圆参提取物通过抑制肾损伤分子-1、中性粒细胞明胶酶相关脂钙蛋白、NF-κB和半胱天冬酶的表达对顺铂暴露的人胚胎肾-293细胞的保护作用

Q3 Pharmacology, Toxicology and Pharmaceutics

Journal of HerbMed Pharmacology Pub Date : 2022-12-31 DOI:10.34172/jhp.2023.14

Dani Sujana, N. M. Saptarini, S. Sumiwi, J. Levita

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引用次数: 0

摘要

急性肾损伤(AKI)是铂类化疗患者的主要问题。圆参能诱导成骨细胞生成，显著提高胰腺抗氧化酶活性;因此，本研究旨在探讨顺铂对人胚胎肾-293 (HEK-293)细胞的细胞毒性，以及圆圆草乙醇提取物(EEBR)对这种情况的保护作用。方法:采用CCK-8/WST-8试剂评估细胞毒性，通过定量测定1µg/mL顺铂暴露的HEK-293细胞中肾损伤分子-1 (Kim-1)、中性粒细胞明胶酶相关脂钙素(NGAL)、核因子κ b (NF-κB)、凋亡caspase-3、caspase-7基因等肾毒性生物标志物的表达，检测细胞保护活性。结果:顺铂对HEK-293细胞具有高毒性(IC50 = 2.5145 μg/mL)，槲皮素对HEK-293细胞具有中等毒性(IC50 = 185.6225 μg/mL)。EEBR显示IC50 = 40.0655 μg/mL。此外，与未处理的顺铂处理细胞系相比，浓度为5、10和20µg/mL的EEBR对暴露于顺铂的HEK-293细胞具有显著的保护作用(P分别为0.031、0.014和0.046)。定量实时聚合酶链反应(PCR)结果显示，高浓度的EEBR显著抑制了Kim-1基因的表达，低浓度的EEBR显著抑制了NGAL和NF-κB基因的表达。高浓度的EEBR降低了caspase-3的表达。所有浓度的EEBR均刺激caspase-7的表达。结论:本研究观察到的显著的保护活性表明EEBR可能对顺铂的肾细胞有保护作用。

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The protective effect of Boesenbergia rotunda extract on cisplatin-exposed human embryonic kidney-293 cells by inhibiting the expression of kidney injury molecule-1, neutrophil gelatinase associated-lipocalin, NF-κB, and caspases

Introduction: Acute kidney injury (AKI) is a major problem in platinum-based chemotherapy patients. Boesenbergia rotunda can induce the generation of osteoblast cells and significantly increase pancreatic antioxidant enzyme activities; therefore, this study aimed to investigate the cytotoxicity of cisplatin on human embryonic kidney-293 (HEK-293) cells and the protective impact of the ethanol extract of B. rotunda (EEBR) against such conditions. Methods: Cytotoxicity was assessed using the CCK-8/WST-8 reagent, while the protective activity was assayed on 1 µg/mL cisplatin-exposed HEK-293 cells by quantifying the expression of nephrotoxicity biomarkers, e.g., kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated-lipocalin (NGAL), nuclear factor-kappaB (NF-κB), apoptotic caspase-3, and caspase-7 genes, in cisplatin-exposed HEK-293 cells. Results: Cisplatin was confirmed as highly toxic against the HEK-293 cells (IC50 = 2.5145 μg/ mL), whereas quercetin was of moderate toxicity (IC50 = 185.6225 μg/mL). EEBR revealed an IC50 = 40.0655 μg/mL. Moreover, EEBR concentrations of 5, 10, and 20 µg/mL confirmed its remarkable protective activity against cisplatin-exposed HEK-293 cells (P=0.031, 0.014, 0.046, respectively) compared to the cisplatin-treated cell lines without treatment. The quantitative real-time polymerase chain reaction (PCR) revealed that a higher concentration of EEBR significantly suppressed the expression of Kim-1, while lower concentrations of EEBR significantly inhibited NGAL and NF-κB genes. Higher concentrations of EEBR reduced the expression of caspase-3. All concentrations of EEBR stimulated the expression of caspase-7. Conclusion: The significant protective activity observed in this study indicated that EEBR might be beneficial in protecting kidney cells against cisplatin.

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来源期刊

Journal of HerbMed Pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Journal of Herbmed Pharmacology (J Herbmed Pharmacol) is the intersection between medicinal plants and pharmacology. This international journal publishes manuscripts in the fields of medicinal plants, pharmacology and therapeutic. This journal aims to reach all relevant national and international medical institutions and persons in electronic version free of charge. J Herbmed Pharmacol has pursued this aim through publishing editorials, original research articles, reviews, mini-reviews, commentaries, letters to the editor, hypothesis, case reports, epidemiology and prevention, news and views. In this journal, particular emphasis is given to research, both experimental and clinical, aimed at protection/prevention of diseases. A further aim of this journal is to emphasize and strengthen the link between herbalists and pharmacologists. In addition, J Herbmed Pharmacol welcomes basic biomedical as well as pharmaceutical scientific research applied to clinical pharmacology. Contributions in any of these formats are invited for editorial consideration following peer review by at least two experts in the field.