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钩藤通过调节氧化应激而非生物碱活性对 Walker-256 肿瘤发挥广泛的抗肿瘤作用。

Uncaria tomentosa exerts extensive anti-neoplastic effects against the Walker-256 tumour by modulating oxidative stress and not by alkaloid activity.

机构信息

Pharmacology Department, Federal University of Paraná, Brazil.

出版信息

PLoS One. 2013;8(2):e54618. doi: 10.1371/journal.pone.0054618. Epub 2013 Feb 7.

Abstract

This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg(-1)) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

摘要

本研究旨在比较钩藤(UT)粗水醇提取物与从其分离得到的两种馏分的抗肿瘤作用。这两种馏分分别为氯仿(CHCl3)和正丁醇(BuOH),分别富含五环吲哚生物碱(POA)和抗氧化物质。癌症模型是雄性 Wistar 大鼠下肢皮下接种 Walker-256 肿瘤细胞。接种后,通过灌胃给予 BHE 提取物(50mg/kg(-1))或其馏分(按馏分过程的产量)或载体(对照),持续 14 天。还包括未接种肿瘤或用 UT 治疗的个体的基线值。治疗后,分析肿瘤体积和质量、血浆生化、肝和肿瘤的氧化应激、肝和肿瘤匀浆中 TNF-α 水平以及存活率。BHE 提取物及其 BuOH 馏分均成功降低了肿瘤重量和体积,并调节了抗氧化系统。肝 TNF-α 水平表明 BHE 提取物比其 BuOH 馏分的作用更大。重要的是,BHE 提取物及其 BuOH 馏分均增加了荷瘤动物的存活时间。相反,CHCl3 馏分无效。这些数据代表了 UT 抗肿瘤活性中氧化应激调节重要性的体内证明,并且证明了在该肿瘤系的原发性肿瘤中分离的 POA 缺乏活性。这些作用可能是由于具有抗氧化特性的物质的协同组合所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a77c/3567083/e5265fc60052/pone.0054618.g001.jpg

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