Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death
Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Zizip...
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2021-10-01
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author | Dahae Lee Kyo Bin Kang Gwi Seo Hwang You-Kyoung Choi Tae Kon Kim Ki Sung Kang |
author_facet | Dahae Lee Kyo Bin Kang Gwi Seo Hwang You-Kyoung Choi Tae Kon Kim Ki Sung Kang |
author_sort | Dahae Lee |
collection | DOAJ |
description | Cisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Ziziphus jujuba</i> Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from <i>Z. jujuba</i> against cisplatin-induced kidney epithelial cell death. |
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spelling | doaj.art-b93a0c0258d649e8a14cc10417976a042023-11-22T22:33:46ZengMDPI AGBiomolecules2218-273X2021-10-011111161410.3390/biom11111614Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell DeathDahae Lee0Kyo Bin Kang1Gwi Seo Hwang2You-Kyoung Choi3Tae Kon Kim4Ki Sung Kang5College of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Pharmacy, Sookmyung Women’s University, Seoul 04310, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Science & Engineering, Jungwon University, Chungbuk 28024, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaCisplatin is a platinum-based chemotherapeutic agent for treating solid tumors; however, it presents a risk factor for nephropathy. In the present study, we investigated the antioxidant and anti-inflammatory effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from <i>Ziziphus jujuba</i> Mill. in LLC-PK1 cells following cisplatin-induced cytotoxicity. These cells were exposed to 3DC2ME for 2 h, followed by treatment with cisplatin for 24 h. The treated cells were subjected to cell viability analysis using the Ez-Cytox assay. Reactive oxygen species (ROS) were detected via 2′, 7′- dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In addition, western blotting and fluorescent immunostaining were performed to evaluate protein expressions related to oxidative stress and inflammation pathways. Pretreatment with 3DC2ME protected LLC-PK1 cells from cisplatin-induced cytotoxicity and oxidative stress. In addition, pretreatment with 3DC2ME upregulated heme oxygenase 1 (HO-1) via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the cisplatin-treated LLC-PK1 cells. Furthermore, the increase in the expressions of IκB kinase α/β (IKKα/β), inhibitor of kappa B alpha (IκBα), nuclear factor kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in these cells was inhibited. These results provide basic scientific evidence for understanding the antioxidant and anti-inflammatory effects of 3DC2ME isolated from <i>Z. jujuba</i> against cisplatin-induced kidney epithelial cell death.https://www.mdpi.com/2218-273X/11/11/1614<i>Ziziphus jujuba</i> Mill.LLC-PK1nephrotoxicityoxidative stressinflammation |
spellingShingle | Dahae Lee Kyo Bin Kang Gwi Seo Hwang You-Kyoung Choi Tae Kon Kim Ki Sung Kang Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death Biomolecules <i>Ziziphus jujuba</i> Mill. LLC-PK1 nephrotoxicity oxidative stress inflammation |
title | Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death |
title_full | Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death |
title_fullStr | Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death |
title_full_unstemmed | Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death |
title_short | Antioxidant and Anti-Inflammatory Effects of 3-Dehydroxyceanothetric Acid 2-Methyl Ester Isolated from <i>Ziziphus jujuba</i> Mill. against Cisplatin-Induced Kidney Epithelial Cell Death |
title_sort | antioxidant and anti inflammatory effects of 3 dehydroxyceanothetric acid 2 methyl ester isolated from i ziziphus jujuba i mill against cisplatin induced kidney epithelial cell death |
topic | <i>Ziziphus jujuba</i> Mill. LLC-PK1 nephrotoxicity oxidative stress inflammation |
url | https://www.mdpi.com/2218-273X/11/11/1614 |
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