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Keywords = Bergamot Polyphenolic Fraction

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41 pages, 1846 KiB  
Review
The Potential of Nutraceutical Supplementation in Counteracting Cancer Development and Progression: A Pathophysiological Perspective
by Carmen Altomare, Roberta Macrì, Maria Serra, Sara Ussia, Giovanna Ritorto, Jessica Maiuolo, Carolina Muscoli, Enzo Perri and Vincenzo Mollace
Nutrients 2025, 17(14), 2354; https://doi.org/10.3390/nu17142354 - 18 Jul 2025
Viewed by 659
Abstract
Cancer is a major cause of morbidity and mortality across the globe, with a substantial increase in cases anticipated over the next few decades. Given the constraints and adverse effects associated with standard cancer therapies, the contribution of diet and nutraceuticals to cancer [...] Read more.
Cancer is a major cause of morbidity and mortality across the globe, with a substantial increase in cases anticipated over the next few decades. Given the constraints and adverse effects associated with standard cancer therapies, the contribution of diet and nutraceuticals to cancer prevention and treatment is receiving increased scrutiny. A diet rich in plant-based foods, extra virgin olive oil (EVOO), and bioactive compounds, including the Mediterranean Diet, has been associated with reduced cancer risk and improved treatment outcomes. This review aims to explore the complex mechanisms of the MedDiet and nutraceuticals (polyphenols, flavonoids, terpenoids) in cancer prevention, to determine their potential as cancer treatment adjuvants. Promising results show that key compounds such as bergamot polyphenolic fraction (BPF), cynaropicrin, oleuropein, quercetin, resveratrol, and serotonin can modulate oxidative stress, inflammation, the tumor microenvironment, the cell cycle, and drug resistance. A significant observation is that many of these substances demonstrate dual dose-dependent activity; they function as antioxidants in healthy cells but induce pro-oxidant and pro-apoptotic effects in cancerous cells. Their ability to boost chemotherapy’s effectiveness and safety while lessening side effects and offering combined advantages is also explored. To summarize, this review suggests that the Mediterranean Diet and nutraceutical supplements may help prevent and manage cancer, but more research is needed to confirm their benefits. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health—2nd Edition)
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15 pages, 1619 KiB  
Article
The Antioxidant Power of Bergamot Polyphenolic Fraction Gold Potentiates the Effects of L-Citrulline in Athlete Performance and Vasodilation in a Pilot Study
by Rocco Mollace, Roberta Macrì, Maria Serra, Giovanna Ritorto, Sara Ussia, Federica Scarano, Antonio Cardamone, Vincenzo Musolino, Anna Rita Coppoletta, Micaela Gliozzi, Giuseppe Scipione, Cristina Carresi, Kateryna Pozharova, Carolina Muscoli, Francesco Barillà, Maurizio Volterrani and Vincenzo Mollace
Nutrients 2025, 17(7), 1106; https://doi.org/10.3390/nu17071106 - 21 Mar 2025
Viewed by 1362
Abstract
Background: The dietary supplement citrulline might increase nitric oxide levels, leading to vasodilation and improved blood flow, potentially benefiting athletes’ aerobic exercise performance. However, rapid oxidative impairment of the L-arginine/nitric oxide (NO) pathway limits these effects. This is countered by Bergamot Polyphenolic Fraction [...] Read more.
Background: The dietary supplement citrulline might increase nitric oxide levels, leading to vasodilation and improved blood flow, potentially benefiting athletes’ aerobic exercise performance. However, rapid oxidative impairment of the L-arginine/nitric oxide (NO) pathway limits these effects. This is countered by Bergamot Polyphenolic Fraction Gold® (BPFG), a strong natural antioxidant. To investigate L-citrulline + BPFG supplementation’s effects, we performed a randomized, double-blind, placebo-controlled pilot trial on athletic performance and blood flow in trained athletes (cyclists). Methods: Random assignment of 90 male athletes resulted in nine different groups: placebo for Group 1, BPFG at 500 and 1000 mg daily for Groups 2 and 3, L-citrulline at 1000 and 2000 mg/daily for Groups 4 and 5, and the combination product of BPFG plus citrulline (N.O. Max) for Groups 6–9. Baseline and 3-month pre- and post-exercise biochemical, reactive vasodilation (RHI), and maximal oxygen consumption measurements were taken for all subjects. Results: Three months of the combination of BPFG and L-citrulline (N.O. Max) produced a significant synergistic effect, markedly increasing NO (p < 0.001 vs. placebo) release and RHI (p < 0.001 vs. placebo). Cardiorespiratory fitness improved significantly with the BPFG and L-citrulline combination, resulting in substantially higher VO2 max, VT1, VT2, and peak power and a significantly lower heart rate (p < 0.01 vs. placebo). No harmful adverse effects were observed. Conclusions: N.O. Max supplementation, providing beneficial effects on the antioxidant state and preserving the vascular endothelium might be a supplementation strategy to improve athletic performance and potentiate results. Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale. Full article
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18 pages, 4636 KiB  
Article
Exploring the Role of Bergamot Polyphenols in Alleviating Morphine-Induced Hyperalgesia and Tolerance through Modulation of Mitochondrial SIRT3
by Sara Ilari, Saverio Nucera, Lucia Carmela Passacatini, Federica Scarano, Roberta Macrì, Rosamaria Caminiti, Stefano Ruga, Maria Serra, Luigino Antonio Giancotti, Filomena Lauro, Concetta Dagostino, Valeria Mazza, Giovanna Ritorto, Francesca Oppedisano, Jessica Maiuolo, Ernesto Palma, Valentina Malafoglia, Carlo Tomino, Vincenzo Mollace and Carolina Muscoli
Nutrients 2024, 16(16), 2620; https://doi.org/10.3390/nu16162620 - 9 Aug 2024
Cited by 3 | Viewed by 1715
Abstract
Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 [...] Read more.
Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects. Full article
(This article belongs to the Special Issue Effects of Natural Bioactives on Pain and Neuroinflammation)
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19 pages, 5721 KiB  
Article
Dramatic Suppression of Lipogenesis and No Increase in Beta-Oxidation Gene Expression Are among the Key Effects of Bergamot Flavonoids in Fatty Liver Disease
by Maddalena Parafati, Daniele La Russa, Antonella Lascala, Francesco Crupi, Concetta Riillo, Bartosz Fotschki, Vincenzo Mollace and Elzbieta Janda
Antioxidants 2024, 13(7), 766; https://doi.org/10.3390/antiox13070766 - 25 Jun 2024
Cited by 3 | Viewed by 2904
Abstract
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes [...] Read more.
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed a RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of bergamot polyphenol fraction (BPF). CAF diet caused a strong upregulation of gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6, Il10, Tnf). However, only one β-oxidation gene (Cpt1a) and a few autophagy genes were differentially expressed in CAF rats compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca and Fasn, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no β-oxidation gene expression changes were observed compared to CAF group. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on β-oxidation, but profound suppression of de novo lipogenesis. Full article
(This article belongs to the Special Issue The Role of Oxidative Stress in Non-Alcoholic Fatty Liver Disease)
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13 pages, 756 KiB  
Article
A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels
by Federica Fogacci, Marina Giovannini, Antonio Di Micoli, Giulia Fiorini, Elisa Grandi, Claudio Borghi and Arrigo F. G. Cicero
Nutrients 2024, 16(11), 1587; https://doi.org/10.3390/nu16111587 - 23 May 2024
Cited by 5 | Viewed by 5102
Abstract
The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke—both standardized in their characteristic polyphenolic fractions—could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic [...] Read more.
The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke—both standardized in their characteristic polyphenolic fractions—could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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12 pages, 1023 KiB  
Article
Bergamot Polyphenolic Fraction for the Control of Flupyradifurone-Induced Poisoning in Honeybees
by Roberto Bava, Carmine Lupia, Fabio Castagna, Stefano Ruga, Saverio Nucera, Rosamaria Caminiti, Rosa Maria Bulotta, Clara Naccari, Cristina Carresi, Vincenzo Musolino, Giancarlo Statti, Domenico Britti, Vincenzo Mollace and Ernesto Palma
Animals 2024, 14(4), 608; https://doi.org/10.3390/ani14040608 - 13 Feb 2024
Cited by 2 | Viewed by 1411
Abstract
Flupyradifurone (FLU) is a butenolide insecticide that has come onto the market relatively recently. It is used in agriculture to control aphids, psyllids, and whiteflies. Toxicity studies have decreed its low toxicity to honeybees. However, recent research has challenged these claims; oral exposure [...] Read more.
Flupyradifurone (FLU) is a butenolide insecticide that has come onto the market relatively recently. It is used in agriculture to control aphids, psyllids, and whiteflies. Toxicity studies have decreed its low toxicity to honeybees. However, recent research has challenged these claims; oral exposure to the pesticide can lead to behavioral abnormalities and in the worst cases, lethal phenomena. Compounds with antioxidant activity, such as flavonoids and polyphenols, have been shown to protect against the toxic effects of pesticides. The aim of this research was to evaluate the possible protective effect of the bergamot polyphenolic fraction (BPF) against behavioral abnormalities and lethality induced by toxic doses of FLU orally administered to honeybees under laboratory conditions. Honeybees were assigned to experimental groups in which two toxic doses of FLU, 50 mg/L and 100 mg/L were administered. In other replicates, three doses (1, 2 and 5 mg/kg) of the bergamot polyphenolic fraction (BPF) were added to the above toxic doses. In the experimental groups intoxicated with FLU at the highest dose tested, all caged subjects (20 individuals) died within the second day of administration. The survival probability of the groups to which the BPF was added was compared to that of the groups to which only the toxic doses of FLU were administered. The mortality rate in the BPF groups was statistically lower (p < 0.05) than in the intoxicated groups; in addition, a lower percentage of individuals exhibited behavioral abnormalities. According to this research, the ingestion of the BPF attenuates the harmful effects of FLU. Further studies are needed before proposing BPF incorporation into the honeybees’ diet, but there already seem to be beneficial effects associated with its intake. Full article
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15 pages, 3596 KiB  
Article
The Effect of an Innovative Combination of Bergamot Polyphenolic Fraction and Cynara cardunculus L. Extract on Weight Gain Reduction and Fat Browning in Obese Mice
by Saverio Nucera, Federica Scarano, Roberta Macrì, Rocco Mollace, Micaela Gliozzi, Cristina Carresi, Stefano Ruga, Maria Serra, Annamaria Tavernese, Rosamaria Caminiti, Annarita Coppoletta, Antonio Cardamone, Tiziana Montalcini, Arturo Pujia, Ernesto Palma, Carolina Muscoli, Francesco Barillà, Vincenzo Musolino and Vincenzo Mollace
Int. J. Mol. Sci. 2024, 25(1), 191; https://doi.org/10.3390/ijms25010191 - 22 Dec 2023
Cited by 8 | Viewed by 2763
Abstract
Obesity is one of the world’s most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation [...] Read more.
Obesity is one of the world’s most serious public health issues, with a high risk of developing a wide range of diseases. As a result, focusing on adipose tissue dysfunction may help to prevent the metabolic disturbances commonly associated with obesity. Nutraceutical supplementation may be a crucial strategy for improving WAT inflammation and obesity and accelerating the browning process. The aim of this study was to perform a preclinical “proof of concept” study on Bergacyn®, an innovative formulation originating from a combination of bergamot polyphenolic fraction (BPF) and Cynara cardunculus (CyC), for the treatment of adipose tissue dysfunction. In particular, Bergacyn® supplementation in WD/SW-fed mice at doses of 50 mg/kg given orally for 12 weeks, was able to reduce body weight and total fat mass in the WD/SW mice, in association with an improvement in plasma biochemical parameters, including glycemia, total cholesterol, and LDL levels. In addition, a significant reduction in serum ALT levels was highlighted. The decreased WAT levels corresponded to an increased weight of BAT tissue, which was associated with a downregulation of PPARγ as compared to the vehicle group. Bergacyn® was able to restore PPARγ levels and prevent NF-kB overexpression in the WAT of mice fed a WD/SW diet, suggesting an improved oxidative metabolism and inflammatory status. These results were associated with a significant potentiation of the total antioxidant status in WD/SW mice. Finally, our data show, for the first time, that Bergacyn® supplementation may be a valuable approach to counteract adipose tissue dysfunction and obesity-associated effects on cardiometabolic risk. Full article
(This article belongs to the Special Issue The Effect of Food-Derived Compounds on Brown Fat Cell Function)
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13 pages, 1073 KiB  
Article
Protective Role of Bergamot Polyphenolic Fraction (BPF) against Deltamethrin Toxicity in Honeybees (Apis mellifera)
by Roberto Bava, Fabio Castagna, Stefano Ruga, Rosamaria Caminiti, Saverio Nucera, Rosa Maria Bulotta, Clara Naccari, Domenico Britti, Vincenzo Mollace and Ernesto Palma
Animals 2023, 13(24), 3764; https://doi.org/10.3390/ani13243764 - 6 Dec 2023
Cited by 5 | Viewed by 1946
Abstract
Pesticide-induced poisoning phenomena are a serious problem for beekeeping and can cause large losses of honeybee populations due to acute and sub-acute poisoning. The reduced responsiveness of honeybees to the damage caused by pesticides used in agriculture can be traced back to a [...] Read more.
Pesticide-induced poisoning phenomena are a serious problem for beekeeping and can cause large losses of honeybee populations due to acute and sub-acute poisoning. The reduced responsiveness of honeybees to the damage caused by pesticides used in agriculture can be traced back to a general qualitative and quantitative impoverishment of the nectar resources of terrestrial ecosystems. Malnutrition is associated with a decline in the functionality of the immune system and the systems that are delegated to the detoxification of the organism. This research aimed to verify whether bergamot polyphenolic extract (BPF) could have protective effects against poisoning by the pyrethroid pesticide deltamethrin. The studies were conducted with caged honeybees under controlled conditions. Sub-lethal doses of pesticides and related treatments for BPF were administered. At a dose of 21.6 mg/L, deltamethrin caused mortality in all treated subjects (20 caged honeybees) after one day of administration. The groups where BPF (1 mg/kg) was added to the toxic solution recorded the survival of honeybees by up to three days. Comparing the honeybees of the groups in which the BPF-deltamethrin association was added to the normal diet (sugar solution) with those in which deltamethrin alone was added to the normal diet, the BPF group had a statistically significant reduction in the honeybee mortality rate (p ≤ 0.05) and a greater consumption of food. Therefore, it can be argued that the inclusion of BPF and its constituent antioxidants in the honeybee diet reduces toxicity and oxidative stress caused by oral intake of deltamethrin. Furthermore, it can be argued that BPF administration could compensate for metabolic energy deficits often induced by the effects of malnutrition caused by environmental degradation and standard beekeeping practices. Full article
(This article belongs to the Special Issue Perspectives in Veterinary Toxicology and Pharmacology)
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12 pages, 1797 KiB  
Article
Beneficial Effects of Citrus Bergamia Polyphenolic Fraction on Saline Load-Induced Injury in Primary Cerebral Endothelial Cells from the Stroke-Prone Spontaneously Hypertensive Rat Model
by Rosita Stanzione, Maurizio Forte, Maria Cotugno, Francesca Oppedisano, Cristina Carresi, Simona Marchitti, Vincenzo Mollace, Massimo Volpe and Speranza Rubattu
Nutrients 2023, 15(6), 1334; https://doi.org/10.3390/nu15061334 - 9 Mar 2023
Cited by 4 | Viewed by 2199
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Dietary Supplements in Cardiovascular and Metabolic Diseases)
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19 pages, 1703 KiB  
Review
The Phytochemical Synergistic Properties of Combination of Bergamot Polyphenolic Fraction and Cynara cardunculus Extract in Non-Alcoholic Fatty Liver Disease
by Jessica Maiuolo, Rocco Mollace, Francesca Bosco, Federica Scarano, Francesca Oppedisano, Saverio Nucera, Stefano Ruga, Lorenza Guarnieri, Roberta Macri, Irene Bava, Cristina Carresi, Micaela Gliozzi, Vincenzo Musolino, Antonio Cardamone, Anna Rita Coppoletta, Andrea Barillaro, Virginia Simari, Daniela Salvemini, Ernesto Palma and Vincenzo Mollace
Agriculture 2023, 13(2), 249; https://doi.org/10.3390/agriculture13020249 - 19 Jan 2023
Cited by 4 | Viewed by 4302
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered one of the leading causes of liver-related morbidity and mortality. NAFLD is a cluster of liver disorders that includes the accumulation of fat in the liver, insulin resistance, diffuse steatosis, lobular inflammation, fibrosis, cirrhosis and, in [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is considered one of the leading causes of liver-related morbidity and mortality. NAFLD is a cluster of liver disorders that includes the accumulation of fat in the liver, insulin resistance, diffuse steatosis, lobular inflammation, fibrosis, cirrhosis and, in the latter stages, liver cancer. Due to the complexity of the disease and the multifactorial basis for the development of liver dysfunction, there is currently no unique drug treatment for NAFLD and the pharmacological options are inconclusive. In recent years, natural products have been studied for their potential beneficial effect in both preventing and treating fatty liver and its consequences in both local and systemic effects related to NAFLD. In particular, bergamot polyphenolic fraction (BPF), which is rich in natural polyphenols, and Cynara cardunculus wild type (which contains large quantities of sesquiterpenes, caffeic acid derivatives and luteolin) have both been investigated in both pre-clinical settings and clinical studies showing their effect in counteracting NAFLD-related health issues. In the present review we summarize the experimental and clinical evidence on the effect of BPF and Cynara extract alone or in their combination product (Bergacyn®) in NAFLD. In particular, data reported show that both extracts may synergize in counteracting the pathophysiological basis of NAFLD by inhibiting lipid accumulation in liver cells, oxidative stress and inflammation subsequent to liver syeatosis and, in the latter stages, liver fibrosis and tissue degeneration. Moreover, due to its powerful vasoprotective effect, the combination of BPF and Cynara extract (Bergacyn®) leads to improved endothelial dysfunction and cardioprotective response in both animal models of NAFLD, in veterinary medicine and in humans. Thus, supplementation with BPF and Cynara cardunculus extract and their combination product (Bergacyn®) represent a novel and potentially useful approach in preventing and treating NAFLD-associated complications. Full article
(This article belongs to the Special Issue Advanced Research on Bergamot (Citrus bergamia Risso & Poiteau))
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13 pages, 1059 KiB  
Article
Citrus Bergamia and Cynara Cardunculus Reduce Serum Uric Acid in Individuals with Non-Alcoholic Fatty Liver Disease
by Yvelise Ferro, Samantha Maurotti, Elisa Mazza, Roberta Pujia, Angela Sciacqua, Vincenzo Musolino, Vincenzo Mollace, Arturo Pujia and Tiziana Montalcini
Medicina 2022, 58(12), 1728; https://doi.org/10.3390/medicina58121728 - 26 Nov 2022
Cited by 12 | Viewed by 3906
Abstract
Background and Objectives: Hyperuricemia and liver steatosis are risk factors for cardiovascular diseases and mortality. The use of natural compounds could be a safe and effective alternative to drugs for the treatment of fatty liver and hyperuricemia. Polyphenolic fraction of Citrus Bergamia in [...] Read more.
Background and Objectives: Hyperuricemia and liver steatosis are risk factors for cardiovascular diseases and mortality. The use of natural compounds could be a safe and effective alternative to drugs for the treatment of fatty liver and hyperuricemia. Polyphenolic fraction of Citrus Bergamia in association with the extract of Cynara Cardunculus, as nutraceutical, is able to reduce body weight, hepatic steatosis and markers of oxidative stress. Then, we performed a secondary analysis of a double-blind placebo-controlled trial to examine the effects of this nutraceutical on serum uric acid levels in adults with fatty liver. Materials and Methods: The study included 94 individuals with hepatic steatosis. For six weeks, the intervention group was given a nutraceutical (300 mg/day) comprising a Bergamot polyphenol fraction and Cynara Cardunculus extract. The control group received a daily pill of placebo. Serum uric acid, lipids, glucose and anthropometric parameters were assessed at baseline and after 6 weeks. Results: We found a greater reduction in serum uric acid in the participants taking the nutraceutical rather than placebo (−0.1 ± 0.7 mg/dL vs. 0.3 ± 0.7 mg/dL, p = 0.004), and especially in those with moderate/severe hepatic steatosis also after adjustment for confounding variables. In addition, we analysed the two groups according to tertiles of uric acid concentration. Among participants taking the nutraceutical, we found in those with the highest baseline serum uric acid (>5.4 mg/dL) the greater reduction compared to the lowest baseline uric acid (−7.8% vs. +4.9%; adjusted p = 0.04). The stepwise multivariable analysis confirmed the association between the absolute serum uric acid change and nutraceutical treatment (B = −0.43; p = 0.004). Conclusions: A nutraceutical containing bioactive components from bergamot and wild cardoon reduced serum uric acid during 6 weeks in adults with fatty liver. Future investigations are needed to evaluate the efficacy of this nutraceutical in the treatment of hyperuricaemia. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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11 pages, 2040 KiB  
Article
Bergamot Polyphenol Extract Reduces Hepatocyte Neutral Fat by Increasing Beta-Oxidation
by Angela Mirarchi, Rosario Mare, Vincenzo Musolino, Saverio Nucera, Vincenzo Mollace, Arturo Pujia, Tiziana Montalcini, Stefano Romeo and Samantha Maurotti
Nutrients 2022, 14(16), 3434; https://doi.org/10.3390/nu14163434 - 20 Aug 2022
Cited by 21 | Viewed by 4017
Abstract
Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material [...] Read more.
Background: Bergamot polyphenolic fraction (PF) extract exerts a beneficial against liver steatosis. However, the fundamental processes underlying this beneficial effect of bergamot PF remain elusive. In this work, we examined the effect of bergamot PF extract on 2D and 3D hepatocyte cultures. Material and Methods: We evaluated the effect of bergamot PF in 2D and 3D cultures from rat, human hepatoma cells, and human primary hepatocytes. Results: In 2D cell culture, we demonstrated that incubation with bergamot PF decreases intracellular lipid content and is associated with an increase in expression levels of ß-oxidation genes (Acox1, Pparα, and Ucp2) and lipophagy (Atg7). Moreover, we confirm this effect on 3D spheroids and organoids. Conclusion: Incubation with bergamot PF reduces intracellular lipid neutral fat potentially by increasing intracellular pathways related to beta-oxidation. Full article
(This article belongs to the Special Issue Adiposity, Diabetes and Metabolic Diseases)
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11 pages, 1796 KiB  
Communication
The Impairment of Cell Metabolism by Cardiovascular Toxicity of Doxorubicin Is Reversed by Bergamot Polyphenolic Fraction Treatment in Endothelial Cells
by Cristina Algieri, Chiara Bernardini, Francesca Oppedisano, Debora La Mantia, Fabiana Trombetti, Ernesto Palma, Monica Forni, Vincenzo Mollace, Giovanni Romeo, Ilaria Troisio and Salvatore Nesci
Int. J. Mol. Sci. 2022, 23(16), 8977; https://doi.org/10.3390/ijms23168977 - 11 Aug 2022
Cited by 17 | Viewed by 2204
Abstract
The beneficial effects of bergamot polyphenolic fraction (BPF) on the mitochondrial bioenergetics of porcine aortic endothelial cells (pAECs) were verified under the cardiotoxic action of doxorubicin (DOX). The cell viability of pAECs treated for 24 h with different concentrations of DOX was reduced [...] Read more.
The beneficial effects of bergamot polyphenolic fraction (BPF) on the mitochondrial bioenergetics of porcine aortic endothelial cells (pAECs) were verified under the cardiotoxic action of doxorubicin (DOX). The cell viability of pAECs treated for 24 h with different concentrations of DOX was reduced by 50%, but the negative effect of DOX was reversed in the presence of increasing doses of BPF (100 µg/mL and 200 µg/mL BPF). An analysis of the protective effect of BPF on the toxic action of DOX was also carried out on cell respiration. We observed the inhibition of the mitochondrial activity at 10 µM DOX, which was not restored by 200 µg/mL BPF. Conversely, the decrease in basal respiration and ATP production caused by 0.5 or 1.0 µM DOX were improved in the presence of 100 or 200 µg/mL BPF, respectively. After 24 h of cell recovery with 100 µg/mL or 200 µg/mL BPF on pAECs treated with 0.5 µM or 1.0 µM DOX, respectively, the mitochondrial parameters of oxidative metabolism impaired by DOX were re-boosted. Full article
(This article belongs to the Special Issue Cell Metabolism and Small Natural Compounds)
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11 pages, 823 KiB  
Article
Effect of Dietary Supplementation with Eufortyn® Colesterolo Plus on Serum Lipids, Endothelial Reactivity, Indexes of Non-Alcoholic Fatty Liver Disease and Systemic Inflammation in Healthy Subjects with Polygenic Hypercholesterolemia: The ANEMONE Study
by Federica Fogacci, Elisabetta Rizzoli, Marina Giovannini, Marilisa Bove, Sergio D’Addato, Claudio Borghi and Arrigo F. G. Cicero
Nutrients 2022, 14(10), 2099; https://doi.org/10.3390/nu14102099 - 18 May 2022
Cited by 21 | Viewed by 4891
Abstract
We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard®), artichoke extract (Pycrinil®), artichoke dry extract. (Cynara scolymus L.), Q10 phytosome(Ubiqosome®) and zinc, could [...] Read more.
We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard®), artichoke extract (Pycrinil®), artichoke dry extract. (Cynara scolymus L.), Q10 phytosome(Ubiqosome®) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia. Participants were adhering to a low-fat, low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 1 pill each day of either Eufortyn® Colesterolo Plus or placebo. Dietary supplementation with Eufortyn® Colesterolo Plus was associated with significant improvement in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP) and endothelial reactivity (ER) in comparison with baseline, and with significant reductions in waist circumference, TC, LDL-C, LDL-C/HDL-C, lipid accumulation product and fatty liver index compared to placebo. The study shows that dietary supplementation with standardized bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome and zinc safely exerts significant improvements in serum lipids, systemic inflammation, indexes of NAFLD and endothelial reactivity in healthy subjects with moderate hypercholesterolemia. Full article
(This article belongs to the Special Issue Dietary Supplements in Cardiovascular and Metabolic Diseases)
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15 pages, 1899 KiB  
Article
Mitochondria Bioenergetic Functions and Cell Metabolism Are Modulated by the Bergamot Polyphenolic Fraction
by Cristina Algieri, Chiara Bernardini, Francesca Oppedisano, Debora La Mantia, Fabiana Trombetti, Ernesto Palma, Monica Forni, Vincenzo Mollace, Giovanni Romeo and Salvatore Nesci
Cells 2022, 11(9), 1401; https://doi.org/10.3390/cells11091401 - 20 Apr 2022
Cited by 16 | Viewed by 3268
Abstract
The bergamot polyphenolic fraction (BPF) was evaluated in the F1FO-ATPase activity of swine heart mitochondria. In the presence of a concentration higher than 50 µg/mL BPF, the ATPase activity of F1FO-ATPase, dependent on the natural [...] Read more.
The bergamot polyphenolic fraction (BPF) was evaluated in the F1FO-ATPase activity of swine heart mitochondria. In the presence of a concentration higher than 50 µg/mL BPF, the ATPase activity of F1FO-ATPase, dependent on the natural cofactor Mg2+, increased by 15%, whereas the enzyme activity in the presence of Ca2+ was inhibited by 10%. By considering this opposite BPF effect, the F1FO-ATPase activity involved in providing ATP synthesis in oxidative phosphorylation and triggering mitochondrial permeability transition pore (mPTP) formation has been evaluated. The BPF improved the catalytic coupling of oxidative phosphorylation in the presence of a substrate at the first phosphorylation site, boosting the respiratory control ratios (state 3/state 4) by 25% and 85% with 50 µg/mL and 100 µg/mL BPF, respectively. Conversely, the substrate at the second phosphorylation site led to the improvement of the state 3/state 4 ratios by 15% only with 100 µg/mL BPF. Moreover, the BPF carried out its beneficial effect on the mPTP phenomenon by desensitizing the pore opening. The acute effect of the BPF on the metabolism of porcine aortica endothelial cells (pAECs) showed an ATP rate index greater than one, which points out a prevailing mitochondrial oxidative metabolism with respect to the glycolytic pathway, and this ratio rose by about three times with 100 µg/mL BPF. Consistently, the mitochondrial ATP turnover, in addition to the basal and maximal respiration, were higher in the presence of the BPF than in the controls, and the MTT test revealed an increase in cell viability with a BPF concentration above 200 µg/mL. Therefore, the molecule mixture of the BPF aims to ensure good performance of the mitochondrial bioenergetic parameters. Full article
(This article belongs to the Special Issue Recent Advances in Metabolism and Oxidative Stress in Human Diseases)
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