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Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells

Preventive effects and corresponding molecular mechanisms of mugwort (Artemisia argyi) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found t...

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Autores principales: Lee, Dahae, Kim, Chang-Eop, Park, Sa-Yoon, Kim, Kem Ok, Hiep, Nguyen Tuan, Lee, Dongho, Jang, Hyuk-Jai, Lee, Jae Wook, Kang, Ki Sung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983776/
https://www.ncbi.nlm.nih.gov/pubmed/29735908
http://dx.doi.org/10.3390/ijms19051387
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author Lee, Dahae
Kim, Chang-Eop
Park, Sa-Yoon
Kim, Kem Ok
Hiep, Nguyen Tuan
Lee, Dongho
Jang, Hyuk-Jai
Lee, Jae Wook
Kang, Ki Sung
author_facet Lee, Dahae
Kim, Chang-Eop
Park, Sa-Yoon
Kim, Kem Ok
Hiep, Nguyen Tuan
Lee, Dongho
Jang, Hyuk-Jai
Lee, Jae Wook
Kang, Ki Sung
author_sort Lee, Dahae
collection PubMed
description Preventive effects and corresponding molecular mechanisms of mugwort (Artemisia argyi) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that A. argyi extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases. The flavonoid compounds isolated from A. argyi improved the viability of iodixanol-treated cells against contrast-induced nephrotoxicity. Seven compounds (1, 2, 3, 15, 16, 18, and 19) from 19 flavonoids exerted a significant protective effect. Based on the in silico oral-bioavailability and drug-likeness assessment, which evaluate the drug potential of these compounds, compound 2 (artemetin) showed the highest oral bioavailability (49.55%) and drug-likeness (0.48) values. We further investigated the compound–target–disease network of compound 2, and proliferator-activated receptor gamma (PPAR-γ) emerged as a predicted key marker for the treatment of contrast-induced nephrotoxicity. Consequently, compound 2 was the preferred candidate, and its protective effect was mediated by inhibiting the contrast-induced inflammatory response through activation of PPAR-γ and inhibition of MAPK phosphorylation and activation of caspases.
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spelling pubmed-59837762018-06-05 Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells Lee, Dahae Kim, Chang-Eop Park, Sa-Yoon Kim, Kem Ok Hiep, Nguyen Tuan Lee, Dongho Jang, Hyuk-Jai Lee, Jae Wook Kang, Ki Sung Int J Mol Sci Article Preventive effects and corresponding molecular mechanisms of mugwort (Artemisia argyi) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that A. argyi extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases. The flavonoid compounds isolated from A. argyi improved the viability of iodixanol-treated cells against contrast-induced nephrotoxicity. Seven compounds (1, 2, 3, 15, 16, 18, and 19) from 19 flavonoids exerted a significant protective effect. Based on the in silico oral-bioavailability and drug-likeness assessment, which evaluate the drug potential of these compounds, compound 2 (artemetin) showed the highest oral bioavailability (49.55%) and drug-likeness (0.48) values. We further investigated the compound–target–disease network of compound 2, and proliferator-activated receptor gamma (PPAR-γ) emerged as a predicted key marker for the treatment of contrast-induced nephrotoxicity. Consequently, compound 2 was the preferred candidate, and its protective effect was mediated by inhibiting the contrast-induced inflammatory response through activation of PPAR-γ and inhibition of MAPK phosphorylation and activation of caspases. MDPI 2018-05-07 /pmc/articles/PMC5983776/ /pubmed/29735908 http://dx.doi.org/10.3390/ijms19051387 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Dahae
Kim, Chang-Eop
Park, Sa-Yoon
Kim, Kem Ok
Hiep, Nguyen Tuan
Lee, Dongho
Jang, Hyuk-Jai
Lee, Jae Wook
Kang, Ki Sung
Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title_full Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title_fullStr Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title_full_unstemmed Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title_short Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
title_sort protective effect of artemisia argyi and its flavonoid constituents against contrast-induced cytotoxicity by iodixanol in llc-pk1 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983776/
https://www.ncbi.nlm.nih.gov/pubmed/29735908
http://dx.doi.org/10.3390/ijms19051387
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