Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice

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Abstract

Ethnopharmacological relevance: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism. Materials and methods: The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice. Results: LJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. Conclusion: We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.

Original languageEnglish
Pages (from-to)391-399
Number of pages9
JournalJournal of Ethnopharmacology
Volume224
DOIs
Publication statusPublished - Oct 5 2018

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Laminaria
Seaweed
Sodium-Hydrogen Antiporter
Chronic Renal Insufficiency
Protein Isoforms
Apoptosis
Kidney
PPAR alpha
Doxorubicin
Fibrosis
fucoxanthin
Nephrectomy
Knockout Mice
Small Interfering RNA
Transfection

Keywords

  • Apoptosis
  • Chronic kidney disease
  • Doxorubicin (Pubchem CID: 443939)
  • Fucoxanthin
  • Fucoxanthin (Pubchem CID: 5281239)
  • Na/H exchanger isoform 1
  • Peroxisome proliferator-activated receptor alpha

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

@article{872b978b628f43958b09b16fc22cafaa,
title = "Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice",
abstract = "Ethnopharmacological relevance: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism. Materials and methods: The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice. Results: LJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. Conclusion: We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.",
keywords = "Apoptosis, Chronic kidney disease, Doxorubicin (Pubchem CID: 443939), Fucoxanthin, Fucoxanthin (Pubchem CID: 5281239), Na/H exchanger isoform 1, Peroxisome proliferator-activated receptor alpha",
author = "Chen, {Yen Cheng} and Cheng, {Chung Yi} and Liu, {Chung Te} and Sue, {Yuh Mou} and Chen, {Tso Hsiao} and Hsu, {Yung Ho} and Hwang, {Pai An} and Chen, {Cheng Hsien}",
year = "2018",
month = "10",
day = "5",
doi = "10.1016/j.jep.2018.06.023",
language = "English",
volume = "224",
pages = "391--399",
journal = "Journal of Ethnopharmacology",
issn = "0378-8741",
publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice

AU - Chen, Yen Cheng

AU - Cheng, Chung Yi

AU - Liu, Chung Te

AU - Sue, Yuh Mou

AU - Chen, Tso Hsiao

AU - Hsu, Yung Ho

AU - Hwang, Pai An

AU - Chen, Cheng Hsien

PY - 2018/10/5

Y1 - 2018/10/5

N2 - Ethnopharmacological relevance: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism. Materials and methods: The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice. Results: LJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. Conclusion: We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.

AB - Ethnopharmacological relevance: Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism. Materials and methods: The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice. Results: LJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. Conclusion: We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.

KW - Apoptosis

KW - Chronic kidney disease

KW - Doxorubicin (Pubchem CID: 443939)

KW - Fucoxanthin

KW - Fucoxanthin (Pubchem CID: 5281239)

KW - Na/H exchanger isoform 1

KW - Peroxisome proliferator-activated receptor alpha

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DO - 10.1016/j.jep.2018.06.023

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