Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway

As a natural active substance, dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the therapeutic effect of DHM on liver fibrosis, which has become a liver disease threatening the health of people around the world, has not been studied to date. The purpose of thi...

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Autores principales:	Yingchun Zhao, Xinglong Liu, Chuanbo Ding, Yan Gu, Wencong Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dihydromyricetin liver fibrosis NF-κB signaling pathway inflammation hepatic stellate cell activation anti-apoptosis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2a2a7462f8fa45a19b213c49e478ef9b
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spelling	oai:doaj.org-article:2a2a7462f8fa45a19b213c49e478ef9b2021-11-15T06:12:04ZDihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway1663-981210.3389/fphar.2021.783886https://doaj.org/article/2a2a7462f8fa45a19b213c49e478ef9b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.783886/fullhttps://doaj.org/toc/1663-9812As a natural active substance, dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the therapeutic effect of DHM on liver fibrosis, which has become a liver disease threatening the health of people around the world, has not been studied to date. The purpose of this study was to investigate the effect of DHM as a new nutritional supplement on thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was established by intraperitoneal injection of TAA (200 mg/kg, every 3 days) for 8 weeks, and oral administration of DHM (20 mg/kg and 40 mg/kg, daily) after 4 weeks of TAA-induced liver fibrosis. The results showed that DHM treatment significantly inhibited the activities of alanine aminotransferase (ALT) (37.81 ± 7.62 U/L) and aspartate aminotransferase (AST) (55.18 ± 10.94 U/L) in serum of liver fibrosis mice, and increased the levels of superoxide dismutase (SOD) and glutathione (GSH) while reversed the level of malondialdehyde (MDA). In addition, histopathological examination illustrated that TAA induced the inflammatory infiltration, apoptosis and fibroatherosclerotic deposition in liver, which was further confirmed by western-blot and immunofluorescence staining. Moreover, DHM inhibited hepatocyte apoptosis by regulating the phosphorylation level of phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT) and its downstream apoptotic protein family. Interestingly, immunofluorescence staining showed that DHM treatment significantly inhibited alpha smooth muscle actin (α-SMA), which was a marker of hepatic stellate cell activation, and regulated the expression of transforming growth factor (TGF-β1). Importantly, supplementation with DHM significantly inhibited the release of nuclear factor kappa-B (NF-κB) signaling pathway and pro-inflammatory factors in liver tissue induced by TAA, and improved liver fiber diseases, such as tumor necrosis factor alpha (TNF-α) and recombinant rat IL-1β (IL-1β). In conclusion, the evidence of this study revealed that DHM is a potential hepatoprotective and health factor, and which also provides the possibility for the treatment of liver fibrosis.Yingchun ZhaoXinglong LiuChuanbo DingYan GuWencong LiuWencong LiuFrontiers Media S.A.articledihydromyricetinliver fibrosisNF-κB signaling pathwayinflammationhepatic stellate cell activationanti-apoptosisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dihydromyricetin liver fibrosis NF-κB signaling pathway inflammation hepatic stellate cell activation anti-apoptosis Therapeutics. Pharmacology RM1-950
spellingShingle	dihydromyricetin liver fibrosis NF-κB signaling pathway inflammation hepatic stellate cell activation anti-apoptosis Therapeutics. Pharmacology RM1-950 Yingchun Zhao Xinglong Liu Chuanbo Ding Yan Gu Wencong Liu Wencong Liu Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
description	As a natural active substance, dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the therapeutic effect of DHM on liver fibrosis, which has become a liver disease threatening the health of people around the world, has not been studied to date. The purpose of this study was to investigate the effect of DHM as a new nutritional supplement on thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was established by intraperitoneal injection of TAA (200 mg/kg, every 3 days) for 8 weeks, and oral administration of DHM (20 mg/kg and 40 mg/kg, daily) after 4 weeks of TAA-induced liver fibrosis. The results showed that DHM treatment significantly inhibited the activities of alanine aminotransferase (ALT) (37.81 ± 7.62 U/L) and aspartate aminotransferase (AST) (55.18 ± 10.94 U/L) in serum of liver fibrosis mice, and increased the levels of superoxide dismutase (SOD) and glutathione (GSH) while reversed the level of malondialdehyde (MDA). In addition, histopathological examination illustrated that TAA induced the inflammatory infiltration, apoptosis and fibroatherosclerotic deposition in liver, which was further confirmed by western-blot and immunofluorescence staining. Moreover, DHM inhibited hepatocyte apoptosis by regulating the phosphorylation level of phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT) and its downstream apoptotic protein family. Interestingly, immunofluorescence staining showed that DHM treatment significantly inhibited alpha smooth muscle actin (α-SMA), which was a marker of hepatic stellate cell activation, and regulated the expression of transforming growth factor (TGF-β1). Importantly, supplementation with DHM significantly inhibited the release of nuclear factor kappa-B (NF-κB) signaling pathway and pro-inflammatory factors in liver tissue induced by TAA, and improved liver fiber diseases, such as tumor necrosis factor alpha (TNF-α) and recombinant rat IL-1β (IL-1β). In conclusion, the evidence of this study revealed that DHM is a potential hepatoprotective and health factor, and which also provides the possibility for the treatment of liver fibrosis.
format	article
author	Yingchun Zhao Xinglong Liu Chuanbo Ding Yan Gu Wencong Liu Wencong Liu
author_facet	Yingchun Zhao Xinglong Liu Chuanbo Ding Yan Gu Wencong Liu Wencong Liu
author_sort	Yingchun Zhao
title	Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
title_short	Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
title_full	Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
title_fullStr	Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
title_full_unstemmed	Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway
title_sort	dihydromyricetin reverses thioacetamide-induced liver fibrosis through inhibiting nf-κb-mediated inflammation and tgf-β1-regulated of pi3k/akt signaling pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2a2a7462f8fa45a19b213c49e478ef9b
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Dihydromyricetin Reverses Thioacetamide-Induced Liver Fibrosis Through Inhibiting NF-κB-Mediated Inflammation and TGF-β1-Regulated of PI3K/Akt Signaling Pathway

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