评价睡茄根提取物对细胞周期和血管生成的影响。

Evaluation of the effect of Withania somnifera root extracts on cell cycle and angiogenesis.

作者信息

Mathur Rajani, Gupta Suresh K, Singh Neeta, Mathur Sandeep, Kochupillai Vinod, Velpandian Thirumurthy

机构信息

Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

出版信息

J Ethnopharmacol. 2006 May 24;105(3):336-41. doi: 10.1016/j.jep.2005.11.020. Epub 2006 Jan 10.

DOI:10.1016/j.jep.2005.11.020

PMID:16412596

Abstract

In the Indian System of Medicine, the medicinal plant, Withania somnifera Dunal (Solanaceae) finds application for numerous ailments including cancer. This study explores the mechanism(s) underlying this property. The hydroalcoholic extract of the roots (WS) was partitioned between chloroform (WS-chloroform) and water (WS-water). Further, WS-chloroform was fractionated (A1-A12) by reverse-phase column chromatography and their withanolide content was quantified by high-performance liquid chromatography (HPLC). Preliminarily, the anti-proliferative activity of all the extracts and fractions was screened against human laryngeal carcinoma (Hep2) cells by microculture tetrazolium assay (MTT). Two extracts (WS and WS-chloroform) and three fractions (A4, A5 and A6) negatively affected Hep2 viability at the concentration of 25 microg/ml and these were further investigated pharmacologically. Flow cytometry revealed cell cycle block and accumulation of hypoploid (sub G1) cells as the mode of anti-proliferative activity of all but A4. Their anti-angiogenic potential was investigated by a chickchorio-allantoic membrane (CAM) wherein a significant inhibition (p<0.0001) of vascular endothelium growth factor (VEGF), induced neovascularization was recorded. The effect was confirmed in vivo by mouse sponge implantation method. These findings suggest that the roots of Withania somnifera possess cell cycle disruption and anti-angiogenic activity, which may be a critical mediator for its anti-cancer action.

摘要

在印度医学体系中，药用植物睡茄（茄科）可用于治疗包括癌症在内的多种疾病。本研究探索了其抗癌特性背后的机制。将睡茄根的水醇提取物（WS）在氯仿（WS - 氯仿）和水（WS - 水）之间进行分配。此外，WS - 氯仿通过反相柱色谱法进行分离（A1 - A12），并通过高效液相色谱法（HPLC）对其睡茄内酯含量进行定量。首先，通过微量培养四氮唑法（MTT）筛选所有提取物和馏分对人喉癌（Hep2）细胞的抗增殖活性。两种提取物（WS和WS - 氯仿）以及三个馏分（A4、A5和A6）在浓度为25微克/毫升时对Hep2细胞活力有负面影响，并对其进行了进一步的药理学研究。流式细胞术显示，除A4外，所有样品的抗增殖活性模式为细胞周期阻滞和亚二倍体（亚G1）细胞积累。通过鸡胚绒毛尿囊膜（CAM）研究了它们的抗血管生成潜力，其中记录到血管内皮生长因子（VEGF）诱导的新生血管形成受到显著抑制（p < 0.0001）。通过小鼠海绵植入法在体内证实了该效果。这些发现表明，睡茄根具有细胞周期破坏和抗血管生成活性，这可能是其抗癌作用的关键介质。