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.
Highlights
Artemisia is a large genus of herbal plants that are commonly used as functional foods and herbal medicine for the treatment of many diseases, including cancer and inflammation, in Korea, China, and Japan [1,2,3]
The anti-apoptotic effects of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the suppression of mitogen-activated protein kinase (MAPK) and activation of caspases
Flavonoid compounds isolated from the A. argyi extract improved the reduced viability of the cells treated with iodixanol
Summary
Artemisia is a large genus of herbal plants that are commonly used as functional foods and herbal medicine for the treatment of many diseases, including cancer and inflammation, in Korea, China, and Japan [1,2,3] Artemisia extracts and their active compounds show antioxidant and anti-inflammatory activities against stress-related mucosal damage, HCl/EtOH-induced gastric damage, Helicobacter pylori-induced gastric damage, microglial neurotoxicity, and pancreatic and hepatic damage [2,4,5,6,7,8,9,10]. The continued use of contrast media is known to increase the number of cases of contrast-induced acute kidney injury [16], which is the third most common cause of hospital-acquired acute kidney injury [15,17] Many factors such as vascular disease, hypertension, diabetes, and renal function impairment are involved, the mechanisms of contrast-induced nephrotoxicity are not completely understood. The results of this study may aid the identification of the relationship between the structural characteristics of flavonoid compounds and the possible renoprotective effects against contrast-induced nephrotoxicity
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