Fukuoka University, Jonan-ku, Fukuoka, Japan.
J Nat Med. 2011 Jul;65(3-4):559-67. doi: 10.1007/s11418-011-0543-9. Epub 2011 May 14.
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). Clinical manifestations of ATL range from smoldering to chronic, lymphoma and acute subtypes. Patients with acute and lymphoma-type ATL require therapeutic intervention. Conventional chemotherapeutic regimens used against other malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute and lymphoma-type ATL remain very poor. In this study, 214 extracts from 162 plants belonging to 65 families were screened for the purpose of elucidating the anti-proliferative effect against HTLV-1-infected T-cell lines. Extracts from aerial parts of Physalis pruinosa showed potent inhibitory effect. We isolated five withanolides from the extracts by activity-guided fractionation and examined the structure-activity relationships. The presence of a 5β,6β-epoxy function is suggested to be essential for the activity, and the most active principle showed selective toxicity to HTLV-1-infected T-cell lines.
成人 T 细胞白血病/淋巴瘤（ATL）是一种由人类 T 细胞嗜淋巴细胞病毒 I 型（HTLV-1）引起的外周 T 细胞恶性肿瘤。ATL 的临床表现从低热到慢性、淋巴瘤和急性亚型不等。急性和淋巴瘤型 ATL 患者需要治疗干预。针对其他恶性淋巴瘤使用的常规化疗方案已用于 ATL 患者，但急性和淋巴瘤型 ATL 的治疗效果仍然很差。在这项研究中，为了阐明对 HTLV-1 感染的 T 细胞系的抗增殖作用，从 65 个科的 162 种植物的 214 种提取物中进行了筛选。来自酸浆属植物地上部分的提取物表现出强烈的抑制作用。我们通过活性导向分离从提取物中分离出五种乌头原碱，并检查了结构-活性关系。存在 5β,6β-环氧功能被认为是活性所必需的，最活跃的原理对 HTLV-1 感染的 T 细胞系显示出选择性毒性。
