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

Abstract

Iodixanol is a non-ionic iso-osmolar contrast agent, but it is a risk factor for kidney damage and increases morbidity and mortality. In this study, we investigated the effect of 9 sesquiterpenes isolated from mugwort (Artemisia argyi) in contrast agent-induced cytotoxicity in LLC-PK1 cells. Cells were exposed to nine sesquiterpene compounds for 2 h, followed by incubation with iodixanol for 3 h. Cell viability was assessed using the Ez-Cytox assay. The level of reactive oxygen species was measured using 2′,7′-dichlorodihydrofluorescein diacetate staining. Apoptotic cell death was detected using annexin V/PI staining. In addition, immunofluorescence staining and western blotting were performed using antibodies against proteins related to apoptosis, oxidative stress, and MAPK pathways. The most effective 3-epi-iso-seco-tanapartholide (compound 8) among the 9 sesquiterpene compounds protected LLC-PK1 cells from iodixanol-induced cytotoxicity, oxidative stress, and apoptotic cell death. Pretreatment with compound 8 reversed iodixanol-induced increases in the expression of JNK, ERK, p38, Bax, caspase-3, and caspase-9. It also reversed the iodixanol-induced decrease in Bcl-2 expression. Furthermore, pretreatment with compound 8 caused nuclear translocation of Nrf2 and upregulated HO-1 via the Nrf2 pathway in iodixanol-treated LLC-PK1 cells. Thus, we demonstrated here that compound 8 isolated from A. argyi has the potential to effectively prevent iodixanol-induced kidney epithelial cell death via the caspase-3/MAPK pathways and HO-1 via the Nrf2 pathway.

Investigation on Fermentation Characteristics and Microbial Communities of Wheat Straw Silage with Different Proportion Artemisia argyi

“…Alpha diversity, commonly measured in terms of Chao1 richness and Shannon diversity, reflects the microbial abundance and species diversity of a single sample [ 54 ]. As shown in Figure 2 , the alpha diversity was higher in AA than in WS before ensiling.…”

Isolation of Secondary Metabolites from Achillea grandifolia Friv. (Asteraceae) and Main Compounds’ Effects on a Glioblastoma Cellular Model

“…Notably, a G2/M cell cycle arrest coupled with an induction of the S phase fraction, especially in the case of U87MG cells, is known to be associated with the anti-glioma activity of natural compounds such as deglucohellebrin [ 18 ], thereby supporting a similar mechanism of action that may be associated with an anti-inflammatory effect and the action of NF-kB transcription factor. Previous studies have revealed that rupicolin A had a protective effect on iodixanol-induced cytotoxicity in LLC-PK1 cells at concentrations of 10 µM, with a cell survival rate of 75.1 ± 1.9% [ 15 ]. The current research offered evidence that natural substances exert anti-cancer effects, thereby suggesting that rupicolin A and B are promising candidates for further research, given the continuous need for novel therapies for the second cause of human mortality [ 57 ].…”

“…Other examples refer to ligustolide-A and arteludovicinolide-A that exhibit anti-inflammatory properties or 1α,6α,8α-trihydroxy-5α,7β H-guaia-3,10,14,11,13-trien-12-oic acid and 1α,6α,8α-trihydroxy-5α,7βH-guaia-3,9,11,13-trien-12-oic acid, which may significantly enhance the proliferation of beneficial macrophages [ 14 ]. Moreover, in a recent study, the protective effect of rupicolin A and acrifolide has been investigated against iodixanol-induced cytotoxicity in cultured renal tubular cells (LLC-PK1), although none of them showed any toxic effect at 25μΜ and 50μΜ, respectively [ 15 ].…”

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/β-Catenin Signaling Pathway

“…Recent studies have shown that it possesses antioxidant, anti-cancer, anti-inflammatory, immunomodulatory, as well as antimicrobial properties Abbreviations: AAEO, Artemisia argyi essential oil; DMEM, Dulbecco's Modified Eagle Medium; EMT, epithelial-mesenchymal transition; HCC, hepatocellular carcinoma; H&E, hematoxylin and eosin staining; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PBS, phosphate buffered saline; RT-qPCR, real-time quantitative PCR. (Li et al, 2018;Lee et al, 2020). A wide range of phytochemicals including essential oils, flavonoids, organic acids, terpenes, polysaccharides, and coumarins have been identified in Artemisia argyi (Song et al, 2019).…”

“…is a famous plant species in traditional Chinese medicine used to control dysmenorrhea, abdominal pain, and inflammation ( Editorial Board of Chinese Pharmacopoeia, 2015 ). Recent studies have shown that it possesses antioxidant, anti-cancer, anti-inflammatory, immunomodulatory, as well as antimicrobial properties ( Li et al, 2018 ; Lee et al, 2020 ). A wide range of phytochemicals including essential oils, flavonoids, organic acids, terpenes, polysaccharides, and coumarins have been identified in Artemisia argyi ( Song et al, 2019 ).…”