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Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation
INTRODUCTION: Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481966/ https://www.ncbi.nlm.nih.gov/pubmed/37680900 http://dx.doi.org/10.3389/fnut.2023.1201007 |
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author | Janilkarn-Urena, Isis Idrissova, Alina Zhang, Mindy VanDreal, Masha Sanghavi, Neysa Skinner, Samantha G. Cheng, Sydney Zhang, Zeyu Watanabe, Junji Asatryan, Liana Cadenas, Enrique Davies, Daryl L. |
author_facet | Janilkarn-Urena, Isis Idrissova, Alina Zhang, Mindy VanDreal, Masha Sanghavi, Neysa Skinner, Samantha G. Cheng, Sydney Zhang, Zeyu Watanabe, Junji Asatryan, Liana Cadenas, Enrique Davies, Daryl L. |
author_sort | Janilkarn-Urena, Isis |
collection | PubMed |
description | INTRODUCTION: Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity. METHODS: Female c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant. RESULTS: Dihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17. DISCUSSION: Dihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology. |
format | Online Article Text |
id | pubmed-10481966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104819662023-09-07 Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation Janilkarn-Urena, Isis Idrissova, Alina Zhang, Mindy VanDreal, Masha Sanghavi, Neysa Skinner, Samantha G. Cheng, Sydney Zhang, Zeyu Watanabe, Junji Asatryan, Liana Cadenas, Enrique Davies, Daryl L. Front Nutr Nutrition INTRODUCTION: Excessive alcohol consumption leads to a myriad of detrimental health effects, including alcohol-associated liver disease (ALD). Unfortunately, no available treatments exist to combat the progression of ALD beyond corticosteroid administration and/or liver transplants. Dihydromyricetin (DHM) is a bioactive polyphenol and flavonoid that has traditionally been used in Chinese herbal medicine for its robust antioxidant and anti-inflammatory properties. It is derived from many plants, including Hovenia dulcis and is found as the active ingredient in a variety of popular hangover remedies. Investigations utilizing DHM have demonstrated its ability to alleviate ethanol-induced disruptions in mitochondrial and lipid metabolism, while demonstrating hepatoprotective activity. METHODS: Female c57BL/6J mice (n = 12/group) were treated using the Lieber DeCarli forced-drinking and ethanol (EtOH) containing liquid diet, for 5 weeks. Mice were randomly divided into three groups: (1) No-EtOH, (2) EtOH [5% (v/v)], and (3) EtOH [5% (v/v)] + DHM (6 mg/mL). Mice were exposed to ethanol for 2 weeks to ensure the development of ALD pathology prior to receiving dihydromyricetin supplementation. Statistical analysis included one-way ANOVA along with Bonferroni multiple comparison tests, where p ≤ 0.05 was considered statistically significant. RESULTS: Dihydromyricetin administration significantly improved aminotransferase levels (AST/ALT) and reduced levels of circulating lipids including LDL/VLDL, total cholesterol (free cholesterol), and triglycerides. DHM demonstrated enhanced lipid clearance by way of increased lipophagy activity, shown as the increased interaction and colocalization of p62/SQSTM-1, LC3B, and PLIN-1 proteins. DHM-fed mice had increased hepatocyte-to-hepatocyte lipid droplet (LD) heterogeneity, suggesting increased neutralization and sequestration of free lipids into LDs. DHM administration significantly reduced prominent pro-inflammatory cytokines commonly associated with ALD pathology such as TNF-α, IL-6, and IL-17. DISCUSSION: Dihydromyricetin is commercially available as a dietary supplement. The results of this proof-of-concept study demonstrate its potential utility and functionality as a cost-effective and safe candidate to combat inflammation and the progression of ALD pathology. Frontiers Media S.A. 2023-08-23 /pmc/articles/PMC10481966/ /pubmed/37680900 http://dx.doi.org/10.3389/fnut.2023.1201007 Text en Copyright © 2023 Janilkarn-Urena, Idrissova, Zhang, VanDreal, Sanghavi, Skinner, Cheng, Zhang, Watanabe, Asatryan, Cadenas and Davies. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Nutrition Janilkarn-Urena, Isis Idrissova, Alina Zhang, Mindy VanDreal, Masha Sanghavi, Neysa Skinner, Samantha G. Cheng, Sydney Zhang, Zeyu Watanabe, Junji Asatryan, Liana Cadenas, Enrique Davies, Daryl L. Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title | Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title_full | Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title_fullStr | Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title_full_unstemmed | Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title_short | Dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
title_sort | dihydromyricetin supplementation improves ethanol-induced lipid accumulation and inflammation |
topic | Nutrition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481966/ https://www.ncbi.nlm.nih.gov/pubmed/37680900 http://dx.doi.org/10.3389/fnut.2023.1201007 |
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