Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) 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 (<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 commo...
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MDPI AG
2021-11-01
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:07:46Z |
| format | Article |
| id | doaj.art-65844ca2131c42c59a6f874886c4e904 |
| institution | Directory Open Access Journal |
| issn | 2223-7747 |
| language | English |
| last_indexed | 2024-03-10T05:07:46Z |
| publishDate | 2021-11-01 |
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| spelling | doaj.art-65844ca2131c42c59a6f874886c4e9042023-11-23T01:06:29ZengMDPI AGPlants2223-77472021-11-011011248110.3390/plants10112481Identification of Renoprotective Phytosterols from Mulberry (<i>Morus alba</i>) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney CellsDahae Lee0Seoung Rak Lee1Bang Ju Park2Ji Hoon Song3Jung Kyu Kim4Yuri Ko5Ki Sung Kang6Ki Hyun Kim7College of Korean Medicine, Gachon University, Seongnam 13120, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaDepartment of Electronic Engineering, Gachon University, Seongnam 13120, KoreaJeju Institute of Korean Medicine, Jeju 63309, KoreaSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, KoreaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USACollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaThe 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.https://www.mdpi.com/2223-7747/10/11/2481mulberry<i>Morus alba</i>phytosterolsLLC-PK1nephrotoxicityMAPKs |
| spellingShingle | 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 Plants mulberry <i>Morus alba</i> phytosterols LLC-PK1 nephrotoxicity MAPKs |
| title | 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_short | 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 |
| topic | mulberry <i>Morus alba</i> phytosterols LLC-PK1 nephrotoxicity MAPKs |
| url | https://www.mdpi.com/2223-7747/10/11/2481 |
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