Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress
Cholestatic liver injury is a chronic disease caused by the retention of toxic hydrophobic bile salts in the liver, but lack of efficient therapy. Here, we identified that polydatin (PD), a natural precursor of resveratrol (RES), has potent detoxification effects on cholestatic liver injury. PD inhi...
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Elsevier
2019-04-01
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Series: | Journal of Functional Foods |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S175646461930091X |
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author | Jinan Fang Lingling Luo Zunli Ke Chuhe Liu Liufang Yin Yin Yao Qin Feng Cheng Huang Peiyong Zheng Shengjie Fan |
author_facet | Jinan Fang Lingling Luo Zunli Ke Chuhe Liu Liufang Yin Yin Yao Qin Feng Cheng Huang Peiyong Zheng Shengjie Fan |
author_sort | Jinan Fang |
collection | DOAJ |
description | Cholestatic liver injury is a chronic disease caused by the retention of toxic hydrophobic bile salts in the liver, but lack of efficient therapy. Here, we identified that polydatin (PD), a natural precursor of resveratrol (RES), has potent detoxification effects on cholestatic liver injury. PD inhibited hepatocellular apoptosis and attenuated serum alanine aminotransferase (ALT), aspartate transaminase (AST), total bile acid (TBA), alkaline phosphatase (ALP) and total bilirubin (TBIL) levels in the cholestatic mice induced by alpha-naphthylisothiocyanate (ANIT) and bile duct ligation (BDL). Mechanistically, PD reduced malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) activity, suppressed endoplasmic reticulum (ER) stress, CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α) and apoptosis in the liver of the mice, suggesting that PD may alleviate cholestatic liver injury via the inhibition of oxidative stress, ER stress and apoptosis. Our data indicate that PD may be a phytoalexin for cholestatic liver diseases. |
first_indexed | 2024-12-16T17:09:07Z |
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id | doaj.art-3c20ec25892849b99a5e1160a6a1b8e2 |
institution | Directory Open Access Journal |
issn | 1756-4646 |
language | English |
last_indexed | 2024-12-16T17:09:07Z |
publishDate | 2019-04-01 |
publisher | Elsevier |
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series | Journal of Functional Foods |
spelling | doaj.art-3c20ec25892849b99a5e1160a6a1b8e22022-12-21T22:23:27ZengElsevierJournal of Functional Foods1756-46462019-04-0155175183Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stressJinan Fang0Lingling Luo1Zunli Ke2Chuhe Liu3Liufang Yin4Yin Yao5Qin Feng6Cheng Huang7Peiyong Zheng8Shengjie Fan9Drug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaInstitute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaDrug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Drug Discovery Laboratory, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Cholestatic liver injury is a chronic disease caused by the retention of toxic hydrophobic bile salts in the liver, but lack of efficient therapy. Here, we identified that polydatin (PD), a natural precursor of resveratrol (RES), has potent detoxification effects on cholestatic liver injury. PD inhibited hepatocellular apoptosis and attenuated serum alanine aminotransferase (ALT), aspartate transaminase (AST), total bile acid (TBA), alkaline phosphatase (ALP) and total bilirubin (TBIL) levels in the cholestatic mice induced by alpha-naphthylisothiocyanate (ANIT) and bile duct ligation (BDL). Mechanistically, PD reduced malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) activity, suppressed endoplasmic reticulum (ER) stress, CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α) and apoptosis in the liver of the mice, suggesting that PD may alleviate cholestatic liver injury via the inhibition of oxidative stress, ER stress and apoptosis. Our data indicate that PD may be a phytoalexin for cholestatic liver diseases.http://www.sciencedirect.com/science/article/pii/S175646461930091XPolydatinCholestasisOxidative stressEndoplasmic reticulum stressCHOP |
spellingShingle | Jinan Fang Lingling Luo Zunli Ke Chuhe Liu Liufang Yin Yin Yao Qin Feng Cheng Huang Peiyong Zheng Shengjie Fan Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress Journal of Functional Foods Polydatin Cholestasis Oxidative stress Endoplasmic reticulum stress CHOP |
title | Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
title_full | Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
title_fullStr | Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
title_full_unstemmed | Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
title_short | Polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
title_sort | polydatin protects against acute cholestatic liver injury in mice via the inhibition of oxidative stress and endoplasmic reticulum stress |
topic | Polydatin Cholestasis Oxidative stress Endoplasmic reticulum stress CHOP |
url | http://www.sciencedirect.com/science/article/pii/S175646461930091X |
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