase activation, but the effects of chronic intake on blood pressure might also be at least partly mediated by the renin-angiotensin system. These results may help explain the beneficial effects of boysenberry intake on cardiovascular health, such as reduced blood pressure and improved endothelial function.

Acute and chronic flow-mediated dilation and blood pressure responses to daily intake of boysenberry juice: a preliminary study.

There is an increasing interest in dietary polyphenols for risk reduction in cardiovascular diseases. The aim of this study was to evaluate acute and chronic flow-mediated dilation (FMD) and blood pressure responses to daily intake of boysenberry juice. FMD of the brachial artery was measured in six subjects in the initial, intermediate and follow-up stages of a 4-week open-label intervention study. The intake of boysenberry juice (180 ml/d) increased FMD with progression of intervention stage, and FMD differed in the follow-up stage compared with pre-intake baseline (p = 0.0163 < 0.0167 = 0.1/6) using Bonferroni correction. Changes in systolic blood pressure (SBP) correlated negatively with SBP before intake only in the follow-up stage (r = -0.961 and p = 0.0007 at 3.5 h), indicating a greater SBP reduction in subjects with higher SBP. These results suggest that daily intake of boysenberry juice is beneficial for reducing cardiovascular risk.

Antihypertensive effect of boysenberry seed polyphenols on spontaneously hypertensive rats and identification of orally absorbable proanthocyanidins with vasorelaxant activity.

The antihypertensive effect of a single oral administration of a boysenberry seed polyphenol extract to spontaneously hypertensive rats was evaluated at different doses (100 and 200 mg/kg), and a significant decrease in systolic blood pressure (SBP) was observed up to 6 h post administration. The extract was separated into proanthocyanidin-rich and ellagitannin fractions by solvent partition. A significant decrease in SBP was observed only after administering the proanthocyanidin-rich fraction, and this decrease was abolished by an N(G)-nitro-L-arginine methyl ester (L-NAME) injection. An analysis of the orally absorbable components showed that intact dimeric and trimeric procyanidins and propelargonidins were detectable in the plasma with a maximal concentration 2 h post administration. The vasorelaxant activity of the extract was also confirmed by in vitro assay using rat aorta rings. These results suggest that proanthocyanidins (PAs) in boysenberry seeds may have played an important role in the observed antihypertensive effect.

Identification and quantification of short oligomeric proanthocyanidins and other polyphenols in boysenberry seeds and juice.

Proanthocyanidins and other polyphenols in the seeds and juice of boysenberry were quantitatively analyzed. Polyphenolic extracts were prepared from the waste seeds and commercial juice by chromatographic fractionation. Compositional analysis revealed that both extracts contained six polyphenolic classes: flavanol monomers, proanthocyanidins, anthocyanins, ellagic acid, ellagitannins, and flavonol glycosides. Ellagitannins were the most abundant polyphenols in both extracts. Proanthocyanidins were present as short oligomers consisting of dimeric and trimeric procyanidins and propelargonidins, with the most abundant component being procyanidin B4 in both extracts. Quantification by high-performance liquid chromatography-mass spectrometry (HPLC-MS) revealed that the seeds contained a 72-fold higher amount of proanthocyanidins than the juice. These results indicate that boysenberry fruits contain short oligomeric proanthocyanidins along with flavanol monomers and the seeds represent a good source of short oligomeric proanthocyanidins.

Evolving lipid vesicles in prebiotic hydrothermal environments.

We compared three different kinds of lipid vesicles made of saturated fatty acids, unsaturated fatty acids, and phospholipids for their evolutionary capabilities in a simulated hydrothermal environment. Encapsulation of the glycine monomers enhanced the oligomerization of peptides in all cases. Fatty acid vesicles remained stable at higher temperatures and efficiently utilized heat energy for this synthetic reaction. Phospholipid vesicles were destabilized by higher temperatures, and thus were found to be better suited to enhance synthetic reactions at lower temperatures.