Protective effect of artemisia argyi and its flavonoid constituents against contrast-induced cytotoxicity by iodixanol in LLC-PK1 cells

Dahae Lee, Chang Eop Kim, Sa Yoon Park, Kem Ok Kim, Nguyen Tuan Hiep, Dongho Lee, Hyuk Jai Jang, Jae Wook Lee, Ki Sung Kang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1387
JournalInternational journal of molecular sciences
Volume19
Issue number5
DOIs
Publication statusPublished - 2018 May 7

Keywords

  • Artemisia argyi
  • Caspase
  • Flavonoid
  • Iodixanol
  • MAPK
  • Nephrotoxicity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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