Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice

Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously,...

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Main Authors: Lin Dong, Lei Yin, Hongfeng Quan, Yuankui Chu, Jincai Lu
Format: Article
Language:English
Published: MDPI AG 2017-10-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/22/10/1755
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author Lin Dong
Lei Yin
Hongfeng Quan
Yuankui Chu
Jincai Lu
author_facet Lin Dong
Lei Yin
Hongfeng Quan
Yuankui Chu
Jincai Lu
author_sort Lin Dong
collection DOAJ
description Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously, we found that the extracts of Elaeagnus mollis leaves had favorable protective effects on acute liver injury. However, the role and mechanisms behind that was elusive. This study examined the hepatoprotective mechanisms of kaempferol-3-O-α-l-arabinopyranosyl-7-O-α-l-rhamnopyra-noside (KAR), a major flavonol glycoside of E. mollis, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. KAR reduces the mouse mortality, protects the normal liver structure, inhibits the serum aspartate aminotransferase (AST) and alamine aminotransferase (ALT) activity and decreases the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and inflammatory cytokines, TNF-α, IL-6, and IL-1β. Furthermore, KAR inhibits the apoptosis of hepatocytes and reduces the expression of TLR4 and NF-κB signaling pathway-related proteins induced by GalN/LPS treatment. These findings suggest that the anti-oxidative, anti-inflammatory, and anti-apoptotic effects of KAR on GalN/LPS-induced acute liver injury were performed through down-regulating the activity of the TLR4 and NF-κB signaling pathways.
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spelling doaj.art-30426ca83afb48db837309908586cb972022-12-22T01:38:21ZengMDPI AGMolecules1420-30492017-10-012210175510.3390/molecules22101755molecules22101755Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in MiceLin Dong0Lei Yin1Hongfeng Quan2Yuankui Chu3Jincai Lu4School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan 750004, ChinaSchool of Pharmacy, Ningxia Medical University, Yinchuan 750004, ChinaDepartment of Laboratory Medicine, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 750004, ChinaSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, ChinaFulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the liver from different factor-induced injury. Previously, we found that the extracts of Elaeagnus mollis leaves had favorable protective effects on acute liver injury. However, the role and mechanisms behind that was elusive. This study examined the hepatoprotective mechanisms of kaempferol-3-O-α-l-arabinopyranosyl-7-O-α-l-rhamnopyra-noside (KAR), a major flavonol glycoside of E. mollis, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. KAR reduces the mouse mortality, protects the normal liver structure, inhibits the serum aspartate aminotransferase (AST) and alamine aminotransferase (ALT) activity and decreases the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and inflammatory cytokines, TNF-α, IL-6, and IL-1β. Furthermore, KAR inhibits the apoptosis of hepatocytes and reduces the expression of TLR4 and NF-κB signaling pathway-related proteins induced by GalN/LPS treatment. These findings suggest that the anti-oxidative, anti-inflammatory, and anti-apoptotic effects of KAR on GalN/LPS-induced acute liver injury were performed through down-regulating the activity of the TLR4 and NF-κB signaling pathways.https://www.mdpi.com/1420-3049/22/10/1755Elaeagnus mollis Dielskaempferol-3-O-α-">l-arabinopyranosyl-7-O-α-">l-rhamnopyranosideacute hepatic failureapoptosisinflammatory responses
spellingShingle Lin Dong
Lei Yin
Hongfeng Quan
Yuankui Chu
Jincai Lu
Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
Molecules
Elaeagnus mollis Diels
kaempferol-3-O-α-
">l-arabinopyranosyl-7-O-α-
">l-rhamnopyranoside
acute hepatic failure
apoptosis
inflammatory responses
title Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
title_full Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
title_fullStr Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
title_full_unstemmed Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
title_short Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice
title_sort hepatoprotective effects of kaempferol 3 o α l arabinopyranosyl 7 o α l rhamnopyranoside on d galactosamine and lipopolysaccharide caused hepatic failure in mice
topic Elaeagnus mollis Diels
kaempferol-3-O-α-
">l-arabinopyranosyl-7-O-α-
">l-rhamnopyranoside
acute hepatic failure
apoptosis
inflammatory responses
url https://www.mdpi.com/1420-3049/22/10/1755
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