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不同独尾草提取物对肝癌(Hep3B)细胞的抗血管生成和细胞毒性潜力:一项体外、卵内和计算机模拟研究。

The anti-angiogenic and cytotoxic potential of different Eremurus spectabilis fractions on hepatocellular carcinoma (Hep3B) cells: An in vitro, in Ovo, and in silico study.

作者信息

Alhalak Nour, Şen Ali, Öter Gamze Nur, Akar Remzi Okan, Ulukaya Engin, Şekerler Turgut

机构信息

Department of Biochemistry, Faculty of Pharmacy, Marmara University, İstanbul, Turkey.

Department of Pharmacognosy, Faculty of Pharmacy, Marmara University, İstanbul, Turkey.

出版信息

Comput Biol Med. 2025 Aug;194:110498. doi: 10.1016/j.compbiomed.2025.110498. Epub 2025 Jun 9.

DOI:10.1016/j.compbiomed.2025.110498
PMID:40494168
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) remains a major health concern, with angiogenesis playing a key role in its progression. Medicinal plants offer valuable anticancer potential. Eremurus spectabilis (ES), traditionally used in folk medicine, has not been fully explored for its anticancer properties. This study investigates its cytotoxicity on Hep3B cells and its anti-angiogenic activity.

METHODS

E. spectabilis fractions (hexane, chloroform, ethyl acetate, and aqueous ethanol) were obtained from the ethanolic extract. The total phenolic content (TPC) was measured, and the active fractions were analyzed using gas chromatography-mass spectrometry (GC-MS). The xCELLigence Real-Time Cell Analyzer was used to evaluate cytotoxicity against Hep3B cells. Anti-angiogenic activity was assessed using the CAM assay, and docking studies were conducted to predict the mechanism of anti-angiogenesis.

RESULTS

ESEA (154.80 ± 0.10 mg/g) had the highest phenolic content, followed by ESC (84.81 ± 6.81 mg/g). Palmitic acid (26%), khusimyl acid (15.9%), glycerol (12.1%), and D-(+)-talofuranose pentakis(trimethylsilyl) ether (9.7%) were the major compounds in ESC, while D-glucopyranose (19.4%), β-D-(+)-talopyranose (15.7%), and D-(-)-tagatofuranose pentakis(trimethylsilyl) ether (13.6%) were among the major compounds in ESEA. All fractions revealed significant cytotoxicity on Hep3B cells, with ESEA (24-h IC: 6.53 μg/mL) and ESAE (24-h IC: 7.89 μg/mL) being more effective. ESC also exhibited strong anti-angiogenic effects by reducing vessel area, length, and branching points. These findings were supported by molecular docking. The major phytochemicals significantly interact with VEGFR-2 and FGFR1.

CONCLUSIONS

E. spectabilis shows a promising dual action for cancer therapy. However, further research is necessary to predict the exact mechanism of action.

摘要

背景

肝细胞癌(HCC)仍然是一个主要的健康问题,血管生成在其进展中起关键作用。药用植物具有宝贵的抗癌潜力。美丽独尾草(ES)传统上用于民间医学,但其抗癌特性尚未得到充分研究。本研究调查了其对Hep3B细胞的细胞毒性及其抗血管生成活性。

方法

从乙醇提取物中获得美丽独尾草的馏分(己烷、氯仿、乙酸乙酯和乙醇水溶液)。测量总酚含量(TPC),并使用气相色谱 - 质谱联用仪(GC - MS)分析活性馏分。使用xCELLigence实时细胞分析仪评估对Hep3B细胞的细胞毒性。使用鸡胚绒毛尿囊膜(CAM)试验评估抗血管生成活性,并进行对接研究以预测抗血管生成机制。

结果

ESEA(154.80±0.10mg/g)的酚含量最高,其次是ESC(84.81±6.81mg/g)。棕榈酸(26%)、阔苞菊酸(15.9%)、甘油(12.1%)和D -(+)-塔罗呋喃糖五(三甲基硅基)醚(9.7%)是ESC中的主要化合物,而D - 吡喃葡萄糖(19.4%)、β - D -(+)-塔罗吡喃糖(15.7%)和D -(-)-塔格呋喃糖五(三甲基硅基)醚(13.6%)是ESEA中的主要化合物。所有馏分对Hep3B细胞均显示出显著的细胞毒性,ESEA(24小时半数抑制浓度:6.53μg/mL)和ESAE(24小时半数抑制浓度:7.89μg/mL)更有效。ESC还通过减少血管面积、长度和分支点表现出强烈的抗血管生成作用。分子对接支持了这些发现。主要植物化学物质与血管内皮生长因子受体 - 2(VEGFR - 2)和成纤维细胞生长因子受体1(FGFR1)有显著相互作用。

结论

美丽独尾草显示出在癌症治疗方面有前景的双重作用。然而,需要进一步研究以预测确切的作用机制。

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