Raspberry Ketones Research Articles

Site-directed mutagenesis enhances the activity of benzylidene acetone synthase of polyketide synthase from Polygonum cuspidatum

Polygonum cuspidatum polyketide synthase 1 (PcPKS1) has the catalytic activity of chalcone synthase (CHS) and benzylidene acetone synthase (BAS), which can catalyze the production of polyketides naringenin chalcone and benzylidene acetone, and then catalyze the synthesis of flavonoids or benzylidene acetone. In this study, three amino acid sites (Thr133, Ser134, Ser33) that may affect the function of PcPKS1 were identified by analyzing the sequences of PcPKS1, the BAS from Rheum palmatum and the CHS from Arabidopsis thaliana, as well as the conformation of the catalytic site of the enzyme. Molecular modification of PcPKS1 was carried out by site-directed mutagenesis, and two mutants were successfully obtained. The in vitro enzymatic reactions were carried out, and the differences in activity were detected by high performance liquid chromatography (HPLC). Finally, mutants T133LS134A and S339V with bifunctional activity were obtained. In addition to bifunctional activities of BAS and CHS, the modified PcPKS1 had much higher BAS activity than that of the wild type PcPKS1 under the conditions of pH 7.0 and pH 9.0, respectively. It provides a theoretical basis for future use of PcPKS1 in genetic engineering to regulate the biosynthesis of flavonoids and raspberry ketones.

The signatures of liver metabolomics and gut microbiota in high-fat diet fed mice supplemented with rhododendrol.

As aromatic compounds found within red fruits and berries, raspberry ketones (RK) have the potential for nonalcoholic fatty liver disease (NAFLD) amelioration. However, the mechanism of RK on NAFLD is unclear, and their bioactive metabolite is unknown. As the major metabolites of RK that are mainly distributed in the liver, rhododendrol (RHO) is used in our current study to test whether RHO accounts for the beneficial effect of RK on NAFLD and the underlying mechanism. In a 16-week trial, RHO significantly decreased final body weight, improved serum lipid profile and ameliorated liver inflammation. Moreover, RHO changed the gut microbiota composition, including lean phenotype-related genera, such as Bacteroides, Bilophila, Oscillibacter, Lachnospiraceae_bacterium_28_4 and Bacteroides sartorii. Liver metabolomics analysis indicated that RHO enhanced the abundance of metabolites related to alanine, aspartate, and glutamate metabolism, as well as arginine and proline metabolism. Spearman correlation analysis revealed that these metabolites were positively correlated with the gut genera enriched by RHO. Here, our findings suggested that the metabolic effects of RK might be partially attributed to its metabolite-RHO, and mice supplemented with RHO have dramatically altered hepatic metabolisms concurrent with shifts in specific gut bacteria.

Overexpression of a fusion protein of 4-coumaroyl-CoA ligase and polyketide synthase for raspberry ketone production in Chlamydomonas reinhardtii

Raspberry ketones have important therapeutic properties such as anti-influenza and prevention of diabetes. In order to obtain raspberry ketone from Chlamydomonas reinhardtii, two enzymes catalyzing the last two steps of raspberry ketone synthesis, i.e. 4-coumaryl-CoA ligase (4CL) and polyketide synthase (PKS1), were fused using a glycine-serine-glycine (GSG) tripeptide linker to construct an expression vector pChla-4CL-PKS1. The fusion gene 4CL-PKS1 driven by a PSAD promoter was transformed into a wild-type (CC125) and a cell wall-deficient C. reinhardtii (CC425) by electroporation. The results showed the recombinant C. reinhardtii strain CC125 and CC425 with 4CL-PKS1 produced raspberry ketone at a level of 6.7 μg/g (fresh weight) and 5.9 μg/g (fresh weight), respectively, both were higher than that of the native raspberry ketone producing plants (2-4 μg/g).

Raspberry Ketones Attenuate Cyclophosphamide-Induced Pulmonary Toxicity in Mice through Inhibition of Oxidative Stress and NF-ΚB Pathway.

Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP. Mice were allocated into six groups: (1) control group; (2) CP group: received a single intraperitoneal dose of CP (150 mg/kg, i.p.); and (3–6) mice were pre-treated orally with different doses of RKs (25, 50, 100, and 200 mg/kg) for 14 consecutive days, respectively, before the administration of an intraperitoneal dose of CP (150 mg/kg, i.p.). Mice were then sacrificed under anesthesia, then lungs were removed for histopathological and biochemical investigations. A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates. Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of membranes, thickening of inter alveolar septa, and proliferation of type II pneumocytes. The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen (PCNA) staining reactivity of the nuclei of the lining epithelium of the bronchioles and alveoli. CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway. However, pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity.

An optimized dose of raspberry ketones controls hyperlipidemia and insulin resistance in male obese rats: Effect on adipose tissue expression of adipocytokines and Aquaporin 7

Obesity constitutes a major worldwide problem in which hyperlipidemia and insulin resistance represents adverse metabolic consequences of it. The present study was conducted to elucidate the role of raspberry ketones (RKs) in controlling body weight gain, hyperlipidemia and insulin resistance in male obese rats through affecting the expression of various adipocytokines. As Aquaporin-7 is co-related with the expression of various adipocytokines and has recently emerged as a modulator of adipocyte metabolism, the present study evaluated the effect of RKs on adipose tissue expression of aquaporin-7(AQP7) in high-fat (HF) diet-fed rats. Groups of male rats were assigned to normal, HF diet-fed control rats and RKs-treated (250 and 500 mg/kg) groups. RKs administration effectively abrogated hyperlipidemia and oxidative burden and enhanced insulin sensitivity. In addition, treatment with RKs ameliorated adipose tissue and liver indices and the reduced adipocyte diameters. Moreover, administration of the low dose of RKs ameliorated the expression of apelin and its receptor, and visfatin with upregulating adiponectin expression compared to HF diet control rats. However, both doses effectively downregulated leptin expression. It was obvious that both RKs doses revealed effectiveness in upregulating the AQP7 expression. The present data suggest the promising therapeutic role of RKs in HF diet-induced obesity that is likely attributable, at least in part, to upregulation of AQP7 expression.

New Dietary Supplements for Obesity: What We Currently Know.

Obesity and its associated cardiometabolic alterations currently are considered an epidemic; thus, their treatment is of major importance. The cornerstone for such treatment involves therapeutic lifestyle changes; however, the vast majority of cases fail and/or significant weight loss is maintained only in the short term because of lack of compliance. The popularity of dietary supplements for weight management has increased, and a wide variety of these products are available over the counter. However, the existing scientific evidence is insufficient to recommend their safe use. Hence, the purpose of this article is to review the clinical effects, proposed mechanism of action, and safety profile of some of the new dietary supplements, including white bean extract, Garcinia cambogia, bitter orange, Hoodia gordonii, forskolin, green coffee, glucomannan, β-glucans, chitosan, guar gum, and raspberry ketones.

Development of Broad-Spectrum Natural Sunscreens using Combinations of five Plant Species

Introduction: Cancer is a range of multifactorial diseases which have in common uncontrolled increase in the number of cells invading various tissues and organs. One of its leading etiological agents is sun exposure, and therefore the use of sunscreens plays an important role in cancer prevention. Objective : In this context, the aim of this study was to verify whether the selected naturally-derived raw materials (Oli-ola dry extract, Hibiscus dry extract, Raspberry ketones, Leucoanthocyanidins isolated from grapes and Resveratrol) present adequate photoprotective properties for the development of an innovative broad-spectrum sunscreen. Methods: The determination of sunscreen activity was made in vitro , and the following parameters were obtained: Sun Protection Factor (SPF), UVA Protection Factor (UVAPF), Critical Wavelength and Boots Star Rating. Results: Innovative products showed varied results (maximum SPF=46; maximum UVAPF=22), being that all of them showed to be promising for both parameters. However, the greatest protection was shown in the UVB region. Conclusion: Thus, the Oli-Ola, Hibiscus, Leucoanthocyanidins, Raspberry Ketones and Resveratrol species, grouped in a cosmetic base lotion, showed potential for the development of innovative sunscreen products. Additionally, the SPF should be confirmed in vivo . Key words: Photoprotection, Natural sunscreens, Polyphenols, Flavonoids, Broad spectrum.

The Acute Effects of Nonstimulant Over-the-Counter Dietary Herbal Supplements on Resting Metabolic Rate

ABSTRACTBackground: Weight loss supplements are widely advertised and highly sought out products. Many supplements claim to increase body fat utilization, increase resting metabolic rate (RMR), and to improve body composition by decreasing total body fat composition. Therefore, the purpose of this study was to determine the acute effect of nonstimulant herbal supplements on RMR and substrate utilization. Methods: Ten female and 16 male participants (mean age 23.7 ± 3.9 years; mean weight 79.2 ± 18.2 kg) completed a random-repeated measures crossover study. Participants completed a total of three RMRs by either ingesting a placebo (P) or one of two supplements [raspberry ketones (R) or metabolic activator blend (MAB)] 2 hours prior to testing. Results: No significant difference was found for RMR for P vs. MAB (p = .130), vs. R (p = .588), and MAB vs. R (p = .636). No significant difference was found for respiratory quotient for P vs. MAB (p = .056), vs. R (p = .149), and MAB vs. R (p = .764). No significant difference was found for substrate utilization: percent carbohydrate utilization, P vs. MAB (p = .052), P vs. R (p = .124), and MAB vs. R (p = .680); and percent fat utilization, P vs. MAB (p = .052), P vs. R (p = .120), and MAB vs. R (p = .749). Conclusions: Therefore, nonstimulant weight loss supplements may not be beneficial for weight loss, or an increase of fat utilization.

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase

In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 in vitro. We also investigated the potential herb–drug interaction via UGT1A1 inhibition by blueberry in vivo. We demonstrated that these berries had only weak inhibitory effects on the five UGTs. Bilberry and elderberry had no apparent inhibitions. Blueberry weakly inhibited UGT1A1 with an IC50 value of 62.4±4.40μg/mL and a Ki value of 53.1μg/mL. Blueberry also weakly inhibited UGT2B7 with an IC50 value of 147±11.1μg/mL. In addition, cranberry weakly inhibited UGT1A9 activity (IC50=458±49.7μg/mL) and raspberry ketones weakly inhibited UGT2B7 activity (IC50=248±28.2μg/mL). Among tested berries, blueberry showed the lowest IC50 value in the inhibition of UGT1A1 in vitro. However, the co-administration of blueberry had no effect on the pharmacokinetics of irinotecan and its active metabolite, SN-38, which was mainly eliminated via UGT1A1, in vivo. Our data suggests that these five berries are unlikely to cause clinically significant herb–drug interactions mediated via inhibition of UGT enzymes involved in drug metabolism. These findings should enable an understanding of herb–drug interactions for the safe use of popularly-consumed berries.

How America’s Flawed Supplement Law Creates the Mirage of Weight Loss Cures

Dr. Mehmet Oz, “America’s Doctor,” recently testified before Congress on why he was promoting supplements containing Garcinia cambogia, raspberry ketones, green coffee extract and other unproven ingredients as weight loss miracles. He acknowledged that “sometimes they don’t have the scientific muster to pass as fact.” In fact, there is no legal over-the-counter botanical supplement that has demonstrated clinical efficacy as a diet pill. [The only herbal treatment that can lead to modest weight loss is ephedra combined with caffeine, but this cocktail can also cause strokes, heart attacks and sudden death; hence, ephedra was banned in 2004.]

Synthesis of Raspberry and Ginger Ketones by Nickel Boride-catalyzed Hydrogenation of 4-Arylbut-3-en-2-ones

Raspberry and ginger ketones have been synthesized in good yield by the hydrogenation of the corresponding unsaturated precursors 4-(4´-hydroxyphenyl)but-3-en-2-one and 4-(4´-hydroxy-3´- methoxyphenyl)but-3-en-2-one, respectively, using a freshly prepared suspension of nickel boride in methanol as catalyst.

The Oz craze

The Oz craze

Evaluation of ingesting Dyma-Burn Xtreme, a thermogenic dietary supplement, on hemodynamic and ECG responses in healthy, young males and females

Background Ingestion of caffeine is traditionally thought to acutely elevate both blood pressure and heart rate based on the stimulatory properties that it exerts on both the central and peripheral nervous systems, and this effect is primarily dependent on the dose as well as an individual’s sensitivity to caffeine. The purpose of this study was to evaluate the safety of the ingestion of a proprietary thermogenic dietary supplement, including the ingredients caffeine, green tea extract, raspberry ketones, and L-Carnitine on ECG and hemodynamic responses.

Effects of ingesting Dyma-Burn Xtreme, a thermogenic dietary supplement on metabolic rate and subjective measures of mood state

Background Many supplements on the market today contain ingredients that claim to increase metabolism and enhance fat loss. Green tea extract and caffeine have well known thermogenic properties. The purpose of this study was to evaluate the effects of proprietary thermogenic dietary supplement Dyma-Burn Xtreme, containing a blend of ingredients including caffeine, green tea extract, raspberry ketones and L-carnitine, on resting energy expenditure and subjective measures of alertness, focus, energy, fatigue, concentration, and hunger. Methods In a double-blind, crossover design 6 male and 6 female subjects (N = 12, 22 ± 9.5 yrs, 171 ± 11.2 cm, 76.9 ± 11.2 kg, 22.7 ± 9.5), consumed either a 2 capsule serving of Dyma-Burn Xtreme (DBX) or placebo (PLC). Subjects arrived at the lab on a 12 hour fast at 8:00am and had a baseline resting energy expenditure (REE), respiratory exchange ratio (RER), and mood state questionnaire assessed. Subjects then consumed either DBX or PLC and REE and RER were assessed in a supine position for 25 minutes, and questionnaire were assessed at 1-hour (1HR), 2-hours (2HR), 3-hours (3HR), and 4-hours (4HR) post consumption. All data was analyzed utilizing a 2X5 ANOVA and one-way ANOVA’s were used in the case of a significant interaction. A Kruskal Wallis one-way analysis of variance was used for all survey data. A significance value of 0.05 was adopted throughout. Results A significant time effect and group x time interaction effect were observed among groups for changes in REE (p > 0.05). Post-hoc analyses revealed REE levels were

Natural Abundance 2H Nuclear Magnetic Resonance Study of the Origin of Raspberry Ketone

The site-specific natural abundance deuterium distribution of raspberry ketone 3 obtained through a variety of methods has been determined through (2)H NMR spectroscopy. This technique provided a means of distinguishing between "natural" raspberry ketones biogenerated from 4-hydroxybenzalacetone (2), obtained from 4-hydroxybenzaldehyde of extractive botanical origin and acetone produced by sugar fermentation by reduction using baker's yeast and other microorganisms, and other raspberry ketone samples obtained in different "non-natural" ways. Of natural origin is also a commercial sample obtained in an unspecified manner. A mechanistic interpretation has been proposed to explain the difference of site-specific deuterium content between the examined samples.