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Open AccessArticle

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

1
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
2
College of Korean Medicine, Gachon University, Seongnam 13120, Korea
3
Department of Biosystems and Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Korea
4
Department of Surgery, University of Ulsan College of Medicine, Seoul 05505, Korea
5
Natural Constituent Research Center, Korea Institute of Science and Technology, Gangnung 210-340, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(5), 1387; https://doi.org/10.3390/ijms19051387
Received: 13 April 2018 / Revised: 4 May 2018 / Accepted: 4 May 2018 / Published: 7 May 2018
(This article belongs to the Special Issue Traditional Medicine – Unraveling Its Molecular Mechanism)
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. View Full-Text
Keywords: nephrotoxicity; iodixanol; MAPK; caspase; Artemisia argyi; flavonoid nephrotoxicity; iodixanol; MAPK; caspase; Artemisia argyi; flavonoid
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MDPI and ACS Style

Lee, D.; Kim, C.-E.; Park, S.-Y.; Kim, K.O.; Hiep, N.T.; Lee, D.; Jang, H.-J.; Lee, J.W.; Kang, K.S. Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells. Int. J. Mol. Sci. 2018, 19, 1387. https://doi.org/10.3390/ijms19051387

AMA Style

Lee D, Kim C-E, Park S-Y, Kim KO, Hiep NT, Lee D, Jang H-J, Lee JW, Kang KS. Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells. International Journal of Molecular Sciences. 2018; 19(5):1387. https://doi.org/10.3390/ijms19051387

Chicago/Turabian Style

Lee, Dahae; Kim, Chang-Eop; Park, Sa-Yoon; Kim, Kem O.; Hiep, Nguyen T.; Lee, Dongho; Jang, Hyuk-Jai; Lee, Jae W.; Kang, Ki S. 2018. "Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells" Int. J. Mol. Sci. 19, no. 5: 1387. https://doi.org/10.3390/ijms19051387

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