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藤黄果提取物的体内毒性和抗肿瘤活性。

In vivo toxicity and antitumor activity of mangosteen extract.

机构信息

Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, 812-8582, Japan.

出版信息

J Nat Med. 2013 Apr;67(2):255-63. doi: 10.1007/s11418-012-0673-8. Epub 2012 May 24.

DOI:10.1007/s11418-012-0673-8
PMID:22622784
Abstract

Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.

摘要

山竹( Garcinia mangostana )在泰国传统医学中被广泛用于治疗各种疾病,尤其是消化系统疾病和感染。许多报道表明,山竹的粗提取物和活性成分对许多癌细胞系具有抗增殖作用。因此,本研究旨在提供山竹体内抗肿瘤活性的证据。本研究使用山竹果皮的甲醇粗提取物( CME ),其中包括 25.19%的 α-倒捻子素作为一种活性的黄烷酮。初步评估 CME 对 NL-17 鼠结肠癌细胞系的抑制肿瘤细胞增殖活性,基于 WST-1 和 LDH 测定法,其 IC50 值分别为 17 和 84μg/ml。通过使用雌性 BALB/c 小鼠进行体内毒性研究,评估了用于动物应用的安全剂量。急性毒性显示 LD50 值和近似致死剂量为 1000mg/kg,而短期研究的合适剂量应≤200mg/kg。CME 的抗肿瘤活性有效剂量在 100 至 200mg/kg 之间,肿瘤大小减少 50-70%。组织学染色清楚地表明,在剂量依赖性方式下,跖垫中的肿瘤细胞密度降低。CME 治疗的荷瘤小鼠的中位生存时间和寿命显著延长。本研究表明 CME 具有强大的抗肿瘤活性。因此,值得进一步研究以鉴定活性化合物并深入了解其机制,从而获得新型有效的抗癌药物。

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