Abstract

2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is an active compound extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia, hypercholesterolemia, and diabetes for thousands of years. This study aimed to investigate the protective effects of THSG in an Adriamycin (AD)-induced focal segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in an in vitro system. Mice were treated with THSG (2.5 and 10 mg/kg, oral gavage) for 24 consecutive days. On the third day, mice were intravenously given a single dose of AD (10 mg/kg). At the end of the experiment, plasma and kidney samples were harvested to evaluate the therapeutic effects of THSG. The potential mechanisms of THSG in protecting against AD-induced cytotoxicity were examined using a real-time polymerase chain reaction, immunoblots, lactate dehydrogenase assay, and a cellular oxidized-thiol detection system in a mouse mesangial cell line. In this study, THSG showed concentration-dependent protective effects in ameliorating the progression of AD-induced FSGS. THSG suppressed albuminuria and hypercholesterolemia and reduced the status of lipid peroxidation in urine, plasma, and kidney tissue samples. Furthermore, THSG protected against podocyte damage, reduced renal fibrotic gene expressions, and alleviated the severity of glomerulosclerosis. Treatment of mouse mesangial cells with THSG induced nuclear factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, increased heme oxygenase-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 gene expressions, and reduced cellular thiol oxidation and resistance to AD-induced cytotoxicity. Silencing Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1 (Keap1), abolished these protective effects of THSG. In conclusion, THSG can play a protective role in ameliorating the progression of FSGS in a mouse model through activation of the Nrf2-Keap1 antioxidant pathway. Although a well-designed therapeutic study is needed, THSG may be applied to manage chronic kidney disease.

LanguageEnglish
Pages72-82
Number of pages11
JournalEnvironmental Toxicology
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Glucosides
Doxorubicin
antioxidant
Antioxidants
Focal Segmental Glomerulosclerosis
protein
thiol
gene expression
Cytotoxicity
Proteins
Mesangial Cells
Sulfhydryl Compounds
Gene expression
Hypercholesterolemia
Kidney
plasma
diabetes
Repressor Proteins
Plasmas
Heme Oxygenase-1

Keywords

  • albuminuria
  • chronic kidney disease
  • heme oxygenase 1
  • hypercholesterolemia
  • oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Cite this

@article{c5edcea37b114b9fb0385ade9f4d6e87,
title = "The natural compound 2,3,5,4′-tetrahydroxystilbene-2-O-β-d glucoside protects against adriamycin-induced nephropathy through activating the Nrf2-Keap1 antioxidant pathway",
abstract = "2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is an active compound extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia, hypercholesterolemia, and diabetes for thousands of years. This study aimed to investigate the protective effects of THSG in an Adriamycin (AD)-induced focal segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in an in vitro system. Mice were treated with THSG (2.5 and 10 mg/kg, oral gavage) for 24 consecutive days. On the third day, mice were intravenously given a single dose of AD (10 mg/kg). At the end of the experiment, plasma and kidney samples were harvested to evaluate the therapeutic effects of THSG. The potential mechanisms of THSG in protecting against AD-induced cytotoxicity were examined using a real-time polymerase chain reaction, immunoblots, lactate dehydrogenase assay, and a cellular oxidized-thiol detection system in a mouse mesangial cell line. In this study, THSG showed concentration-dependent protective effects in ameliorating the progression of AD-induced FSGS. THSG suppressed albuminuria and hypercholesterolemia and reduced the status of lipid peroxidation in urine, plasma, and kidney tissue samples. Furthermore, THSG protected against podocyte damage, reduced renal fibrotic gene expressions, and alleviated the severity of glomerulosclerosis. Treatment of mouse mesangial cells with THSG induced nuclear factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, increased heme oxygenase-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 gene expressions, and reduced cellular thiol oxidation and resistance to AD-induced cytotoxicity. Silencing Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1 (Keap1), abolished these protective effects of THSG. In conclusion, THSG can play a protective role in ameliorating the progression of FSGS in a mouse model through activation of the Nrf2-Keap1 antioxidant pathway. Although a well-designed therapeutic study is needed, THSG may be applied to manage chronic kidney disease.",
keywords = "albuminuria, chronic kidney disease, heme oxygenase 1, hypercholesterolemia, oxidative stress",
author = "Lin, {En Yuan} and Uyanga Bayarsengee and Wang, {Ching Chiung} and Chiang, {Yung Hsiao} and Cheng, {Chao Wen}",
year = "2018",
month = "1",
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doi = "10.1002/tox.22496",
language = "English",
volume = "33",
pages = "72--82",
journal = "Environmental Toxicology",
issn = "1520-4081",
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TY - JOUR

T1 - The natural compound 2,3,5,4′-tetrahydroxystilbene-2-O-β-d glucoside protects against adriamycin-induced nephropathy through activating the Nrf2-Keap1 antioxidant pathway

AU - Lin,En Yuan

AU - Bayarsengee,Uyanga

AU - Wang,Ching Chiung

AU - Chiang,Yung Hsiao

AU - Cheng,Chao Wen

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is an active compound extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia, hypercholesterolemia, and diabetes for thousands of years. This study aimed to investigate the protective effects of THSG in an Adriamycin (AD)-induced focal segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in an in vitro system. Mice were treated with THSG (2.5 and 10 mg/kg, oral gavage) for 24 consecutive days. On the third day, mice were intravenously given a single dose of AD (10 mg/kg). At the end of the experiment, plasma and kidney samples were harvested to evaluate the therapeutic effects of THSG. The potential mechanisms of THSG in protecting against AD-induced cytotoxicity were examined using a real-time polymerase chain reaction, immunoblots, lactate dehydrogenase assay, and a cellular oxidized-thiol detection system in a mouse mesangial cell line. In this study, THSG showed concentration-dependent protective effects in ameliorating the progression of AD-induced FSGS. THSG suppressed albuminuria and hypercholesterolemia and reduced the status of lipid peroxidation in urine, plasma, and kidney tissue samples. Furthermore, THSG protected against podocyte damage, reduced renal fibrotic gene expressions, and alleviated the severity of glomerulosclerosis. Treatment of mouse mesangial cells with THSG induced nuclear factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, increased heme oxygenase-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 gene expressions, and reduced cellular thiol oxidation and resistance to AD-induced cytotoxicity. Silencing Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1 (Keap1), abolished these protective effects of THSG. In conclusion, THSG can play a protective role in ameliorating the progression of FSGS in a mouse model through activation of the Nrf2-Keap1 antioxidant pathway. Although a well-designed therapeutic study is needed, THSG may be applied to manage chronic kidney disease.

AB - 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is an active compound extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia, hypercholesterolemia, and diabetes for thousands of years. This study aimed to investigate the protective effects of THSG in an Adriamycin (AD)-induced focal segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in an in vitro system. Mice were treated with THSG (2.5 and 10 mg/kg, oral gavage) for 24 consecutive days. On the third day, mice were intravenously given a single dose of AD (10 mg/kg). At the end of the experiment, plasma and kidney samples were harvested to evaluate the therapeutic effects of THSG. The potential mechanisms of THSG in protecting against AD-induced cytotoxicity were examined using a real-time polymerase chain reaction, immunoblots, lactate dehydrogenase assay, and a cellular oxidized-thiol detection system in a mouse mesangial cell line. In this study, THSG showed concentration-dependent protective effects in ameliorating the progression of AD-induced FSGS. THSG suppressed albuminuria and hypercholesterolemia and reduced the status of lipid peroxidation in urine, plasma, and kidney tissue samples. Furthermore, THSG protected against podocyte damage, reduced renal fibrotic gene expressions, and alleviated the severity of glomerulosclerosis. Treatment of mouse mesangial cells with THSG induced nuclear factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, increased heme oxygenase-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 gene expressions, and reduced cellular thiol oxidation and resistance to AD-induced cytotoxicity. Silencing Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1 (Keap1), abolished these protective effects of THSG. In conclusion, THSG can play a protective role in ameliorating the progression of FSGS in a mouse model through activation of the Nrf2-Keap1 antioxidant pathway. Although a well-designed therapeutic study is needed, THSG may be applied to manage chronic kidney disease.

KW - albuminuria

KW - chronic kidney disease

KW - heme oxygenase 1

KW - hypercholesterolemia

KW - oxidative stress

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DO - 10.1002/tox.22496

M3 - Article

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JO - Environmental Toxicology

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SN - 1520-4081

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