Protective Effect of Phenolic Compounds Isolated from Mugwort (Artemisia argyi) against Contrast-Induced Apoptosis in Kidney Epithelium Cell Line LLC-PK1

Abstract

We investigated whether 14 phenolic compounds isolated from Artemisia argyi could prevent the apoptotic damage caused by iodixanol, an iodinated contrast agent, on LLC-PK1 cells. Iodixanol was used to induce cytotoxicity in LLC-PK1 cells. Apoptotic cell death was observed as the fluorescence intensity emitted by annexin V and Hoechst 33342 stains. Western blotting was used to detect specific proteins. Seven phenolic compounds protected against iodixanol-induced LLC-PK1 cell death in a concentration-dependent manner. Among them, methyl caffeate exerted the strongest protective effect, and co-treatment with 50 and 100 μM methyl caffeate decreased intracellular reactive oxygen species elevated by 25 mg/mL iodixanol. In addition, the treatment of LLC-PK1 cells with iodixanol resulted in an increase in apoptotic cell death, which decreased by co-treatment with methyl caffeate. Iodixanol caused a cytotoxicity-related increase in the phosphorylation of extracellular-signal-regulated kinase, c-Jun N-terminal kinase, and P38; and a similar increase in the expression levels of kidney injury molecule-1 and cleaved caspase-3. However, the up-regulation of these proteins was reversed by co-treatment with methyl caffeate. These findings suggest that phenolic compounds isolated from A. argyi play an important role in protecting kidney epithelium cells against apoptotic damage caused by iodixanol.

Neuroprotective Effects of Methyl Caffeate against Hydrogen Peroxide-Induced Cell Damage: Involvement of Caspase 3 and Cathepsin D Inhibition

“…It should be noted that previous studies demonstrated that CA or its derivatives inhibited apoptotic processes in neuronal cells which were induced by various factors (e.g., low potassium level, H 2 O 2 , serum deprivation) [5,8,13,19,40] and our present results extend these data by showing the effects of MC in the oxidative stress-based model. It is also in line with previous data from non-neuronal cells (kidney epithelium cell line LLC-PK) where MC (100 µM) reduced the contrast-induced caspase-3 activity and increased cell survival [54]. However, the MC effects in apoptotic models could be inducer-specific since in our study we not only did not find any protection offered by this compound against neuronal cell damage induced by staurosporine, an activator of caspase-3 dependent apoptosis [55], but we even observed an increased cytotoxicity after concomitant treatment with both agents in UN-SH-SY5Y and in primary neurons.…”

Anti-Apoptotic and Antioxidant Effects of 3-Epi-Iso-Seco-Tanapartholide Isolated from Artemisia argyi against Iodixanol-Induced Kidney Epithelial Cell Death

“…Furthermore, some phenolic compounds, as well as flavonoids isolated from A. argyi , are more effective than NAC against iodixanol-induced damage in LLC-PK1 cells. Among them, artemetin, identified as a flavonoid, and methyl caffeate, identified as a phenolic compound, are responsible for the protective activities against cytotoxicity caused by iodixanol in LLC-PK1 cells [ 15 , 17 ]. Nevertheless, more research is required to understand the biological activities of A. argyi and its phytochemical components in the treatment of nephrotoxicity.…”

Cytotoxic phenolic constituents from the leaves of Ehretia asperula

“…Interestingly, all compounds did not affect the viability of normal cells (monkey kidney VERO cell line) up to 30 μM. Methyl caffeate (2) has been reported as a promising anti-cancer agent by inducing apoptosis (Balachandran et al, 2015;Kim et al, 2019). In this study, compound 1 showed stronger cytotoxic effect than methyl caffeate.…”