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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Main Authors: Dahae Lee, Kyo Bin Kang, Gwi Seo Hwang, You-Kyoung Choi, Tae Kon Kim, Ki Sung Kang
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/11/1614
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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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