Cargando…
Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis
The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcino...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865844/ https://www.ncbi.nlm.nih.gov/pubmed/36678220 http://dx.doi.org/10.3390/nu15020350 |
_version_ | 1784875940110663680 |
---|---|
author | Inoue, Takayuki Fu, Bin Nishio, Miwako Tanaka, Miyako Kato, Hisashi Tanaka, Masashi Itoh, Michiko Yamakage, Hajime Ochi, Kozue Ito, Ayaka Shiraki, Yukihiro Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Inoue, Shian Saeki, Kumiko Enomoto, Atsushi Suganami, Takayoshi Satoh-Asahara, Noriko |
author_facet | Inoue, Takayuki Fu, Bin Nishio, Miwako Tanaka, Miyako Kato, Hisashi Tanaka, Masashi Itoh, Michiko Yamakage, Hajime Ochi, Kozue Ito, Ayaka Shiraki, Yukihiro Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Inoue, Shian Saeki, Kumiko Enomoto, Atsushi Suganami, Takayoshi Satoh-Asahara, Noriko |
author_sort | Inoue, Takayuki |
collection | PubMed |
description | The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcinoma. Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid with antioxidant and anti-inflammatory properties commonly found in various foods and health supplement products. In this study, we demonstrated that Taxifolin treatment markedly prevented the development of hepatic steatosis, chronic inflammation, and liver fibrosis in a murine model of NASH. Its mechanisms include a direct action on hepatocytes to inhibit lipid accumulation. Taxifolin also increased brown adipose tissue activity and suppressed body weight gain through at least two distinct pathways: direct action on brown adipocytes and indirect action via fibroblast growth factor 21 production in the liver. Notably, the Taxifolin treatment after NASH development could effectively prevent the development of liver tumors. Collectively, this study provides evidence that Taxifolin shows pleiotropic effects for the treatment of the NASH continuum. Our data also provide insight into the novel mechanisms of action of Taxifolin, which has been widely used as a health supplement with high safety. |
format | Online Article Text |
id | pubmed-9865844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98658442023-01-22 Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis Inoue, Takayuki Fu, Bin Nishio, Miwako Tanaka, Miyako Kato, Hisashi Tanaka, Masashi Itoh, Michiko Yamakage, Hajime Ochi, Kozue Ito, Ayaka Shiraki, Yukihiro Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Inoue, Shian Saeki, Kumiko Enomoto, Atsushi Suganami, Takayoshi Satoh-Asahara, Noriko Nutrients Article The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcinoma. Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid with antioxidant and anti-inflammatory properties commonly found in various foods and health supplement products. In this study, we demonstrated that Taxifolin treatment markedly prevented the development of hepatic steatosis, chronic inflammation, and liver fibrosis in a murine model of NASH. Its mechanisms include a direct action on hepatocytes to inhibit lipid accumulation. Taxifolin also increased brown adipose tissue activity and suppressed body weight gain through at least two distinct pathways: direct action on brown adipocytes and indirect action via fibroblast growth factor 21 production in the liver. Notably, the Taxifolin treatment after NASH development could effectively prevent the development of liver tumors. Collectively, this study provides evidence that Taxifolin shows pleiotropic effects for the treatment of the NASH continuum. Our data also provide insight into the novel mechanisms of action of Taxifolin, which has been widely used as a health supplement with high safety. MDPI 2023-01-10 /pmc/articles/PMC9865844/ /pubmed/36678220 http://dx.doi.org/10.3390/nu15020350 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Inoue, Takayuki Fu, Bin Nishio, Miwako Tanaka, Miyako Kato, Hisashi Tanaka, Masashi Itoh, Michiko Yamakage, Hajime Ochi, Kozue Ito, Ayaka Shiraki, Yukihiro Saito, Satoshi Ihara, Masafumi Nishimura, Hideo Kawamoto, Atsuhiko Inoue, Shian Saeki, Kumiko Enomoto, Atsushi Suganami, Takayoshi Satoh-Asahara, Noriko Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title | Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title_full | Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title_fullStr | Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title_full_unstemmed | Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title_short | Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis |
title_sort | novel therapeutic potentials of taxifolin for obesity-induced hepatic steatosis, fibrogenesis, and tumorigenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865844/ https://www.ncbi.nlm.nih.gov/pubmed/36678220 http://dx.doi.org/10.3390/nu15020350 |
work_keys_str_mv | AT inouetakayuki noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT fubin noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT nishiomiwako noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT tanakamiyako noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT katohisashi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT tanakamasashi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT itohmichiko noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT yamakagehajime noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT ochikozue noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT itoayaka noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT shirakiyukihiro noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT saitosatoshi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT iharamasafumi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT nishimurahideo noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT kawamotoatsuhiko noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT inoueshian noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT saekikumiko noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT enomotoatsushi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT suganamitakayoshi noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis AT satohasaharanoriko noveltherapeuticpotentialsoftaxifolinforobesityinducedhepaticsteatosisfibrogenesisandtumorigenesis |