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Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease
There is a need for continued drug development for nonalcoholic steatohepatitis (NASH). Bergamot is a plant whose fruit juice is enriched with flavonoids and phenolic compounds which improves dyslipidemia and markers of systemic inflammation in patients with Metabolic Syndrome. The aim of this study...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018973/ https://www.ncbi.nlm.nih.gov/pubmed/32054943 http://dx.doi.org/10.1038/s41598-020-59485-3 |
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author | Musolino, Vincenzo Gliozzi, Micaela Scarano, Federica Bosco, Francesca Scicchitano, Miriam Nucera, Saverio Carresi, Cristina Ruga, Stefano Zito, Maria Caterina Maiuolo, Jessica Macrì, Roberta Amodio, Nicola Juli, Giada Tassone, Pierfrancesco Mollace, Rocco Caffrey, Rebecca Marioneaux, Jonathon Walker, Ross Ehrlich, James Palma, Ernesto Muscoli, Carolina Bedossa, Pierre Salvemini, Daniela Mollace, Vincenzo Sanyal, Arun J. |
author_facet | Musolino, Vincenzo Gliozzi, Micaela Scarano, Federica Bosco, Francesca Scicchitano, Miriam Nucera, Saverio Carresi, Cristina Ruga, Stefano Zito, Maria Caterina Maiuolo, Jessica Macrì, Roberta Amodio, Nicola Juli, Giada Tassone, Pierfrancesco Mollace, Rocco Caffrey, Rebecca Marioneaux, Jonathon Walker, Ross Ehrlich, James Palma, Ernesto Muscoli, Carolina Bedossa, Pierre Salvemini, Daniela Mollace, Vincenzo Sanyal, Arun J. |
author_sort | Musolino, Vincenzo |
collection | PubMed |
description | There is a need for continued drug development for nonalcoholic steatohepatitis (NASH). Bergamot is a plant whose fruit juice is enriched with flavonoids and phenolic compounds which improves dyslipidemia and markers of systemic inflammation in patients with Metabolic Syndrome. The aim of this study was to perform a preclinical “proof of concept” study of Bergamot polyphenolic formulation (BPF99) for the treatment of NASH. A disease reversal study was performed in the diet-induced animal model of NAFLD (DIAMOND). Groups of 8 weeks old mice were randomly assigned to receive chow diet, high fat diet with sugar in drinking water (Western diet- WD). Mice on WD were further randomized to continue on WD gavaged with vehicle or continue on WD with additional gavage of BPF99 (50 mg/kg) after 16 weeks of diet. Mice were euthanized after 11 additional weeks. The primary endpoint was resolution of NASH. Secondary endpoints included changes in individual histological features, body weight, liver enzymes, dyslipidemia, markers of oxidative stress and molecular markers of disease activity and fibrosis. The results showed that BPF99 reduced ALT (mean 71.6 vs 44.6 IU/l, p < 0.01), triglycerides (38.8 vs 28.1 mg/dl, p < 0.05), LDL-C (39.2 vs 23.7 mg/dl, p < 0.001). It significantly improved NASH resolution (p < 0.001) and the SAF scores (p < 0.05) while the NAS improvement approached significance. BPF99 reduced markers of oxidative stress, along with reduced JNK and p38 MAP kinase activity. BPF99 did not reduce the number of mice with fibrosis but improved collagen proportional area (p < 0.04) and procollagen I and III expression. Collectively our results showed that BPF99 resolves NASH and ameliorates key histological and pathophysiological features of NASH along with improvement in ALT and dyslipidemia in the DIAMOND mice. |
format | Online Article Text |
id | pubmed-7018973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70189732020-02-21 Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease Musolino, Vincenzo Gliozzi, Micaela Scarano, Federica Bosco, Francesca Scicchitano, Miriam Nucera, Saverio Carresi, Cristina Ruga, Stefano Zito, Maria Caterina Maiuolo, Jessica Macrì, Roberta Amodio, Nicola Juli, Giada Tassone, Pierfrancesco Mollace, Rocco Caffrey, Rebecca Marioneaux, Jonathon Walker, Ross Ehrlich, James Palma, Ernesto Muscoli, Carolina Bedossa, Pierre Salvemini, Daniela Mollace, Vincenzo Sanyal, Arun J. Sci Rep Article There is a need for continued drug development for nonalcoholic steatohepatitis (NASH). Bergamot is a plant whose fruit juice is enriched with flavonoids and phenolic compounds which improves dyslipidemia and markers of systemic inflammation in patients with Metabolic Syndrome. The aim of this study was to perform a preclinical “proof of concept” study of Bergamot polyphenolic formulation (BPF99) for the treatment of NASH. A disease reversal study was performed in the diet-induced animal model of NAFLD (DIAMOND). Groups of 8 weeks old mice were randomly assigned to receive chow diet, high fat diet with sugar in drinking water (Western diet- WD). Mice on WD were further randomized to continue on WD gavaged with vehicle or continue on WD with additional gavage of BPF99 (50 mg/kg) after 16 weeks of diet. Mice were euthanized after 11 additional weeks. The primary endpoint was resolution of NASH. Secondary endpoints included changes in individual histological features, body weight, liver enzymes, dyslipidemia, markers of oxidative stress and molecular markers of disease activity and fibrosis. The results showed that BPF99 reduced ALT (mean 71.6 vs 44.6 IU/l, p < 0.01), triglycerides (38.8 vs 28.1 mg/dl, p < 0.05), LDL-C (39.2 vs 23.7 mg/dl, p < 0.001). It significantly improved NASH resolution (p < 0.001) and the SAF scores (p < 0.05) while the NAS improvement approached significance. BPF99 reduced markers of oxidative stress, along with reduced JNK and p38 MAP kinase activity. BPF99 did not reduce the number of mice with fibrosis but improved collagen proportional area (p < 0.04) and procollagen I and III expression. Collectively our results showed that BPF99 resolves NASH and ameliorates key histological and pathophysiological features of NASH along with improvement in ALT and dyslipidemia in the DIAMOND mice. Nature Publishing Group UK 2020-02-13 /pmc/articles/PMC7018973/ /pubmed/32054943 http://dx.doi.org/10.1038/s41598-020-59485-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Musolino, Vincenzo Gliozzi, Micaela Scarano, Federica Bosco, Francesca Scicchitano, Miriam Nucera, Saverio Carresi, Cristina Ruga, Stefano Zito, Maria Caterina Maiuolo, Jessica Macrì, Roberta Amodio, Nicola Juli, Giada Tassone, Pierfrancesco Mollace, Rocco Caffrey, Rebecca Marioneaux, Jonathon Walker, Ross Ehrlich, James Palma, Ernesto Muscoli, Carolina Bedossa, Pierre Salvemini, Daniela Mollace, Vincenzo Sanyal, Arun J. Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title | Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title_full | Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title_fullStr | Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title_full_unstemmed | Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title_short | Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease |
title_sort | bergamot polyphenols improve dyslipidemia and pathophysiological features in a mouse model of non-alcoholic fatty liver disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018973/ https://www.ncbi.nlm.nih.gov/pubmed/32054943 http://dx.doi.org/10.1038/s41598-020-59485-3 |
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