Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells

The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (Morus alba L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. Morus alba fruit is a well-known edible fruit commo...

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Autores principales:	Dahae Lee, Seoung Rak Lee, Bang Ju Park, Ji Hoon Song, Jung Kyu Kim, Yuri Ko, Ki Sung Kang, Ki Hyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mulberry <i>Morus alba</i> phytosterols LLC-PK1 nephrotoxicity MAPKs Botany QK1-989
Acceso en línea:	https://doaj.org/article/65844ca2131c42c59a6f874886c4e904
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spelling	oai:doaj.org-article:65844ca2131c42c59a6f874886c4e9042021-11-25T18:46:56ZIdentification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells10.3390/plants101124812223-7747https://doaj.org/article/65844ca2131c42c59a6f874886c4e9042021-11-01T00:00:00Zhttps://www.mdpi.com/2223-7747/10/11/2481https://doaj.org/toc/2223-7747The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (<i>Morus alba</i> L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. <i>Morus alba</i> fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of <i>M. alba</i> fruit resulted in the isolation and identification of six phytosterols (<b>1</b>–<b>6</b>). Their structures were determined as 7-ketositosterol (<b>1</b>), stigmast-4-en-3β-ol-6-one (<b>2</b>), (3β,6α)-stigmast-4-ene-3,6-diol (<b>3</b>), stigmast-4-ene-3β,6β-diol (<b>4</b>), 7β-hydroxysitosterol 3-O-β-<span style="font-variant: small-caps;">d</span>-glucoside (<b>5</b>), and 7α-hydroxysitosterol 3-O-β-<span style="font-variant: small-caps;">d</span>-glucoside (<b>6</b>) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound <b>1</b> displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound <b>1</b> decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound <b>1</b> significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound <b>1</b> in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (<b>1</b>) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.Dahae LeeSeoung Rak LeeBang Ju ParkJi Hoon SongJung Kyu KimYuri KoKi Sung KangKi Hyun KimMDPI AGarticlemulberry<i>Morus alba</i>phytosterolsLLC-PK1nephrotoxicityMAPKsBotanyQK1-989ENPlants, Vol 10, Iss 2481, p 2481 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mulberry <i>Morus alba</i> phytosterols LLC-PK1 nephrotoxicity MAPKs Botany QK1-989
spellingShingle	mulberry <i>Morus alba</i> phytosterols LLC-PK1 nephrotoxicity MAPKs Botany QK1-989 Dahae Lee Seoung Rak Lee Bang Ju Park Ji Hoon Song Jung Kyu Kim Yuri Ko Ki Sung Kang Ki Hyun Kim Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
description	The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree (<i>Morus alba</i> L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. <i>Morus alba</i> fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of <i>M. alba</i> fruit resulted in the isolation and identification of six phytosterols (<b>1</b>–<b>6</b>). Their structures were determined as 7-ketositosterol (<b>1</b>), stigmast-4-en-3β-ol-6-one (<b>2</b>), (3β,6α)-stigmast-4-ene-3,6-diol (<b>3</b>), stigmast-4-ene-3β,6β-diol (<b>4</b>), 7β-hydroxysitosterol 3-O-β-<span style="font-variant: small-caps;">d</span>-glucoside (<b>5</b>), and 7α-hydroxysitosterol 3-O-β-<span style="font-variant: small-caps;">d</span>-glucoside (<b>6</b>) by analyzing their physical and spectroscopic data as well as liquid chromatography/mass spectrometry data. All compounds displayed protective effects against cisplatin-induced LLC-PK1 cell damage, improving cisplatin-induced cytotoxicity to more than 80% of the control value. Compound <b>1</b> displayed the best effect at a relatively low concentration by inhibiting the percentage of apoptotic cells following cisplatin treatment. Its molecular mechanisms were identified using Western blot assays. Treatment of LLC-PK1 cells with compound <b>1</b> decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound <b>1</b> significantly suppressed cleaved caspase-3 in cisplatin-induced LLC-PK1 cells. Taken together, these findings indicated that cisplatin-induced apoptosis was significantly inhibited by compound <b>1</b> in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (<b>1</b>) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.
format	article
author	Dahae Lee Seoung Rak Lee Bang Ju Park Ji Hoon Song Jung Kyu Kim Yuri Ko Ki Sung Kang Ki Hyun Kim
author_facet	Dahae Lee Seoung Rak Lee Bang Ju Park Ji Hoon Song Jung Kyu Kim Yuri Ko Ki Sung Kang Ki Hyun Kim
author_sort	Dahae Lee
title	Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
title_short	Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
title_full	Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
title_fullStr	Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
title_full_unstemmed	Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
title_sort	identification of renoprotective phytosterols from mulberry (<i>morus alba</i>) fruit against cisplatin-induced cytotoxicity in llc-pk1 kidney cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/65844ca2131c42c59a6f874886c4e904
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Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells

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