Bergamot (Citrus bergamia) is a fragrant citrus fruit the size of an orange, with a yellow or green color similar to a lime, depending on ripeness. Although native to South‐East Asia, 80% of bergamot is produced in Calabria, southern Italy, where it grows extensively. Bergamot is known to have a high amount of flavonoids and flavonoid glycosides such as: neoeriocitrin, neohesperidin, naringin, rutin, neodesmin, rhoifolin, and poncirin (with particularly high concentrations of naringin and neohesperidin).
- Antiinflammatory: Bergamot flavonoid reduces lipopolysaccharide-induced inflammatory response in THP-1 monocytes, through SIRT1-mediated nuclear factor-κB inhibition.
- Appetite Control: Bergamot contains polysaccharides and a fibrous‐woody fraction that can be used in food integrators and in dietary products in order to reduce the sensation of hunger.
- The flavonoid fraction is able to reduce protein levels of pro‐inflammatory cytokines.
- Cytoprotective: Bergamot Juice extract has cytoprotective ability against oxidants, such as hydrogen peroxide and Iron(III) sulfate, that cause oxidative cell damage.
- Neuroprotective: The mechanisms by which the flavonoids in Bergamot exert their neuroprotective activities are associated with the modulation of specific antioxidant enzymes (antioxidant capacity), antiapoptotic activity, induction of neurotrophic factors, and modulation of different signaling pathways that influence neuronal survival, differentiation, proliferation, and apoptosis.
- Neurotransmitters: Bergamot Essential Oil (BEO) contains unidentified monoterpene hydrocarbons able to enhance the levels of amino acid neurotransmitters (glycine, aspartate, GABA, taurine, and glutamate) in the hippocampus (of rats).
- Memory: Bergamot contains a high amount of the flavonoids naringin and neohesperidin. Naringin and neohesperidin have been reported to improve learning and memory.
- Weight Loss: Bergamot polyphenolic fraction (BPF) administration resulted in a statistically significant reduction of body weight and in a trend for body mass index decrease.
- Blood Sugar: 500/1000 mg/day of Bergamot Extract shows promising data for glucose control.
- Daily supplementation of 500 mg for 30 days, BPF resulted in a significant reduction on blood glucose levels compared to baseline.
- Bone Health: Bergamot essential oil (BEO, 10 mg/kg or 20 mg/kg daily for 20 weeks) increases bone volume.
- Skin Health: Bergamot essential oil increases skin collagen content.
- Hair Health: Bergamot essential oil promotes hair growth.
- Lipid‐lowering: The lipid‐lowering effect was associated with significant reductions in biomarkers used to detect vascular oxidative damage (such as malondialdehyde, oxyLDL receptor LOX‐1, and protein kinase B (PKB)), suggesting a multi‐action improved potential for bergamot in patients taking statins.
- Metabolism: Bergamot initiates adenosine monophosphate (AMP)‐activated PK (AMPK), a central regulator of energy, and thus is involved in glucose and fatty acid metabolism.
- Cardioprotective: The lipid and glycemic lowering effects of bergamot may result in a reduction of Cardiovascular Disease risk.
- Studies suggest a cardioprotective effect of a single daily dose for 6 months of BE (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin, and 37% of naringin).
- Endothelial Health: Bergamot protects against free radical damage in the body, including the vascular endothelium, an important determinant of Cardiovascular health.
- Wound Healing: Bergamot oil and its major active components, namely limonene, linalyl acetate, and linalool, have demonstrated anti‐inflammatory, immunomodulatory, and wound healing activities.
Disease / Symptom Treatment
- Cognitive Impairment: Bergamot is characterized by a high amount of flavonoids and flavonoid glycosides, particularly naringin and neohesperidin. Naringin and neohesperidin have been reported to attenuate cognitive impairment and behavioral deficits.
- Schizophrenia: Bergamot polyphenolic fraction (BPF) supplementation significantly improved cognitive outcome in schizophrenia. Bergamot polyphenolic fraction may be proposed as a potential supplementation strategy to address cognitive dysfunctions in schizophrenia.
- Executive Cognition Functioning: Bergamot polyphenolic fraction (BPF) administration was associated with a substantial improvement of cognitive executive functioning.
- Attention: Bergamot polyphenolic fraction (BPF) administration was associated with a positive trend toward improvement in attentional resistance to interference stimuli.
- Cystic fibrosis: is a disease characterized by extensive lung inflammation. The extracts obtained from bergamot epicarps (the outermost layer of the fruit) contain components displaying strong inhibitory activity on lung inflammation.
- Antiinflammatory: The most active molecules identified from the extract of bergamot skin were bergapten and citropten. They are most likely responsible for the strong inhibitory effect on pro-inflammatory cytokines and chemokines.
- Obesity: Bergamot polyphenolic fraction (BPF), at the daily dose of 1000 mg for 30 days, could be an effective and safe agent to prevent weight gain.
- Hyperlipidemia: Bergamot‐derived extract (BE) exerts positive effects on hyperlipidemia with an oral dose from 150 mg to 1000 mg/day of flavonoids administered from 30 to 180 days, demonstrating an effect on body weight and in modulating total cholesterol, triglycerides, LDL, and HDL.
- Plaque psoriasis: Bergamot essential oil decreases psoriatic plaques (Plaque psoriasis is the most common form of the disease and appears as raised, red patches covered with a silvery white buildup of dead skin cells or scale. These patches or plaques most often appear on the scalp, knees, elbows and lower back).
Title: Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia: Data From an 8-Week, Open-Label Pilot Study
Author(s): Bruno, Antonio MD, PhD; Pandolfo, Gianluca MD, PhD; Crucitti, Manuela MD; Cedro, Clemente MD, PhD; Zoccali, Rocco Antonio MD; Muscatello, Maria Rosaria Anna MD, PhD
Institution(s): Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
Publication: Journal of Clinical Psychopharmacology
Date: August 2017
Abstract: Background Novel treatment strategies for cognitive dysfunctions may prevent long-term disability in patients with schizophrenia, and polyphenolic compounds might be a promising strategy. Bergamot (Citrus bergamia), a citrus fruit characterized by a high amount of flavonoids and flavonoid glycosides, may represent a potential nutraceutical approach to cognitive dysfunction. The present study was aimed to explore the efficacy of bergamot polyphenolic fraction (BPF) supplementation on cognitive/executive functioning in a sample of patients with schizophrenia receiving second-generation antipsychotics. Methods: Twenty outpatients treated with second-generation antipsychotics assumed BPF at an oral daily dose of 1000 mg/d for 8 weeks. Brief Psychiatric Rating Scale, Wisconsin Card Sorting Test (WCST), Verbal Fluency Task-Controlled Oral Word Association Test, and Stroop Color-Word Test were administered. Results: At end point, (week 8) BPF supplementation significantly improved WCST “perseverative errors” (P = 0.004) and semantic fluency test (P = 0.004). Moreover, a trend for other cognitive variable (WCST “categories,” phonemic fluency, and Stroop Color-Word Test) improvement was observed. Conclusions: The findings provide evidence that BPF administration may be proposed as a potential supplementation 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 patients with schizophrenia.
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Title: Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations
Author(s): Simone Perna Daniele Spadaccini Leonardo Botteri Carolina Girometta Antonella Riva Pietro Allegrini Giovanna Petrangolini Vittoria Infantino Mariangela Rondanelli
Institution(s): Department of Earth and Environmental Sciences, Mycology and Plant Pathology Laboratory, Pavia, Italy; Department of Biology, College of Science, University of Bahrain, Zallaq, Bahrain; Research and Development Unit, Indena, Milan, Italy; Department of Public Health, Experimental and Forensic Medicine, Section of Human Nutrition, Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona, University of Pavia, Pavia, Italy IRCCS Mondino Foundation, Pavia, Italy
Publication: Food Science & Nutrition
Date: January 2019
Abstract: We summarize the effects of bergamot (extract, juice, essential oil, and polyphenolic fraction) on cardiovascular, bone, inflammatory, skin diseases, mood alteration, anxiety, pain, and stress. This review included a total of 31 studies (20 studies on humans with 1709 subjects and 11 in animals (rats and mice)). In humans, bergamot‐derived extract (BE) exerts positive effects on hyperlipidemia with an oral dose from 150 mg to 1000 mg/day of flavonoids administered from 30 to 180 days, demonstrating an effect on body weight and in modulating total cholesterol, triglycerides, LDL, and HDL. Studies in animals confirm promising data on glucose control (500/1000 mg/day of BE with a treatment lasting 30 days) are available in rats. In animals models, bergamot essential oil (BEO, 10 mg/kg or 20 mg/kg daily for 20 weeks) increases bone volume, decreases psoriatic plaques, increases skin collagen content, and promotes hair growth. Bergamot juice (20 mg/kg) is promising in terms of pro‐inflammatory cytokine reduction. In humans, aromatherapy (from 15 to 30 min) does not appear to be useful in order to reduce stress, anxiety, and nausea, compared to placebo. Compared to baseline, BE topical application and BEO aromatherapy reduce blood diastolic and systolic pressure and could have a significant effect on improving mental conditions.
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Title: The essential oil of bergamot enhances the levels of amino acid neurotransmitters in the hippocampus of rat: Implication of monoterpene hydrocarbons
Author(s): Luigi A. Morrone, Laura Rombolà, Cinzia Pelle, Maria T. Corasaniti, Simona Zappettini, Paolo Paudice, Giambattista Bonanno, Giacinto Bagetta
Institution(s): Department of Pharmacobiology and University Center for Adaptive Disorders and Headache (UCHAD), section of Neuropharmacology of Normal and Pathological Neuronal Plasticity, University of Calabria, Arcavacata di Rende (CS), Italy; Department of Pharmacobiological Sciences, University of Catanzaro “Magna Graecia”, Catanzaro, Italy; Experimental Neurobiology Center, “Mondino-Tor Vergata”, University of Rome Tor Vergata, Rome, Italy; Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, Genoa, Italy
Publication: Pharmacological Research
Date: April 2007
Abstract: The effects of bergamot essential oil (BEO) on the release of amino acid neurotransmitters in rat hippocampus have been studied by in vivo microdialysis and by in vitro superfusion of isolated nerve terminals. Intraperitoneal administration of BEO (100 μl/kg) significantly elevated the extracellular concentration of aspartate, glycine and taurine in a Ca2+-dependent manner. A dose-relation study generated a bell-shaped curve. When perfused into the hippocampus via the dialysis probe (20 μl/20 min), BEO produced a significant increase of extracellular aspartate, glycine, taurine as well as of GABA and glutamate. The augmentation of all amino acids was Ca2+-independent. Focally injected 1:1 diluted BEO preferentially caused extracellular increase of glutamate. Interestingly, this release appeared to be strictly Ca2+-dependent. BEO concentration-dependently enhanced the release of [3H]d-aspartate from superfused hippocampal synaptosomes. Similar results were obtained by monitoring the BEO-evoked release of endogenous glutamate. At relatively high concentrations, the BEO-induced [3H]d-aspartate release was almost entirely prevented by the glutamate transporter blocker dl-threo-β-benzyloxyaspartic acid (dl-TBOA) and was Ca2+-independent. At relatively low concentrations the release of [3H]d-aspartate was only in part (∼50%) dl-TBOA-sensitive and Ca2+-independent; the remaining portion of release was dependent on extracellular Ca2+. Interestingly, the monoterpene hydrocarbon-free fraction of the essential oil appeared to be inactive while the bergapten-free fraction superimposed the releasing effect of BEO supporting the deduction that psoralens may not be implicated. To conclude, BEO contains into its volatile fraction still unidentified monoterpene hydrocarbons able to stimulate glutamate release by transporter reversal and/or by exocytosis, depending on the dose administered.
Title: Metabolic outcomes of bergamot polyphenolic fraction administration in patients treated with second-generation antipsychotics: a pilot study
Author(s): Antonio Bruno, Gianluca Pandolfo, Manuela Crucitti, Antonino Maisano, Rocco A. Zoccali, Maria Rosaria Anna Muscatello
Institution(s): Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, 1, Messina, Italy
Publication: The Journal of Nutritional Biochemistry
Date: October 2016
Abstract: 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.
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Title: Bergamot (Citrus bergamia Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines
Author(s): Monica Borgatti, Irene Mancini, Nicoletta Bianchi, Alessandra Guerrini, Ilaria Lampronti, Damiano Rossi, Gianni Sacchetti, Roberto Gambari
Institution(s): Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara 74, Ferrara, 44121, Italy
Publication: BMC Biochemistry
Date: April 2011
Abstract: Background: Cystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (Citrus bergamia Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology. Methods: The extracts were chemically characterized by 1H-NMR (nuclear magnetic resonance), GC-FID (gas chromatography-flame ionization detector), GC-MS (gas chromatography-mass spectrometry) and HPLC (high pressure liquid chromatography). Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a) cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b) accumulation of IL-8 mRNA by real-time PCR. Results: The extracts obtained from bergamot (Citrus bergamia Risso) epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated Pseudomonas aeruginosa. Conclusions: These obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.
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