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The components of Bergavit® separated by high-performance liquid chromatography (HPLC-DAD Analysis 280 nm), as determined by Bionap. The chromatographic analyses are determined on a Shimadzu LC system by Bionap.
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Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be...
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... admission they underwent a medical examination and were excluded from the study if they had clinical evidence of severe hepatic or renal diseases. All subjects received daily Bergamot derived flavonoid extract, Bergavit R (Bionap, Italy), containing 150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin, and 37% of naringin (as determined by Bionap, see Figure 1), for 6 months. All medical and biochemical procedures were performed at baseline and after 6 months of supplementation. ...
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... found a significant modification in plasma lipoprotein subfractions after Bergavit R supplementation that is somewhat consistent with our previous study where the effects of another nutraceutical (chitosan) was assessed in patients with hypertriglyceridemia [TG > 150 mg/dl (>3.9 mmol/l)] ( Rizzo et al., 2014), as well as with other studies that used different nutraceuticals [as reviewed in (Patti et al., 2015)]. In the present study we found that small dense LDL particles (LDL3, -4, and -5) decreased, which may decrease CV risk ( Mikhailidis et al., 2011a). ...
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... mechanisms are involved in the enhanced atherogenicity of small dense LDL, including the increased filtration through the endothelium, a reduced LDL receptor affinity as well as a prolonged circulation time and higher proteoglycan binding; further, the oxidative modification of LDL is recognized as the key step in the atherothrombotic process, and small dense LDL exhibit enhanced oxidative susceptibility and lower levels of antioxidants ( Rizzo and Berneis, 2006a,b;Rizzo et al., 2007;Nikolic et al., 2013;Garcia-Rios et al., 2014). In addition, in the last years a large number of studies, including epidemiologic studies as well as clinical intervention trials, have reported a strong association between CV risk and small, dense LDL; this topic has been reviewed and discussed by the European Panel of experts in a Consensus Statement on the pathophysiology, atherogenicity and clinical significance of LDL subclasses (Mikhailidis et al., 2011a). However, the mechanism by which the LDL particle shifts to a larger size cannot be fully discerned from these data. ...
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Background: In chronic kidney disease (CKD) patients,measuring carotid artery intima– media thickness (CIMT) canpredict coronary heart disease and stroke, resulting from systemic atherosclerosis.Objective: To find out correlation of carotid artery intima–media thickness and dyslipidemia in chronic kidney disease in a Bangladesh population.Methods:...
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... 44 Phytochemicals, such as flavonoids has been shown to decrease lower serum lipids levels by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme and up-regulating peroxisome proliferators-alpha and gamma expressions in the liver. 45 Flavanoids prevent the oxidation of low-density lipoprotein, lowers the blood lipid levels thereby reducing the risk for the development of atherosclerosis. It has been suggested that consumption of tannin containing food and beverages, can prevent a variety of ailments such as heart related diseases. ...
Grewia mollis Juss (Malvaceae) commonly described as “Dargaza” is a shrub, popularly used in folk medicine to treat obesity, diarrhoea and to ease childbirth. However, there are no established reports on its antiobesity activity in literature, hence, the aim of the study was to evaluate the antihyperlipidemic and antiobesity effects of Grewia mollis (GM) in rodents. Hyperlipidemia was induced by 200 mg/kg of triton WR-1339 and the rats were orally pre-treated with extract (150-600 mg/kg) and atorvastatin (25 mg/kg) for 3 days. Obesity was induced with dietary cholesterol (600 mg/kg) for 10 weeks and rats were orally treated with extract (150-600 mg/kg). The effects of the extract on body weight, total food consumption, relative organ weight, Lee index, lipid profile, atherogenic index, coronary risk index and histopathological indices were evaluated. Preliminary phytochemical screening showed presence tannins, saponins, alkaloids, flavonoids and steroidal nucleus. The extract significantly (p<0.05) decreased total cholesterol, triglyceride, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL), non-high-density lipoprotein cholesterol, atherogenic index, coronary risk index in hyperlipidemic rats. In the obese rat, there was significant (p<0.05) decrease in relative liver weight, body weight, Lee index, triglycerides, VLDL. Atherosclerotic changes in the coronary artery and aorta were ameliorated by the extract. The reduction in lipid profile and amelioration of atherosclerotic lesions indicate a possible anti-atherogenic property. These effects appear to be mediated via inhibition de novo triglyceride and cholesterol biosynthesis. The extract shows therapeutic promise in the management of obesity, hyperlipidemia and in the prevention of atherosclerosis.
... Bergamot has been used in numerous clinical trials and has consistently been shown to be well tolerated in studies lasting from 30 days to 12 weeks. For example, a randomized double-blind placebo-controlled study by Toth et al. [151] assessed the hypolipidemic effects of a bergamot polyphenol fraction. The bergamot polyphenol fraction decreased total cholesterol from 262 to 196, LDL cholesterol from 175 to 116, and triglycerides from 252 to 170. ...
... Polyphenols have been found to modulate over 100 miRNAs, which play a role in regulating various cellular processes such as inflammation and apoptosis. Some of the polyphenols that have been reported to exert their effects through microRNAs include naringenin, apigenin, kaempferol, hesperidin, ellagic acid, and oleuropein [150,151]. The majority of the research on this subject has been conducted in vitro using various cell lines, particularly cancer cell lines. ...
Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases.
... Bergamot (Citrus bergamia, C. bergamia) is a Mediterranean citrus fruit typical of Calabria (southern part of Italy), that has raised increasing attention due to its rich bioactive molecules composition and unique profile made of flavonoid glycosides, including neoeriocitrin, neohesperidin, naringin and glycosylated polyphenols, such as brutieridin and melitidin (Salerno et al., 2016). Mainly bergamot juice and its derivates, originally considered a by-product of essential oil extraction used in cosmetic and food industries, have been characterised as promising sources of biomolecules with favourable health-related functions (Ferlazzo et al., 2016;Navarra et al., 2014;Toth et al., 2016). More recently, other parts of the plant-like peel extracts have been studied for their promising multiple health-related properties (Benavente-Garcia & Castillo, 2008;Mannucci et al., 2017;Navarra et al., 2015). ...
... In particular, the Brumex™ treated subjects experienced a significant 7.8 ± 1.2% decrease in TC, 7.6 ± 1.1% in low-density Although preliminary evidence on bergamot's beneficial properties-in terms of lipid-lowering capability-has been envisaged, we here provide an integrated preclinical and clinical study based on a commercial bergamot extract (Brumex™). It is peculiarly obtained from different parts of the whole fruit, mainly from bergamot juice, rather than from bergamot juice and/or based on single polyphenolic active components, as mostly demonstrated in literature data (Ferlazzo et al., 2016;Navarra et al., 2014;Toth et al., 2016). In our study, we prove the effectiveness of a whole bergamot extract that is specifically rich in neoesperidin, neoeriocitrin, naringin, brutieridin and melitidin flavonoids, with a peculiar HPLC profile of HMG-Flavanones ≥5% w/w ( Figure S1). ...
With the aim of characterising the hypo-lipidemic function of the Brumex™ ingredient obtained from the whole fruit of Citrus bergamia, a combined pre-clinical and clinical study was conducted. In the HepG2 experimental model, we first demonstrated that Brumex™ does not trigger any significant alteration in cell viability over the tested concentration range of 1-2000 μg/mL (4 and 24 h). By stimulating the phosphorylation of AMP-activated protein kinase (AMPK) at threonine 172, Brumex™ significantly reduces both cholesterol and triglyceride (TG) intracellular content of HepG2 cells and impairs the expression levels of lipid synthesis-related genes (namely, SREBF1c, SREBF2, ACACA, SCD1, HMGCR and FASN). In vitro data have been validated in a dedicated double-blind, placebo-controlled, randomised clinical trial performed in 50 healthy moderately hyper-cholesterolemic subjects, undergoing supplementation with either Brumex™ (400 mg) or placebo for 12 weeks. Clinical and blood laboratory data were evaluated at the baseline and at the end of the trial. Brumex™ positively impacted on both plasma lipid pattern and liver enzymes compared with the placebo, mainly in terms of significant reduction of total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein B100 (ApoB), fasting plasma glucose (FPG), glutamic-oxaloacetic transaminase (GOT), glutamate pyruvate transaminase (GPT) and gamma-glutamyl-transferase (gGT).
... 55 According to several studies, (66,67,68,69,70,71) flavonoids are substances that are found in various plant matrices. According to studies, 72 a cardio protective effect with a 150 mg daily dose, 73 and a robust improvement of dyslipidemia (reduction of triglycerides, total cholesterol, and low-density lipoprotein cholesterol), are flavonoids in bergamot albedo and juice. 74 Bergamot juice and hazy juice contain the highest representative flavonoids. ...
Celtis tournefortii Lam and Prosopis farcta plant's antioxidant and polyphenolic characteristics have been attributed to the various phytochemicals, including phenolic and fatty acids, present in the crude extract in the leaves, fruits, pods, and seeds. This study's aim is to determine the entire phytochemical compositions of the leaf and fruit reflect Celtis tournefortii Lam, while pod and seed represent Prosopis farcta from Mazne sub-district, including proximate analysis, total antioxidant capacity, total organic acids, ascorbic acids, polyphenols, and fatty acids following established procedures. Pods have higher levels of fiber (41± 0.05 mg/100 g), protein (20.3±0.05%), and vitamin C (26.47±0.03 mg/100 g) from Prosopis farcta, although fruit has higher levels of total antioxidants (89.54± 0.28%) and organic acid (1576±0.57 mg/kg) from Celtis tournefortii Lam. Gallic acid (10.56±0.03 mg/kg) had the highest concentration of polyphenols, whereas the pod contained the highest concentrations of quercetin (11.27±0.14 mg/kg), rutin (13.0±0.57 mg/kg), coumaric acid (2140.57 mg/kg), and chlorogenic acid (659.0±0.57 mg/kg). Oleic acid 32.60±0.24%, Cis-11-Eicosenoic 3.20±0.11%, and Cis-4,7,10,13,16,19-Docosahexaenoic 2.10±0.05% were the most prevalent unsaturated fatty acids in the seed, whereas palmitic 17.40±0.05% and tricosanoic 6.40±0.05% were the most prevalent saturated fatty acids in the leaves. Overall, seeds had the highest concentration of unsaturated fatty acids (74.44%), while leaves had the highest concentration of saturated fatty acids (44.42%). This study identifies two untamed plants, Celtis tournefortii Lam and Prosopis farcta, as potential new sources of natural oil and beneficial natural ingredients.
... To optimize the impact of the bergamot products as food supplements, different preparations and formulations must be assessed for their biologically active effects. In addition to BEO (Watanabe et al. 2015), the main preparations commonly used include bergamot extract (BE) (Toth et al. 2015) obtained from BJ and/or fruit pulp, and the bergamot polyphenolic fraction (BPF), which is enriched in polyphenols, such as neoeriocitrin, neohesperidin, and naringin (Toth et al. 2015;Bruno et al. 2017). This last formulation, which has generated considerable nutraceutical and industrial interest, has been widely characterized via ultra-performance liquid chromatography with diode array detection mass spectrometry analysis. ...
... To optimize the impact of the bergamot products as food supplements, different preparations and formulations must be assessed for their biologically active effects. In addition to BEO (Watanabe et al. 2015), the main preparations commonly used include bergamot extract (BE) (Toth et al. 2015) obtained from BJ and/or fruit pulp, and the bergamot polyphenolic fraction (BPF), which is enriched in polyphenols, such as neoeriocitrin, neohesperidin, and naringin (Toth et al. 2015;Bruno et al. 2017). This last formulation, which has generated considerable nutraceutical and industrial interest, has been widely characterized via ultra-performance liquid chromatography with diode array detection mass spectrometry analysis. ...
Context: Bergamot, mainly produced in the Ionian coastal areas of Southern Italy (Calabria), has been used since 1700 for its balsamic and medicinal properties. Phytochemical profiling has confirmed that bergamot juices are rich in flavonoids, including flavone and flavanone glycosides which are responsible for its beneficial effects.
Objective: Recently, it was shown that the combination of natural compounds with conventional treatments improves the efficacy of anticancer therapies. Natural compounds with anticancer properties attack cancerous cells without being toxic to healthy cells. Bergamot can induce cytotoxic and apoptotic effects and prevent cell proliferation in various cancer cells.
Methods: In this review, the antiproliferative, pro-apoptotic, anti-inflammatory, and antioxidant effects of bergamot are described. Information was compiled from databases such as PubMed, Web of Science, and Google Scholar using the key words ‘bergamot’ accompanied by ‘inflammation’ and, ‘cancer’ for data published from 2015–2021.
Results: In vitro and in vivo studies provided evidence that different forms of bergamot (extract, juice, essential oil, and polyphenolic fraction) can affect several mechanisms that lead to anti-proliferative and pro-apoptotic effects that decrease cell growth, as well as anti-inflammatory and antioxidant effects.
Conclusions: Considering the effects of bergamot and its new formulations, we affirm the importance of its rational use in humans and illustrate how bergamot can be utilized in clinical applications. Numerous studies evaluated the effect of new bergamot formulations that can affect the absorption and, therefore, the final effects by altering the therapeutic profile of bergamot and enhancing the scientific knowledge of bergamot.
... As a result, the bergamot extracts reduced plasma lipids and improved the lipoprotein profile. Remarkably, a reduced subclinical atherosclerosis (assessed as carotid intimal media thickness) was observed [49]. ...
High salt load is a known noxious stimulus for vascular cells and a risk factor for cardiovascular diseases in both animal models and humans. The stroke-prone spontaneously hypertensive rat (SHRSP) accelerates stroke predisposition upon high-salt dietary feeding. We previously demonstrated that high salt load causes severe injury in primary cerebral endothelial cells isolated from SHRSP. This cellular model offers a unique opportunity to test the impact of substances toward the mechanisms underlying high-salt-induced vascular damage. We tested the effects of a bergamot polyphenolic fraction (BPF) on high-salt-induced injury in SHRSP cerebral endothelial cells. Cells were exposed to 20 mM NaCl for 72 h either in the absence or the presence of BPF. As a result, we confirmed that high salt load increased cellular ROS level, reduced viability, impaired angiogenesis, and caused mitochondrial dysfunction with a significant increase in mitochondrial oxidative stress. The addition of BPF reduced oxidative stress, rescued cell viability and angiogenesis, and recovered mitochondrial function with a significant decrease in mitochondrial oxidative stress. In conclusion, BPF counteracts the key molecular mechanisms underlying high-salt-induced endothelial cell damage. This natural antioxidant substance may represent a valuable adjuvant to treat vascular disorders.
... Oral administration of bergamot extract (150 mg containing 16% neohesperidin, 47% neohesperidin, and 37% naringin) for 6 months reduced moderate hypercholesterolemia, low-density lipoprotein, and blood lipids in patients with atherosclerosis [110]. Neohesperidin activated the AMPK pathway for hypoglycemic and exhibited lipid-lowering effects [111]. ...
Flavonoids derived from citrus plants are favored by phytomedicinal researchers due to their wide range of biological activities, and relevant studies have been sustained for 67 years (since the first paper published in 1955). In terms of a scientometric and critical review, the scientometrics of related papers, chemical structures, and pharmacological action of citrus flavonoids were comprehensively summarized. The modern pharmacological effects of citrus flavonoids are primarily focused on their anticancer activities (such as breast cancer, gastric cancer, lung cancer, and liver cancer), neuroprotective effects (such as anti-Alzheimer’s disease, Parkinson’s disease), and metabolic diseases. Furthermore, the therapeutic mechanism of cancers (including inducing apoptosis, inhibiting cell proliferation, and inhibiting cancer metastasis), neuroprotective effects (including antioxidant and anti-inflammatory), and metabolic diseases (such as non-alcoholic fatty liver disease, type 2 diabetes mellitus) were summarized and discussed. We anticipate that this review could provide an essential reference for anti-cancer and neuroprotective research of citrus flavonoids and provide researchers with a comprehensive understanding of citrus flavonoids.
... In this context, functional foods and nutraceuticals have a wide range of applications. It is widely recognized that, due to the antioxidant and anti-inflammatory properties of many natural substances, chronic consumption of nutraceuticals in every-day clinical practice can improve the outcome in patients with atherosclerosis, type 2 diabetes mellitus, obesity, and dyslipidemia [6][7][8][9][10]. Furthermore, evidence supports the hypothesis that multiple natural product combinations may result in a synergistic activity that increases their bioavailability and action on multiple molecular targets, offering considerable advantages over a single consumption [11,12]. ...
Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and < 30 kg/m2. All subjects received the Altilix® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects.
... Also, ginseng that aid in lowering the choles- terol and LDL-C by inhibition of -hydroxy--methylglutaryl-CoA reductase ( Sotaniemi et al., 1995 ). Bergamot juice has significant effects on metabolic markers, as atherogenic lipoproteins, subclinical atherosclerosis, and plasma lipids ( Toth et al., 2016 ). Mulberry leaf extract has impact on MetS by decreasing postprandial glucose, triglycerides, LDL-C and increasing HDL-C ( Kojima et al., 2010 ). ...
Metabolic syndrome (MetS) is a bunch of metabolic defects comprising hypertension, insulin resistance, visceral obesity, fatty liver, and atherogenic cardiovascular diseases. Lifestyle modification is the first step for controlling the MetS progression. If left untreated, MetS is significantly related to a high danger of evolving type 2 diabetes and atherogenic cardiovascular diseases. Thus, MetS is a prominent cause of morbidity and mortality internationally and has been become very important to investigate novel therapies in this context to decrease the heavy burden of the disease. Though, there is no single treatment for MetS and the currently available pharmacother-apy and related comorbidities demand the continued use of multiple drugs that is challenging for patients as the polypharmacy and reduced accordance. There is increasing concern in the use of nutraceuticals in the management of MetS. This review follows MetS with an emphasis on the risk factors and how to control it, epidemiology, pathogenesis, pathophysiology, diagnosis, and treatments. Moreover, the review recaps on the health benefits of natural products in the management of the MetS to give a complete guide to other researchers for new natural products investigation. Novelty Statement MetS is significantly related to develop type 2 diabetes and car-diovascular diseases as well as MetS is considered a prominent reason of morbidity and mortality worldwide. Thus, it is critical to explore new treatments in this circumstance. However, there is no single treatment for MetS and the existing pharmacotherapy require the continuous use of numerous drugs that is challenging for patients as the polypharmacy and diminished accordance. There is rising interest in the utilization of nutraceuticals in the management of MetS. Also, the investigation of an efficient approach to manage those complications not studied well, where the authors highlighted this point in our manuscript. We presented in this review a wide information concerning the risk factors, patho
... Several in vitro and in vivo studies have demonstrated the protective effect on the cardiovascular, nervous, respiratory, and gastrointestinal systems of honey (Al-Waili, 2003;Alvarez-Suarez et al., 2013). For instance, honey has been shown to increase antioxidant status (Toth et al., 2016) and improve blood lipid profiles in healthy, overweight, and hyperlipidemic patients (Al-Waili, 2004;Yaghoobi et al., 2008). These characteristics qualify it as a possible sweetener alternative for domestic use and the food industry since the literature shows that it has greater nutritional properties than refined sugars (Carocho et al., 2017). ...
The monofloral avocado honey (AH), characterized by its dark amber color, contains a higher level of bioactive compounds than the multi-floral honey; these characteristics qualify it as a possible sweetener alternative for domestic use. Therefore, the purpose of the present study was to assess the effect of the consumption of avocado honey (25 g/day) on anthropometric and biochemical parameters in healthy subjects for 4-weeks. Thirteen healthy subjects (control group: n = 7 or honey group n: 6) aged 25–50 years, with BMI (body mass index): <25 kg/m2 completed the study (ClinicalTrials.gov: NCT04572607). There was no significant difference in BMI and body fat percentage. Likewise, no effects on fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected. These data suggest that AH might be as effective as a functional food or natural sweeter without negatively influencing anthropometric and biochemical parameters.
