L.乙醇提取物的深入研究：细胞毒性作用、液相色谱-电喷雾电离-四极杆飞行时间串联质谱化学剖析、分子对接及急性毒性研究。

Insights into L. Ethanol Extract: Cytotoxic Effects, LC-ESI-QTOF-MS/MS Chemical Profiling, Molecular Docking, and Acute Toxicity Study.

作者信息

Alruwad Manal I, Salah El Dine Riham, Gendy Abdallah M, Saleh Abdulrahman M, Khalaf Mohamed A, El Hefnawy Hala M, Sabry Manal M

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt.

出版信息

Pharmaceuticals (Basel). 2024 Oct 9;17(10):1347. doi: 10.3390/ph17101347.

DOI:10.3390/ph17101347

PMID:39458988

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11510288/

Abstract

BACKGROUND

In Jordanian traditional medicine, is commonly employed for the management of different diseases. Numerous investigations have documented the cytotoxic properties of different species against numerous types of cancer. Previously, we demonstrated the potential cytotoxicity of against HT-29 colorectal cancer cells. Extending our work, the current research aimed to explore the possible mechanisms underlying its antiproliferative activity with a plant safety evaluation.

METHODS

This study evaluates the extract's impact on the cell cycle, apoptosis, and cell migration through in vitro assays, LC-ESI-QTOF-MS/MS analysis, docking studies, and an acute toxicity evaluation.

RESULTS

The ethanol extract (CEE) induced G2/M phase cell cycle arrest (19.63%), triggered significant apoptosis (41.99%), and inhibited cell migration/wound healing by 28.15%. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed increased expression of the proapoptotic markers BAX (6.03-fold) and caspase-3 (6.59-fold), along with the reduced expression of the antiapoptotic BCL-2, in CEE-treated cells. Moreover, CEE significantly restrained angiogenesis by reducing VEGF mRNA expression by 63.9%. High-resolution LC-ESI-QTOF-MS/MS studies identified 26 metabolites, including phenolic compounds, fatty acids, and triterpenoids. Docking studies suggested that manghaslin had the highest binding affinity for VEGFR-2, followed by calceolarioside B, quercetin 7--rhamnopyranoside, luteolin, and quercetin-3,7--diglucoside. On the other hand, salvadoraside exhibited the highest binding affinity for the inhibition of caspase-3, followed by quercetin-3,7--diglucoside, kaempferol-3,7---L-dirhamnoside, manghaslin, and tectoridin, supporting the observed apoptotic effects. Interestingly, the outcomes further indicate that a single oral administration of up to 5000 mg/kg CEE is safe for consumption.

CONCLUSIONS

These outcomes point to the potential of as a promising candidate for further exploration in cancer therapy.

摘要

背景

在约旦传统医学中，常用于治疗各种疾病。大量研究记录了不同物种对多种类型癌症的细胞毒性特性。此前，我们证明了对HT - 29结肠癌细胞具有潜在的细胞毒性。在拓展我们工作的基础上，当前研究旨在通过植物安全性评估探索其抗增殖活性的潜在机制。

方法

本研究通过体外试验、液相色谱 - 电喷雾电离 - 四极杆飞行时间串联质谱（LC - ESI - QTOF - MS/MS）分析、对接研究和急性毒性评估，评估提取物对细胞周期、凋亡和细胞迁移的影响。

结果

乙醇提取物（CEE）诱导G2/M期细胞周期阻滞（19.63%），引发显著凋亡（41.99%），并抑制细胞迁移/伤口愈合28.15%。定量逆转录聚合酶链反应（qRT - PCR）分析显示，在CEE处理的细胞中，促凋亡标志物BAX（6.03倍）和半胱天冬酶 - 3（6.59倍）的表达增加，同时抗凋亡蛋白BCL - 2的表达降低。此外，CEE通过使VEGF mRNA表达降低63.9%，显著抑制血管生成。高分辨率LC - ESI - QTOF - MS/MS研究鉴定出26种代谢物，包括酚类化合物、脂肪酸和三萜类化合物。对接研究表明，芒果苷对血管内皮生长因子受体 - 2（VEGFR - 2）的结合亲和力最高，其次是洋地黄叶苷B、槲皮素7 - 鼠李糖苷、木犀草素和槲皮素 - 3,7 - 二葡萄糖苷。另一方面，萨尔瓦多苷对抑制半胱天冬酶 - 3的结合亲和力最高，其次是槲皮素 - 3,7 - 二葡萄糖苷、山奈酚 - 3,7 - 二 - L - 鼠李糖苷、芒果苷和鸢尾苷，支持了观察到的凋亡效应。有趣的是，结果进一步表明，单次口服高达5000 mg/kg的CEE是安全的。