Polydatin protects against acetaminophen-induced hepatotoxicity in mice via anti-oxidative and anti-apoptotic activities

Published on Nov 14, 2018in Food & Function4.171
· DOI :10.1039/C8FO01078A
Yu-Hong Liu19
Estimated H-index: 19
(Guangzhou University of Chinese Medicine),
Qiong-Hui Huang8
Estimated H-index: 8
(Guangzhou University of Chinese Medicine)
+ 7 AuthorsJian-Nan Chen19
Estimated H-index: 19
(Guangzhou University of Chinese Medicine)
Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate D-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.
📖 Papers frequently viewed together
11 Citations
57 Citations
25 Citations
#1Ruibing Feng (UM: University of Macau)H-Index: 8
#2Yang Wang (UM: University of Macau)H-Index: 8
Last. Jian-Bo Wan (UM: University of Macau)H-Index: 39
view all 9 authors...
Abstract Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type...
14 CitationsSource
#1Huan Liang (Xi'an Jiaotong University)H-Index: 1
#2Yang Feng (Shaanxi University of Chinese Medicine)H-Index: 5
Last. Chang Liu (Xi'an Jiaotong University)H-Index: 27
view all 6 authors...
Abstract The present study aimed to investigate the effect of simvastatin on acetaminophen (APAP) hepatotoxicity in a mouse model. Male C57BL/6 mice were allocated into the following groups: control, APAP, APAP+SIM10, APAP+SIM20, APAP+SIM100 and APAP+SIM200 groups. The mice in the APAP group were treated with saline intraperitoneally (i.p.) 72 h before and 24 h or 72 h after APAP challenge (i.p., 400 mg/kg of APAP). The simvastatin-treated groups were treated with different doses of simvastatin ...
11 CitationsSource
#1Hanan A. El-Bakry (Minia University)H-Index: 7
#2G. El-Sherif (Minia University)H-Index: 1
Last. Rehab M. Rostom (Minia University)H-Index: 1
view all 3 authors...
Abstract Green tea extract (GTE) is considered to be endowed with countless healthful properties. Nevertheless, data concerning the hepatoprotective activities of GTE and its utilization as a therapeutic intervention for paracetamol (APAP) overdose are conflicting and intriguing. The present study was undertaken to address the effect of therapeutic dose of GTE on the liver, evaluate the potential hepatoprotection of GTE against APAP-induced hepatotoxicity, asses the regenerative capacity of the ...
11 CitationsSource
#1Zi WangH-Index: 15
#2Jun-nan HuH-Index: 10
Last. Wei LiH-Index: 10
view all 6 authors...
Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG plays such a liver protection effect. The objective of the current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatoto...
42 CitationsSource
#1Xinyi Zhao (Lanzhou University)H-Index: 2
#2Rui Li (Guangdong Pharmaceutical University)H-Index: 1
Last. Yiqing Wang (Lanzhou University)H-Index: 11
view all 10 authors...
Abstract Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol, has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl4) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not...
25 CitationsSource
#1Ugo IndraccoloH-Index: 10
#2S. R. IndraccoloH-Index: 7
Last. Fiorenzo Mignini (University of Camerino)H-Index: 19
view all 3 authors...
Objectives. 1. To demonstrate clinical effectiveness of micronized palmitoylethanolamide-trans-polydatin combination in reducing endometriotic chronic pelvic pain (main objective); 2. To reduce other endometriotic-associated pain; 3. To assess the effects of this treatment in patient sub-groups; 4. To demonstrate that such therapy modifies natural history of the disease. Data sources. Systematic reviews of PubMed, SCIELO, Scopus, and AJOL, without regard to time frame and other limits. Study eli...
13 CitationsSource
#1Zainul Amiruddin Zakaria (UPM: Universiti Putra Malaysia)H-Index: 43
#2Farah Hidayah Kamisan (UPM: Universiti Putra Malaysia)H-Index: 6
Last. Muhammad Nazrul Hakim Abdullah (UPM: Universiti Putra Malaysia)H-Index: 7
view all 7 authors...
Abstract Background The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. Methods A group of mice ( n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats ( n = 6) were used and each received as follows: Group 1 (normal control; pretreated wit...
15 CitationsSource
#1Seung Kim (Chosun University)H-Index: 9
#2Kyu Min Kim (SNU: Seoul National University)H-Index: 4
Last. Sung Hwan Ki (Chosun University)H-Index: 24
view all 10 authors...
Abstract Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that Sestrin2 (Sesn2) protects against d -galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein ...
26 CitationsSource
#1Taofeek O. AjiboyeH-Index: 18
#2Fatimah M. AhmadH-Index: 1
Last. Taofik O. SunmonuH-Index: 17
view all 7 authors...
AbstractContext: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are widely used in the management of liver disorders in Nigeria. However, no there is no scientific validation to support this use.Objective: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was investigated in acetaminophen-induced liver injury mice.Materials and methods: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in acetaminophen-induced hepatic...
13 CitationsSource
#1Meghana Koneru (Indian Institute of Chemical Technology)H-Index: 6
#2Bidya Dhar Sahu (Indian Institute of Chemical Technology)H-Index: 16
Last. Ramakrishna Sistla (Indian Institute of Chemical Technology)H-Index: 32
view all 8 authors...
Abstract Background Alcohol, a most commonly consumed beverage, is the foremost cause of liver injury throughout the world. Polydatin, a stilbenoid glucoside, was known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders. Purpose The present study was intended at investigating the hepatoprotective efficacy of polydatin against acute-alcohol induced liver injury model in mice. Study design C57BL/6 mice were fed with five doses of 50% ethy...
25 CitationsSource
Cited By11
#1Linlin Qu (Northwest University (China))H-Index: 5
#2Rongzhan Fu (Northwest University (China))H-Index: 9
Last. Daidi Fan (Northwest University (China))H-Index: 25
view all 4 authors...
Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently used in clinical practice for APAP, there is a need to develop new therapies that can provide extensive protection against AIALI. Ginsenoside Rk3 is a rare ginsenoside extracted from Panax notoginseng and a previous study has reported its excellent hepatoprotective function. In this study, we expl...
#1Laura Risaliti (UniFI: University of Florence)H-Index: 5
#2Xuan Yu (Tianjin University of Traditional Chinese Medicine)H-Index: 1
Last. Anna Rita Bilia (UniFI: University of Florence)H-Index: 52
view all 6 authors...
Abstract Aim of this work was to prepare and characterize a hydroxyethyl cellulose hydrogel loaded with ascosomes, nanovesicles based on phosphatidylcholine plus ascorbyl octanoate (ASC8) or ascorbyl decanoate (ASC1), and khellin (2 mg/mL), for topical use. ASC10 vesicles were selected for the hydrogel formulation because of the best biopharmaceutical characteristics, namely size of 115 nm, PDI of 0.26, ζ-potential of −40.1 meV, EE% of 90.2%. After 24 h the in vitro release of khellin was more t...
2 CitationsSource
#1Yongpeng Wang (Kunming University of Science and Technology)H-Index: 1
#2Lei Tian (Kunming University of Science and Technology)H-Index: 1
Last. Gui-Guang Cheng (Kunming University of Science and Technology)H-Index: 15
view all 8 authors...
The tender leaves and buds of Vaccinium dunalianum Wight have been traditionally processed as folk tea, known as Que Zui tea (QT), with a wide range of benefits to humans. In this study, Que Zui tea hot-water extract (QTW) and aqueous-ethanol extract (QTE) were tested for their effectiveness to alleviate acetaminophen (APAP)-induced liver damage. QTW and QTE significantly inhibited the alanine aminotransaminase, aspartate aminotransaminase, tumor necrosis factor-α, interleukin-6, and interleukin...
2 CitationsSource
#1Meiying SuH-Index: 1
#2Chao DongH-Index: 1
Last. Maojin ZhouH-Index: 1
view all 5 authors...
In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MSn) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans-resveratrol-4'-O-glucuronide (M2'), trans-resveratrol-3-O-glucoside-4'-O-glucuronide (M3), trans-resveratrol-3-O-glucoside-5-O-glucuronide (M3'), trans-resveratrol-3-sulfate (M4) and trans-resveratrol-4'-sulfate ...
#1Yurong Fu (JLU: Jilin University)H-Index: 4
#2Yongcheng Jin (JLU: Jilin University)H-Index: 8
Last. Yue Tian (JLU: Jilin University)
view all 12 authors...
Zearalenone (ZEA) is a mycotoxin of the Fusarium genus that can cause endoplasmic reticulum (ER) stress and Apoptosis in bovine mammary epithelial cells (MAC-T). Polydatin (PD), a glycoside purified from Polygonum cuspidatum, has antioxidant properties. This study aimed to explore whether PD can alleviate ZEA-induced damage on bovine mammary epithelial cells (MAC-T). We found that incasing the concentration of ZEA (0, 7.5, 15, 30, 60, 90, 120, and 240 μM) gradually decreased the cell viability. ...
#1Rosalia CrupiH-Index: 32
#2Marika CordaroH-Index: 26
Last. Salvatore CuzzocreaH-Index: 116
view all 3 authors...
Chronic pain is partially sustained by central sensitization, a synaptic plasticity phenomenon, and enhanced neuronal responsiveness following painful insults in the central pain pathways. Accumulating studies indicates that neuroinflammation in the peripheral and central nervous system also drives central sensitization. The activation of glial cells such as microglia and astrocytes in the spinal cord and brain is a distinctive feature of neuroinflammation, leading to the discharge of pro-inflam...
#1Mengyun Zou (HAU: Huazhong Agricultural University)H-Index: 4
#2Wenlong Yang (HAU: Huazhong Agricultural University)H-Index: 1
Last. Xiuli Peng (HAU: Huazhong Agricultural University)H-Index: 12
view all 7 authors...
Abstract Mycoplasma gallisepticum (MG) infection is the main cause of chronic respiratory disease (CRD) characterized by severe respiratory inflammation in chickens. Polydatin (PD) is a resveratrol glycoside isolated from Polygonum cuspidatum, which has prominent anti-inflammatory effect. The purpose of this study was to investigate the therapeutic effect of PD against MG-induced inflammation in chicken and its underlying mechanism. Histopathological analysis showed that PD treatment (15, 30, an...
4 CitationsSource
#1Xiaofei Fan (Tianjin Medical University General Hospital)H-Index: 5
#2Lin Lin (Tianjin Medical University General Hospital)H-Index: 7
Last. Chao SunH-Index: 5
view all 14 authors...
Abstract Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic,...
9 CitationsSource
#1Cheng Hu (SHU: Shanghai University)H-Index: 3
#2Ying Chen (SHU: Shanghai University)H-Index: 1
Last. Jiaqi Zhang (SHU: Shanghai University)H-Index: 8
view all 5 authors...
We investigated the protective effect of Hyperoside (HPS) on liver injury induced by acetaminophen (APAP) in C57 mice. HPS was administered orally for 7 days and APAP was administered orally on the 7th day. Serum and liver samples were then collected for biochemical analyses, histopathology assessments, and metabolomics studies. Metabolites were assessed using a UHPLC-MS system. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to p...
1 CitationsSource
#1Parvej Ahmad (Integral University)H-Index: 3
#2Sahir Sultan Alvi (Integral University)H-Index: 5
Last. M. Salman Khan (Integral University)H-Index: 18
view all 4 authors...
Abstract Polydatin (PD) is a monocrystalline metabolite from the underground parts of Polygonum cuspidatum Sieb. et Zucc., a member of the Polygonaceae family, which has been traditionally used in Asian countries as both foodstuffs and medicine. PD, also reckoned as pieceid, 3,4′,5-trihydroxystilbene-3-β-D-glucoside, (E)-piceid, (E)-polydatin, and trans-polydatin. It possesses potent biological activities i.e. analgesic, anti-inflammatory, antidiabetic, anticancer, and anti-atherosclerotic prope...
6 CitationsSource