Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
- Protective Effect of Artemisia argyi and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells
- 이재욱; Dahae Lee; Cahng-Eop Kim; Sa-Yoon Park; Kem Ok Kim; NguyenTuan Hiep; Dongho Lee; Hyuk-Jai Jang; Ki Sung Kang
- nephrotoxicity; iodixanol; MAPK; caspase; artemisia argyi; flavonoid
- Issue Date
- International journal of molecular sciences
- VOL 19, NO 5-1387-18
- 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-
) 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- and inhibition of MAPK phosphorylation and activation of caspases.
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