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Crataegus laevigata and Crataegus monogyna (hawthorn) were subjected to drought and cold stress treatments, and polyphenolic extracts from control and stress-treated plants were assayed for antioxidant capacities using a modified version of the Total Antioxidant Status Assay (Randox, San Francisco, CA). In addition, these plants were analyzed for levels of flavanol-type substance [(-)-epicatechin] and flavonoid (vitexin 2' '-O-rhamnoside, acetylvitexin 2' '-O-rhamnoside, and hyperoside) constituents that are important metabolites in hawthorn herbal preparations used to treat patients with heart disease. Drought and cold stress treatments caused increases in levels of (-)-epicatechin and hyperoside in both Crataegus species. Such treatments also enhanced the antioxidant capacity of the extracts. The results from this study thus indicate that these kinds of stress treatments can enhance the levels of important secondary metabolites and their total antioxidant capacities in leaves of Crataegus.

Metabolic syndrome can precede the development of type 2 diabetes and cardiovascular disease and includes phenotypes such as obesity, systemic inflammation, insulin resistance, and hyperlipidemia. A recent epidemiological study indicated that blueberry intake reduced cardiovascular mortality in humans, but the possible genetic mechanisms of this effect are unknown. Blueberries are a rich source of anthocyanins, and anthocyanins can alter the activity of peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism. The effect of blueberry intake was assessed in obesity-prone rats. Zucker Fatty and Zucker Lean rats were fed a higher-fat diet (45% of kcal) or a lower-fat diet (10% of kcal) containing 2% (wt/wt) freeze-dried whole highbush blueberry powder or added sugars to match macronutrient and calorie content. In Zucker Fatty rats fed a high-fat diet, the addition of blueberry reduced triglycerides, fasting insulin, homeostasis model index of insulin resistance, and glucose area under the curve. Blueberry intake also reduced abdominal fat mass, increased adipose and skeletal muscle PPAR activity, and affected PPAR transcripts involved in fat oxidation and glucose uptake/oxidation. In Zucker Fatty rats fed a low-fat diet, the addition of blueberry also significantly reduced liver weight, body weight, and total fat mass. Finally, Zucker Lean rats fed blueberry had higher body weight and reduced triglycerides, but all other measures were unaffected. In conclusion, whole blueberry intake reduced phenotypes of metabolic syndrome in obesity-prone rats and affected PPAR gene transcripts in adipose and muscle tissue involved in fat and glucose metabolism.

Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In ‘salt-sensitive’ HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155 to 138 mmHg, p=.02) and diastolic BP (79 to 72 mmHg, p=.04), 24-hour ambulatory systolic (130 to 123 mmHg, p=.02) and diastolic BP (67 to 62 mmHg, p=.02), and carotid-femoral pulse wave velocity (12.4 to 11.0 m/s, p=.03). Urinary F2-isoprostanes decreased by 31% (209 to 144 pmol/mmol Cr, p=.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of ‘salt-sensitive’ hypertension, a phenotype present in many HFPEF animal models, and suggest shared pathophysiological mechanisms linking these two conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.

Background Heart failure with preserved ejection fraction (HFPEF) involves failure of cardiovascular reserve in multiple domains. In HFPEF animal models, dietary sodium restriction improves ventricular and vascular stiffness and function. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular-arterial (V-A) coupling in hypertensive HFPEF. Methods and Results Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD (target sodium 50 mmol/2100 kcal) for 21 days. We measured baseline and post-DASH/SRD brachial and central BP (via radial arterial tonometry), and cardiovascular function with echocardiographic measures (all previously invasively validated). Diastolic function was quantified via the Parametrized Diastolic Filling formalism, which yields relaxation/viscoelastic (c) and passive/stiffness (k) constants through analysis of Doppler mitral inflow velocity (E-wave) contours. Effective arterial elastance (Ea) end-systolic elastance (Ees), and V-A coupling (defined as the ratio Ees:Ea) were determined using previously published techniques. Wilcoxon matched-pairs tests were used for pre-post comparisons. The DASH/SRD reduced clinic and 24-hour brachial systolic pressure (155±35 to 138±30 and 130±16 to 123±18 mmHg, both p=.02) and central end-systolic pressure trended lower (116±18 to 111±16 mmHg, p=.12). In conjunction, diastolic function improved (c, 24.3±5.3 to 22.7±8.1 s−1;p=.03; k, 252±115 to 170±37 s−1;p=.03), Ea decreased (2.0±0.4 to 1.7±0.4 mmHg/ml;p=.007), and V-A coupling improved (Ees:Ea, 1.5±0.3 to 1.7±0.4;p=.04). Conclusions In hypertensive HFPEF patients, the sodium-restricted DASH diet was associated with favorable changes in ventricular diastolic function, arterial elastance, and V-A coupling.

Obesity, systemic inflammation, and hyperlipidemia are among the components of metabolic syndrome, a spectrum of phenotypes that can precede the development of type 2 diabetes and cardiovascular disease. Animal studies show that intake of anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the activity of tissue peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism and inflammation. However, it is unknown if physiologically relevant, anthocyanin-containing whole foods confer similar effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich tart cherries was tested in the Zucker fatty rat model of obesity and metabolic syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and macronutrient-matched control diet. Tart cherry intake was associated with reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal) weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression, and plasma IL-6 and TNF-alpha. Tart cherry diet also increased retroperitoneal fat PPAR-alpha and PPAR-gamma mRNA (P = .12), decreased IL-6 and TNF-alpha mRNA, and decreased nuclear factor kappaB activity. In conclusion, in at-risk obese rats fed a high fat diet, physiologically relevant tart cherry consumption reduced several phenotypes of metabolic syndrome and reduced both systemic and local inflammation. Tart cherries may reduce the degree or trajectory of metabolic syndrome, thereby reducing risk for the development of type 2 diabetes and heart disease.

Elevated plasma lipids, glucose, insulin, and fatty liver are among components of metabolic syndrome, a phenotypic pattern that typically precedes the development of Type 2 diabetes. Animal studies show that intake of anthocyanins reduces hyperlipidemia, obesity, and atherosclerosis and that anthocyanin-rich extracts may exert these effects in association with altered activity of tissue peroxisome proliferator-activated receptors (PPARs). However, studies are lacking to test this correlation using physiologically relevant, whole food sources of anthocyanins. Tart cherries are a rich source of anthocyanins, and whole cherry fruit intake may also affect hyperlipidemia and/or affect tissue PPARs. This hypothesis was tested in the Dahl Salt-Sensitive rat having insulin resistance and hyperlipidemia. For 90 days, Dahl rats were pair-fed AIN-76a-based diets supplemented with either 1% (wt:wt) freeze-dried whole tart cherry or with 0.85% additional carbohydrate to match macronutrient and calorie provision. After 90 days, the cherry-enriched diet was associated with reduced fasting blood glucose, hyperlipidemia, hyperinsulinemia, and reduced fatty liver. The cherry diet was also associated with significantly enhanced hepatic PPAR-alpha mRNA, enhanced hepatic PPAR-alpha target acyl-coenzyme A oxidase mRNA and activity, and increased plasma antioxidant capacity. In conclusion, physiologically relevant tart cherry consumption reduced several phenotypic risk factors that are associated with risk for metabolic syndrome and Type 2 diabetes. Tart cherries may represent a whole food research model of the health effects of anthocyanin-rich foods and may possess nutraceutical value against risk factors for metabolic syndrome and its clinical sequelae.

The structure and energetics for the reaction of OH + isoprene f adduct have been examined using ab initio molecular orbital methods. The structure of each HO-isoprene adduct was optimized using Becke's threeparameter hybrid method employing the LYP correction functional (B3LYP) with the 6-31G** basis set, and using Møller-Plesset correlation energy correction truncated at second-order (MP2) with both the 6-31G** and the 6-311G** basis sets. Single-point energy calculations using fourth-order Møller-Plesset perturbation theory including single, double, triple, and quadruple excitations, as well as spin projection (PMP4(SDTQ)) with the 6-311G** basis set, were carried at these optimized geometries. The single-point energy was further corrected with zero-point energy (ZPE) to assess the stability of the OH-isoprene adducts. At the PMP4-(SDTQ)/6-311G**//MP2/6-311G** + ∆ZPE level of theory addition of OH to the 1 and 4 carbons of isoprene produces adducts which are 37.9 and 35.4 kcal mol -1 (respectively) more stable than the OH and isoprene reactants, while addition of OH to the 2 and 3 carbons results in adducts which are 25.6 and 24.2 kcal mol -1 more stable than the reactants. Experimental detection of the products from the OH + isoprene reaction using a discharge-flow system coupled with a mass spectrometer shows evidence for the production of all four possible adducts. These results suggest that each adduct is formed with nonnegligible yields, allowing each to participate in subsequent steps in the OH-initiated oxidation of isoprene.