Lee Dahae, Lee Seoung Rak, Park Bang Ju, Song Ji Hoon, Kim Jung Kyu, Ko Yuri, Kang Ki Sung, Kim Ki Hyun
College of Korean Medicine, Gachon University, Seongnam 13120, Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Plants (Basel). 2021 Nov 17;10(11):2481. doi: 10.3390/plants10112481.
The aim of this study was to explore the protective effects of bioactive compounds from the fruit of the mulberry tree ( L.) against cisplatin-induced apoptosis in LLC-PK1 pig kidney epithelial cells. fruit is a well-known edible fruit commonly used in traditional folk medicine. Chemical investigation of fruit resulted in the isolation and identification of six phytosterols (-). Their structures were determined as 7-ketositosterol (), stigmast-4-en-3β-ol-6-one (), (3β,6α)-stigmast-4-ene-3,6-diol (), stigmast-4-ene-3β,6β-diol (), 7β-hydroxysitosterol 3-O-β-d-glucoside (), and 7α-hydroxysitosterol 3-O-β-d-glucoside () 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 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 decreased the upregulated phosphorylation of p38 and c-Jun N-terminal kinase (JNK) following cisplatin treatment. In addition, compound 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 in LLC-PK1 cells, thereby supporting the potential of 7-ketositosterol () as an adjuvant candidate for treating cisplatin-induced nephrotoxicity.
本研究旨在探讨桑树果实中的生物活性化合物对顺铂诱导的LLC-PK1猪肾上皮细胞凋亡的保护作用。桑椹是一种著名的可食用果实，常用于传统民间医学。对桑椹果实进行化学研究，分离并鉴定出6种植物甾醇（-）。通过分析它们的物理和光谱数据以及液相色谱/质谱数据，确定其结构分别为7-酮基谷甾醇（）、豆甾-4-烯-3β-醇-6-酮（）、（3β,6α）-豆甾-4-烯-3,6-二醇（）、豆甾-4-烯-3β,6β-二醇（）、7β-羟基谷甾醇3-O-β-D-葡萄糖苷（）和7α-羟基谷甾醇3-O-β-D-葡萄糖苷（）。所有化合物均对顺铂诱导的LLC-PK1细胞损伤具有保护作用，使顺铂诱导的细胞毒性提高至对照值的80%以上。化合物在相对较低浓度下表现出最佳效果，可抑制顺铂处理后凋亡细胞的百分比。通过蛋白质免疫印迹分析确定其分子机制。用化合物处理LLC-PK1细胞可降低顺铂处理后p38和c-Jun氨基末端激酶（JNK）上调的磷酸化水平。此外，化合物在顺铂诱导的LLC-PK1细胞中显著抑制裂解的半胱天冬酶-3。综上所述，这些发现表明化合物在LLC-PK1细胞中显著抑制了顺铂诱导的凋亡，从而支持了7-酮基谷甾醇（）作为治疗顺铂诱导的肾毒性辅助候选药物的潜力。
