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来自马銮(莪术属近似绿花莪术Roxb.)根茎的倍半萜对白血病细胞的细胞毒性及增殖抑制作用

Cytotoxicity and inhibition of leukemic cell proliferation by sesquiterpenes from rhizomes of Mah-Lueang (Curcuma cf. viridiflora Roxb.).

作者信息

Anuchapreeda Songyot, Khumpirapang Nattakanwadee, Rupitiwiriya Kawinnat, Tho-Iam Leelawat, Saiai Aroonchai, Okonogi Siriporn, Usuki Toyonobu

机构信息

Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, Tokyo 102-8554, Japan; Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.

Department of Pharmaceutical Science, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

出版信息

Bioorg Med Chem Lett. 2018 Feb 1;28(3):410-414. doi: 10.1016/j.bmcl.2017.12.029. Epub 2017 Dec 13.

Abstract

Curcuma cf. viridiflora Roxb., also known as Mah-Lueang in Thai, belongs to the Zingiberaceae family and is grown from rhizomes. The rhizome of the plant has been used for medicinal purposes, in particular, to treat paralysis in Thai traditional medicine. However, no biologically active compounds have been reported from Mah-Lueang yet. In this study, natural compounds were isolated from Mah-Lueang and structurally determined by spectroscopic methods, including electrospray ionization mass spectrometry and nuclear magnetic resonance. The four isolated compounds were identified as furanodiene (1), dehydrocurdione (2), germacrone-4,5-epoxide (3), and zedoarondiol (4). These sesquiterpenes were investigated for antileukemic activities against KG1a and Molt4 cells. Leukemic cell proliferation is regulated by the Wilms' tumor 1 (WT1) transcription factor. Compound 1 showed the strongest cytotoxicity against both KG1a and Molt4 cells. Noncytotoxic concentrations (20% inhibitory concentration values) of all compounds were able to decrease the WT1 protein expression and total cell numbers in both cell lines. The four compounds showed good inhibitory activities for WT1 protein expression. Compounds 3 and 4 showed excellent antileukemic activities for both cell lines. In summary, four sesquiterpene compounds with antileukemic activities against the KG1a and Molt4 cell lines were identified in Mah-Lueang extracts.

摘要

莪术(Curcuma cf. viridiflora Roxb.),在泰语中也被称为Mah-Lueang,属于姜科,通过根茎繁殖。该植物的根茎已被用于药用,特别是在泰国传统医学中用于治疗瘫痪。然而,尚未有关于Mah-Lueang生物活性化合物的报道。在本研究中,从Mah-Lueang中分离出天然化合物,并通过光谱方法(包括电喷雾电离质谱和核磁共振)确定其结构。分离出的四种化合物被鉴定为呋喃二烯(1)、脱氢莪术二酮(2)、吉马酮-4,5-环氧化物(3)和莪术二醇(4)。研究了这些倍半萜对KG1a和Molt4细胞的抗白血病活性。白血病细胞增殖受威尔姆斯瘤1(WT1)转录因子调节。化合物1对KG1a和Molt4细胞均表现出最强的细胞毒性。所有化合物的非细胞毒性浓度(20%抑制浓度值)均能降低两种细胞系中WT1蛋白表达和细胞总数。这四种化合物对WT1蛋白表达均表现出良好的抑制活性。化合物3和4对两种细胞系均表现出优异的抗白血病活性。总之,在Mah-Lueang提取物中鉴定出四种对KG1a和Molt4细胞系具有抗白血病活性的倍半萜化合物。

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