Bergamot Polyphenolic Fraction Supplementation Improves Cognitive Functioning in Schizophrenia. Data From an 8-Week, Open-
Label Pilot Study

Journal of Clinical Psychopharmacology: August 2017 – Volume 37 – Issue 4 – p 468-471
Antonio Bruno, MD, PhD, Gianluca Pandolfo, MD, PhD, Manuela Crucitti, MD, Clemente Cedro, MD, PhD,
Rocco Antonio Zoccali, MD, and Maria Rosaria Anna Muscatello, MD, PhD

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.

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.

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.

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.

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

Advances in Biological Chemistry Jan 2014
Micaela Gliozzi, Cristina Carresi, Vincenzo Musolino, Ernesto Palma, Carolina Muscoli, Cristiana Vitale, Santo Gratteri, Giuseppe Muscianisi, Elzbieta Janda, Saverio Muscoli, Francesco Romeo, Salvatore Ragusa, Rocco Mollace, Ross Walker, James Ehrlich, Vincenzo Mollace*

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 Polyphenols Boost Therapeutic Effects of the Diet on Non-Alcoholic Steatohepatitis (NASH) Induced by “Junk Food”: Evidence for Anti-Inflammatory Activity

Nutrients Nov 2018. Maddalena Parafati, Antonella Lascala, Daniele La Russa, Chiara Mignogna, Francesca Trimboli, Valeria Maria Morittu, Concetta Riillo, Rachele Macirella, Vincenzo Mollace, Elvira Brunelli and Elzbieta Janda

Wrong alimentary behaviors and so-called “junk food” are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The “junk food” toxicity can be studied in “cafeteria” (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.

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