Six new studies point to red raspberry's potential anti-inflammatory properties
Explore further: Controlling inflammation to reducechronic disease risk
More information: Kirakosvan, A., et al. Cardioprotective Effects of Red Raspberries in Obesity-prone Rats . The FASEB Journal , April 2016,vol. 30, no. 1
The intake of red raspberry fruit is inversely related to cardiac risk factors and cardiovascular disease. In this study, the effect of red raspberry intake was assessed in obesity-prone, Zucker Fatty rats as a model of cardiometabolic risk. For 8 weeks, rats were fed a higher-fat diet (45% of kcal) containing 2% (wt/wt) freeze-dried whole raspberry powder (RSP) or added sugars (CON) to match macronutrient and calorie content. RSP reduced fasting triglycerides and fasting glucose but did not appear to affect fasting insulin, fasting low-density lipoprotein, or body weight gain. RSP trended but did not significantly reduce systolic blood pressure, but did significantly reduce heart rate relative to time-matched CON rats. Noteworthy, compared to CON, RSP significantly reduced left ventricular (LV) enlargement and wall thickening as measured by echocardiography, without impacting ejection fraction. LV remodeling is a known risk factor for and precursor to heart failure. Ongoing studies of LV tissue will reveal molecular changes related to inflammation and fibrosis. Red raspberries could be an excellent candidate for dietary management cardiometabolic risk, including risk for Type-2 diabetes. Also, intake of red raspberries could reduce eventual pathologies like heart failure, which in the US, is the leading diagnosis over the age of 65.
Shay, N.F., et al. Intakeof Whole Raspberries and the Raspberry Phytochemicals, Ellagic Acid andRaspberry Ketone Reduces Adiposity, Improves Glucose Control and Changes Hepatic Gene Expression Profiles in High-fat Fed Mice . The FASEB Journal , April 2016,vol. 30 no. 1
The commonly-available red raspberry, Rubus strigosis , is a relatively understudied nutrient-dense fruit with both high phytochemical and fiber content. We tested the hypothesis that intake of whole raspberry food products and/or raspberry phytochemicals would remediate metabolic problems in C57BL/6J male mice fed a high-fat, high-sucrose diet modeling the obesigenic Western diet (HF).
Groups of mice (n=8) were provided either low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF plus Raspberry Juice Concentrate (HF+RJC), HF plus Raspberry Puree Concentrate (HF+RPC), HF plus Raspberry Freeze-Dried Powder (HF+RFP), HF plus Ellagic Acid (HF+EA), HF plus Raspberry Ketone (HF+RK), or HF plus a combination of EA and RK (HF+E+R) for 10 weeks. Fruit products were provided at 10% of total energy and phytochemicals at ~ 0.2% (w/w) of diet. Animals were fed experimental diets ad libitum; body weight and food intake was recorded weekly. In week nine, a glucose tolerance test was conducted; after ten weeks, animals were killed, serum collected, and liver tissue saved for RNA isolation and gene expression analysis. Glucose tolerance testing indicated that Area Under the Curve (AUC) was generally improved with raspberry supplements vs. HF diet consumption; intake of RFP and E+R produced AUCs essentially equivalent to LF-fed mice.
Weight gain was ameliorated in several groups compared to HF-fed mice. Intake of HF+RJC, HF+RPC, and HF+E+R significantly reduced weight gain during the study. Food efficiency generally paralleled weight gain.
Finally, a custom gene array was used to evaluate the expression of 87 different genes related to various aspects of metabolism, membrane transport, inflammation, and gene transcription factors. The effects of RJC, RPC, EA, or RK intake were evaluated with this focused array system (Qiagen) and Ingenuity Pathway Analysis software (Qiagen). Intake of raspberry foods and pure phytochemicals exerted positive effects on gene expression in the liver. Analysis of relative mRNA levels revealed that these foods and phytochemicals differentially regulated gene expression in multiple cellular pathways associated with the lipid, carbohydrate, and xenobiotic metabolism, antioxidant effect, and inflammation. The HF+RK diet differentially regulated 30 genes, the HF+EA diet 21 genes, the HF+RJC diet 31 genes, and the HF+RPC diet 33 genes, compared with HF diet (P < 0.01–0.1). Interestingly, the consumption of these raspberry products altered the relative mRNA levels so that the pattern of expression more closely resembled that of the mice fed a LF diet rather than the HF-fed mice. We conclude that although many biological mechanisms may be responsible, clearly, hepatic gene expression is being altered in a favorable manner with the consumption of raspberries and raspberry phytochemicals. Our results allow for the identification of candidate mechanisms by which raspberry phytochemicals may act in metabolic syndrome.
Zhu, M.J., et al. Dietary raspberries ameliorate metabolic syndromes in diet-induced obese mice . The FASEB Journal , April 2016vol. 30 no. 1
Introduction Obesity affects more than one third of the US population, which predisposes to a number of serious diseases. The typical “Western diet” is mainly blamed for the current obesity epidemics. Thus, optimizing the diet composition will be one of the primary approaches to prevent obesity. Raspberry contains very high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects, and also their likely effects to prevent obesity.
Objective This study was to evaluate beneficial effects of raspberry supplementation on adiposity, glucose and lipid homeostasis impaired due to diet-induced obesity.
Methods Wild-type male Mice (six weeks old) were randomized into 4 groups receiving a control or typical western diet (HFD) supplemented with or without 5% freeze dried raspberry for 12 weeks, when mice were sacrificed for tissue collection.
Results Feed intake was not different among dietary groups. HFD feeding dramatically increased body weight, which can be alleviated by raspberry supplementation towards to the end of feeding trail. In addition, baseline blood glucose is significantly elevated in HFD group, which were reduced by raspberry supplementation. Addition of raspberry improved glucose tolerance and insulin sensitivity impaired by westernized HFD, and has a tendency to reduce adiposity elicited by HFD. In addition, Dietary Raspberry reduced abundance of lipid droplets in the liver of HFD mice as indicated by Oil-Red-O staining and has a tendency to decrease serum triglyceride level in HFD mice.
Conclusion Dietary raspberry supplementation reduced adiposity and improved glucose and lipid homeostasis impaired by diet-induced obesity.
Noratto, G., et al. Effectsof Raspberry Dietary Supplementation on Risk Biomarkers of Diabetes Related Complications and Heart Disease in Diabetic Mice . The FASEB Journal , April 2016,vol. 30 no. 1
We investigated the effects of raspberry consumption on diabetes-related complications and heart disease in obese diabetic mice. Mice (4–5 wk old) were fed either AIN-93G (control) or AIN-93G supplemented with freeze-dried raspberries (9.75%) (isocaloric) for 8 wk. At the end of the study, blood and heart tissues were collected and analyzed using standard analytical protocols.
Raspberry intake, at dose equivalent to 208 g freeze dried raspberry/day for a 60-kg human adult; protected against appetite loss, weight loss and cachexia observed in the control group. However, levels of lipid peroxidation, pro-atherogenic molecules, and endotoxins in plasma were similar between groups. Plasma adipokine resistin, a hormone signaling molecule correlated with hyperinsulinemia/hyperglycemia, was higher in raspberry group (1777 vs 1165 ρg/mL, p < 0.05). Controversially, no differences were found in plasma insulin concentrations; whereas fasting glucose tended (p = 0.08) to be lower in the raspberry group (688 vs 759 mg/dL). This suggests that higher concentrations of plasma resistin in the raspberry group is correlated with higher body weight and is consistent with its delayed cachexia. Heart tissue disease biomarkers leptin, resistin, total cholesterol, triglycerides, and oxidized lipids were similar between experimental groups. However; plasminogen activator inhibitor-1 (PAI-1) tended to be lower in the raspberry compared to the control group (1124 vs 1234 ρg/mg protein) (p > 0.05). PAI-1 has been linked to decreased oxidative stress and interleukin-6 in blood.
These findings demonstrate that raspberry consumption helps to decrease cachexia and may decrease cardiac fibrosis in diabetes at an advanced age. Future studies are needed to prove the clinical relevance of raspberry consumption.
Sasaki, G., et al., Ellagic Acid and Quercetin are High-Affinity Ligands of Human PeroxisomeProliferator-Activated Receptor Alpha in an In-Vitro Competitive Binding Assay . The FASEB Journal , April 2016,vol. 30 no. 1
Introduction Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition characterized by fat accumulation in the liver, and can be a precursor to more severe liver diseases, such as Non-Alcoholic Steatohepatitis, cirrhosis and liver cancer. Currently, there is no accepted therapy for NAFLD, except for diet and exercise, which is difficult to administer successfully to often obese individuals diagnosed with NAFLD.
Objective The objective was to measure the potential for a set of select phytochemicals to serve as ligands for human peroxisome proliferator-activated receptor-alpha (hPPARα), a member of the nuclear hormone receptor (NHR) superfamily. PPARα is a key regulator factor controlling intracellular lipid oxidation in tissues including liver and muscle.
Methods A time-resolved fluorescence resonance energy transfer (TR-FRET) competitive binding assay was used, with hPPARα as the ligand binding domain (ThermoFisher). The compounds tested consisted of two positive controls: GW 9662 and fenofibric acid and the phytochemicals tested were daidzein, ellagic acid, genistein, quercetin, and raspberry ketone. Compounds were tested across a range of concentrations. Binding affinity to the human PPARα receptor was measured by detecting the fluorescent emission at 520 nm and 495 nm; competition curves and an IC 50 values were determined for each of the compounds.
Results The tested compounds demonstrated a wide range of binding affinities. Positive controls had IC 50 values consistent with their accepted values: GW9662 = 332 nM and Fenofibric acid =@ 48 μM. For the phytochemicals, ellagic acid and quercetin showed the greatest affinities with IC 50 values of 269 nM and 1.3 μM, respectively. The other phytochemicals did not bind to the PPARα receptor as well: genistein = 241 μM, daidzein = 4.3 M, and raspberry ketone = 19 mM.
Conculsions The identification of ellagic acid and quercetin as compounds with relatively high affinity for PPARα was unexpected, and to our knowledge, not previously reported. Their binding affinities were in close to that of the high-affinity compound, GW9662, and in fact, ellagic acid had greater affinity for PPARα than GW9662. Both of these phytochemicals had higher affinity to PPARα than fenofibric acid, the pharmacologically active metabolite of fenofibrate. Despite a lower affinity, this compound produces significant metabolic effects in humans, administered as a drug with the trade name Tricor. Although ellagic acid may not be absorbed to a significant degree, its downstream metabolites, the urolithins, have similar structure to ellagic acid and quercetin, and the potential for urolithins to be agonists of PPARα remains to be tested. Quercetin, on the other hand, is absorbed into the blood stream in the small intestine and thus could interact subsequently with the liver and/or other tissues such as the muscle.
To our knowledge, this work is the first to demonstrate direct ligand binding of phytochemicals to the human PPARα NHR and suggests some natural compounds may have the potential to enhance fatty acid oxidation by transactivation of the PPARα pathway.
Thomas, A., et al. Inhibitory Effects of Red Raspberry Polyphenols on Osteoclastogenesis in RANKL-Stimulated RAW264.7 Murine Macrophages . The FASEB Journal , April 2016, vol. 30 no. 1
Osteoclasts and osteoblasts regulate skeletal mass, structure, and strength via their respective roles in resorbing and forming bone. Osteoclasts, the cells associated with breakdown of bone, are stimulated by a cytokine known as RANKL (receptor activator of nuclear factor κB ligand), a member of the tumor necrosis factor (TNF) superfamily. Polyphenols such as flavonoids found in plant-derived foods have demonstrated anti-inflammatory effects in various tissues. Red raspberries are a rich source of such polyphenolic compounds. Using mouse macrophage cells (RAW 264.7), we examined whether red raspberry polyphenols (RRP) could inhibit the proliferation and activity of RANKL-induced osteoclastic cells in a dose-dependent manner. Tartrate resistant acid phosphatase (TRAP) activity and staining of TRAP positive multinucleated osteoclasts, used as indicators of osteoclast differentiation and activity, decreased in a dose dependent manner with RRP treatment. Although, nitrite concentrations were not influenced by RRP treatment, there was a reduction in interleukin (IL)-1β and IL-6 with RPP demonstrating its anti-inflammatory role in bone cells. Western blot analyses showed a dose-dependent reduction in expression of inducible nitric oxide synthase (iNOS) protein and bone morphogenetic protein-2 (BMP-2) by RRP indicating that the polyphenols act to retrain the RANKL mediated osteoclastogenesis. Overall, these findings suggest that the polyphenols associated with red raspberry would inhibit the negative effects of osteoclasts on bone health. Further investigation is warranted to elucidate the molecular mechanisms by which RRP affect osteoclastogenesis.
虽然仅有非常初步的证据支持鞣花酸对人体的益处，但鞣花酸已被作为一种防癌，防心脏病及其他疾病的保健品进行销售。所以 美国食品药品监督管理局（FDA） 已将其确定为“消费者应该规避的假癌症药物” [10] 。 许多美国保健品销售商已收到美国食品药品监督管理局的警告信，称推广鞣花酸违反《联邦食品、药品及化妆品法》（ Federal Food, Drug, and Cosmetic Act ） [11][12]。FDA的提示其为了维护消费者的合法权利，并不意味着是对鞣花酸防癌，防心脏病及其他疾病研究结果的否定。自然界有许多药食同源的材料，食用天然产物，要比使用某种活性成分的补充剂可能更为安全些。