Bergamot Polyphenolic Fraction Research Articles

Standaryzowana kompozycja polifenoli z bergamoty – czy może być opcją terapeutyczną u wybranych pacjentów z zaburzeniami lipidowymi? – analiza przypadków klinicznych

Lipid metabolic disorders are one of the most common cardiovascular risk factors. The basis for the treatment of dyslipidemia is lifestyle modification and, in selected patients – pharmacotherapy with the use of statins. In some patients, non-pharmacological treatment is not effective enough and their overall cardiovascular risk is relatively low. In such patients, there is no indication for statin therapy and functional food and dietary supplements could be the therapeutic option. One of the new and relatively well-tested dietary supplements is bergamot polyphenolic fraction (BPF). The article analyzes the results of the use of BPF in 3 patients with various stages of lipid disorders.

Nowe możliwości terapii osób z zespołem metabolicznym

The occurrence of metabolic syndrome is a risk factor for developing cardiovascular disease. Moreover, the size oflow-density lipoprotein (LDL) particles, and liver dysfunction identified as nonalcoholic fatty liver disease (NAFLD) both represent important biomarkers for the development of cardiometabolic risk in patients with metabolic syndrome. Patients being treated with bergamot polyphenolic fraction show significant reductions in fasting plasma glucose, serum LDL cholesterol and triglycerides along with an increase of high-density lipoprotein cholesterol level. This effect is accompanied in ultrasonography examination by significant reduction NAFLD.

The effect of bergamot polyphenolic fraction on lipid transfer protein system and vascular oxidative stress in a rat model of hyperlipemia

BackgroundExperimental and epidemiological studies show that bergamot polyphenolic fraction (BPF) ameliorates the serum lipemic profile, normalizes blood pressure and improves non alcoholic fatty liver disease in patients suffering from metabolic syndrome. Despite this evidence, the molecular mechanisms responsible for these beneficial effects remain unclear. The aim of our study is to clarify the effects of BPF on the lipoprotein assembly and to identify oxidative stress biomarkers correlating hyperlipidaemia and BPF-induced metabolic changes.MethodsMale Wistar rats (180–200 g) were randomly assigned to receive a standard diet, a hypercholesterolemic diet or a hypercholesterolemic diet+BPF (20 mg/Kg/rat daily, gavage), respectively, for 90 days. Total cholesterol (tChol), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and fasting plasma glucose were evaluated at the baseline as well as at the end of the treatment. To assess the effect of BPF on the Lipid Transfer Protein System, detection of ACAT, LCAT, CETP, PON1, Apo A1 and Apo B have also been carried out. Finally, the lipid peroxidation biomarker (TBARS) and oxyLDL were also measured.ResultsBPF prevented tChol, LDL-C, TG and fasting plasma glucose enhancement and improved HDL-C. Treatment of hyperlipæmic rats with BPF significantly restored altered the serum concentration of lipemic biomarkers and the activity of ACAT, LCAT, CETP and PON1, an effect accompanied by the concomitant normalization of Apo A1 and APO B levels. In addition, TBARS levels were reduced significantly by the treatment with BPF.ConclusionsBPF prevents diet-induced alteration of the lipid profile in rats, counteracting oxidative stress and improving the dysregulation of the Lipid Transfer Protein System. These data add new insights into the molecular mechanisms underlying the beneficial role of BPF in the therapy of hyperlipidaemia, thus suggesting a novel approach in the prevention of cardiovascular disease.

Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction.

Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress.

Detailed Phytochemical Characterization of Bergamot Polyphenolic Fraction (BPF) by UPLC-DAD-MS and LC-NMR.

Bergamot ( Citrus bergamia) is cultivated in Southern Italy almost exclusively to produce the prized essential oil, a top note in several perfumes. The juice of bergamot, until recently poorly studied, is the object of a growing scientific interest due to its claimed activity to treat metabolic syndrome. The aim of this investigation was a detailed characterization of bergamot juice polyphenolic fraction (BPF) based on a UPLC-DAD-MS analysis complemented by preparative chromatographic separations, followed by NMR characterization of the isolated compounds. The combination of these techniques efficiently covered different classes of secondary metabolites, leading to the identification of 39 components, several of which had never been reported from bergamot. One of them, bergamjuicin (35), is a new flavanone glycoside, whose structure has been determined by MS and NMR techniques. The reported results could provide a guide for future routine analyses of BPF, a material of great nutraceutical and industrial interest.

Hypoglycemic and Hypolipemic Effects of a New Lecithin Formulation of Bergamot Polyphenolic Fraction: A Double Blind, Randomized, Placebo- Controlled Study.

Hyperlipemia represents an independent risk factor in the development of atherosclerosis in patients undergoing type 2 diabetes mellitus (DM). Moreover, the pharmacological treatment of dyslipemia in patients undergoing type 2 DM (e.g. by means of statins), is accompanied by relevant side effects and oral supplementation with natural antioxidants, such as Citrus polyphenols, has recently been suggested to improve cardioprotection in such patients. However, due to the poor gastrointestinal absorption of polyphenols, novel formulations have recently been developed for getting a better bioavailability of polyphenolic rich fractions of citrus species extract rich in polyphenols. Here, we investigated the effect of standard bergamot polyphenolic fraction (BPF®) as well as of its phytosomal formulation (BPF Phyto), in patients with type 2 DM and hyperlipemia. A randomized, double blind, placebo-controlled study was carried out in 60 patients suffering from type 2 DM and mixed hyperlipemia. Patients were divided into three groups: one receiving placebo, the second receiving standard BPF and the third BPF Phyto. In the groups receiving BPF and BPF Phyto, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides accompanied by increased HDL cholesterol was observed. This effect was associated with significant reduction of small dense atherogenic LDL particles, as detected by means of proton NMR Spectroscopy, thus confirming the hypolipemic and hypoglycemic effect of bergamot extract both when using standard formulation as well as BPF Phyto. No differences were seen in the therapeutic response among groups receiving BPF and BPF Phyto, thus suggesting a substantial bioequivalence in their hypoglycemic and hypolipemic profile. However, when comparing the pharmacokinetic profile of naringin (the major component of BPF) and its metabolites, in patients treated with BPF Phyto, an at least 2,5 fold increase in its absorption was found, confirming in human studies the better profile of BPF Phyto compared to standard BPF. These data suggest that better absorption and tissue distribution of BPF Phyto formulation represents an innovative approach in supplementation treatments of cardiometabolic disorders.

Stanowisko grupy ekspertów wsparte przez Sekcję Farmakoterapii Sercowo-Naczyniowej Polskiego Towarzystwa Kardiologicznego dotyczące miejsca standaryzowanej kompozycji polifenoli z bergamoty w terapii dyslipidemii oraz jej innego potencjalnego zastosowania

Bergamot juice has a particularly high content and a unique composition of flavonoids. It is particularly rich in flavanones and flavones. Standardized bergamot polyphenolic fraction has the same polyphenol profile as in the juice, but flavonoids are over 200 times more concentrated. Many data show its brilliant performance in hyperlipidaemia and moderate hyperglycaemia. In addition, it has other beneficial pleiotropic properties. The following document contains the opinion of an expert group summarizing current knowledge on bergamot flavonoids and their possible use in selected populations of patients.

Bergamot Polyphenolic Fraction supplementation improves metabolic balance, endothelial function and maximal oxygen uptake in athletes

Bergamot Polyphenolic Fraction supplementation improves metabolic balance, endothelial function and maximal oxygen uptake in athletes

Cognitive outcomes of Bergamot Polyphenolic Fraction (BPF) supplementation in schizophrenia: Preliminary data

BackgroundCognitive deficits in schizophrenia significantly affect illness and community outcomes, and quality of life. Several studies support the neuroprotective properties of polyphenolic compounds resulting in neuronal protection, suppression of neuroinflammation and the potential to promote memory, learning and cognitive functions. Bergamot differs from other citrus fruits for flavonoids and flavonoid glycosides composition (neoeriocitrin, neohesperidin, naringin, rutin, neodesmina, roifolina and poncirina), and for their high amount. For these features, BPF may represent a potential supplement for improving cognitive functions.AimsThe present study was aimed to explore the efficacy of BPF supplementation on clinical symptoms andcognitive functioning in a sample of schizophrenic subjects receiving atypical antipsychotics (APs).MethodsTen schizophrenic outpatients treated with atypical APs assumed BPF at the oral daily dose of 1000 mg/day for 30 days. Brief Psychiatric Rating Scale, Wisconsin Card Sorting Test, Verbal Fluency Task-Controlled Oral Word Association Test, and Stroop Color-Word Test were administered.ResultsThe results obtained indicate that BPF administration substantially improved WCST performances (perseverative responses, P = 0.008; perseverative errors, P = 0.012; total errors, P = 0.011; categories, P = 0.023). Moreover, a trend for others clinical (BPRS) and cognitive variables (Verbal Fluency Task-Controlled Oral Word Association Test, and Stroop Color-Word Test) decrease was observed.ConclusionsThe findings provide evidence that BPF administration may be proposed as an effective therapeutic strategy to improve cognitive outcome in schizophrenia. Further clinical trials with adequately powered and well-designed methodology are needed to better explore the BPF effectiveness on cognitive impairments in schizophrenic patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Metabolic outcomes of bergamot polyphenolic fraction administration in patients treated with second-generation antipsychotics: a pilot study

Second-generation antipsychotics (SGAs) are notoriously associated with a marked increase in body weight and with a wide range of metabolic adverse effects, and their chronic use is related with an increased risk for the development of metabolic syndrome (MS). Different adjunctive treatments have been proposed to reduce SGAs-induced weight gain and/or metabolic abnormalities with inconsistent or too limited evidence to support their regular clinical use, thus suggesting the need to find new possible treatments. Bergamot polyphenolic fraction (BPF) has been proven effective in patients with MS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to explore the efficacy and safety of BPF treatment on metabolic parameters in a sample of subjects receiving atypical antipsychotics. Fifteen outpatients treated with SGAs assumed BPF at the oral daily dose of 1000 mg/day for 30 days. Fasting levels of glucose, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides were determined. BPF administration resulted in a statistically significant reduction of body weight (P=.004) and in a trend for body mass index decrease (P=.005). No significant differences in other and metabolic parameters were observed. Our findings suggest that BPF, at the daily dose of 1000 mg for 30 days, could be an effective and safe agent to prevent weight gain associated with atypical antipsychotic use. However, further clinical trials with adequately powered and well-designed methodology are needed to better explore the BPF effectiveness on the SGAs-induced weight gain and metabolic side effects.

Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice.

Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5–50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy.

Characterization of flavonoids in Citrus bergamia (Bergamot) polyphenolic fraction by liquid chromatography–high resolution mass spectrometry (LC/HRMS)

The goal of the present study was the development of a UHPLC-HRMS/MS method for the identification of flavonoids present in BPF (bergamot polyphenolic fraction), a particular product derived from Bergamot juice. BPF contains over 40% flavonoids and the remaining 60% are carbohydrates, fatty acids, pectins and other compounds as well as maltodextrins which are added to allow exsiccation. Trademark and patent No. 0001380456 by Herbal and Antioxidant Derivatives S.R.L. The mass spectrometry data, obtained with an Orbitrap spectrometer, reveal the presence of principal flavonoids neoeriocitrin, naringin, neohesperidin but also of all HMG-family like bruteridin, melitidin with other HMG species and flavonoids 6,8-di-C-glicosides too. The method permits to reveal all species in high resolution full scan and to confirm their identities by HRMSMS (ddMS2, data dependent MSMS) in the same event.

Bergamot polyphenolic fraction potentiates rosuvastatin induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia

Bergamot polyphenolic fraction potentiates rosuvastatin induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia

Effect of Citrus Bergamot Polyphenol Extract on Patients With Nonalcoholic Fatty Liver Disease

Introduction: To determine whether bergamot polyphenolic fraction (BPF), a proprietary extract from a unique antioxidant-rich citrus fruit (bergamot) known to be beneficial in subjects with metabolic syndrome and dyslipidemias, could significantly improve hepatic structure and function in patients with both metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Methods: One hundred seven patients who met the NCEP-ATP III criteria for metabolic syndrome and had ultrasonic evidence of severe NAFLD (hepato-renal index 2.5-3.5) after exclusion of alcohol, viral, and immune disorders were admitted to the study. Before and after 120 days of BPF 650 mg twice a day, all patients had full lipid analysis including lipoprotein fractionation (NMR), fasting glucose, ALT, AST, steato test, γ-GT, TNF-α (ELISA), CRP, and ultrasonographic hepatorenal tests. Results: Hepatic tests include: steato test (baseline: 0.74 ± 0.12; after 120 days BPF: 0.44 ± 0.09), ALT (U/L) (baseline: 54 ± 5.4; after 120 days BPF: 36 ± 5.3), AST (U/L) (baseline: 52. ± 6.4; after 120 days BPF: 41 ± 5.2), γ-GT (IU/L) (baseline: 38 ± 5.2; after 120 days BPF: 29.33 ± 1.1), hepatorenal index (baseline: 2.8 ± 0.4; after 120 days BPF: 1.5 ± 0.5). Inflammatory tests include: Hs-CRP (mcg/dL) (baseline: 1.2 + 0.8; after 120 days BPF: 0.94 + 0.6) and TNF-α (pg/mL) (baseline: 14.4 ± 1.9; after 120 days BPF: 10.7 ± 1.7). Metabolic tests include: fasting glucose (mg/mL) (baseline: 118 ± 1.4; after 120 days BPF: 98 ± 0.8). All values p<0.05. Standard lipid levels (TC, LDL, HDL, TG, IDL, VLDL) were significantly improved as were the size, density and number of all atherogenic lipoprotein particles (e.g., small dense LDL, NMR, LDL particle number). Conclusion: Bergamot polyphenolic extract (BPF) derived from the Calabrian bergamot citrus fruit is a potent anti-oxidant, AMP kinase activator, and HMG-CoA reductase inhibitor that has been proven to address all components of the metabolic syndrome. In a group of 107 patients with confirmed NAFLD and metabolic syndrome, BPF given twice per day before meals significantly improved all measured biochemical and ultrasonographic characteristics of both NAFLD and metabolic syndrome in 120 days without reported side effects. There was a striking improvement in hepatic function (biochemical) and structure (echogenic visual loss of hepatic fat) accompanied by lower levels of inflammation. As there is a dearth of proven therapeutic options for NAFLD and metabolic syndrome, this study suggests that BPF may be a safe and important therapeutic option for these conditions. Disclosure - James E. Ehrlich--consultant for Nat Health Solutions, distributor of BergaMet. Ross Walker--consultant for Nat Health Solutions. Vincenzo Mollace--consultant for Nat Health Solutions.Figure 1

The Effect of Bergamot-Derived Polyphenolic Fraction on LDL Small Dense Particles and Non Alcoholic Fatty Liver Disease in Patients with Metabolic Syndrome

The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.

Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia

BackgroundStatins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia. MethodsA prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n=15), two groups receiving orally administered rosuvastatin (10 and 20mg/daily for 30days; n=16 for each group), a group receiving BPF alone orally (1000mg/daily for 30days; n=15) and a group receiving BPF (1000mg/daily given orally) plus rosuvastatin (10mg/daily for 30days; n=15). ResultsBoth doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accompanied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells. ConclusionsAddition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy.