Identification of Renoprotective Phytosterols from Mulberry (Morus alba) Fruit against Cisplatin-Induced Cytotoxicity in LLC-PK1 Kidney Cells
- Authors
- Lee, Dahae; Lee, Seoung Rak; Park, Bang Ju; Song, Ji Hoon; Kim, Jung Kyu; Ko, Yuri; Kang, Ki Sung; Kim, Ki Hyun
- Issue Date
- Nov-2021
- Publisher
- MDPI
- Keywords
- LLC-PK1; MAPKs; Morus alba; Mulberry; Nephrotoxicity; Phytosterols
- Citation
- Plants, v.10, no.11
- Journal Title
- Plants
- Volume
- 10
- Number
- 11
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/82945
- DOI
- 10.3390/plants10112481
- ISSN
- 2223-7747
- Abstract
- 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 commonly used in traditional folk medicine. Chemical investigation of M. alba fruit resulted in the isolation and identification of six phytosterols (1–6). Their structures were determined as 7-ketositosterol (1), stigmast-4-en-3β-ol-6-one (2), (3β,6α)-stigmast-4-ene-3,6-diol (3), stigmast-4-ene-3β,6β-diol (4), 7β-hydroxysitosterol 3-O-β-D-glucoside (5), and 7α-hydroxysitosterol 3-O-β-D-glucoside (6) 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 1 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 1 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 1 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 1 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol (1) as an adjuvant candidate for treating cisplatin-induced nephrotoxicity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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