皂苷的独特活性:诱导HTLV-1感染细胞的细胞毒性

IF 3.3 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2023-08-15 DOI:10.1016/j.bmc.2023.117408
Wataru Shida , Yurika Tahara , Saki Morikawa , Kazuaki Monde , Ryoko Koga , Takeo Ohsugi , Masami Otsuka , Atsushi Ikemoto , Hiroshi Tateishi , Tsuyoshi Ikeda , Mikako Fujita
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引用次数: 0

摘要

感染逆转录病毒人类t细胞白血病病毒1型(HTLV-1)有时会导致难以治愈的疾病。为了找到抗htlv -1的天然化合物,我们选择使用htlv -1感染的t细胞系MT-2进行筛选。根据我们的研究结果,阿克比亚奎纳塔果实的果肉/种子提取物可以杀死MT-2细胞,但对未感染病毒的Jurkat细胞系没有影响。为确定有效成分,从奎纳塔种子中分离得到7种含1 - 6个糖段的皂苷,并对其对两种细胞系的活性进行了研究。皂素a和b对两种细胞系的杀伤作用相似,皂素D、E、PK和G没有细胞毒性。木犀草皂苷C与筛选中发现的提取物具有相似的活性。发现该化合物可增强Gag聚集,诱导Gag的异常裂解,抑制病毒粒子释放,并优先杀死HTLV-1感染的细胞;然而,他们的关系仍然难以捉摸。我们的发现可能会导致基于去除全病毒感染细胞的传染病新疗法的发展。
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The unique activity of saponin: Induction of cytotoxicity in HTLV-1 infected cells

Infection with the retrovirus human T-cell leukemia virus type 1 (HTLV-1) sometimes causes diseases that are difficult to cure. To find anti-HTLV-1 natural compounds, we opted to screen using the HTLV-1-infected T-cell line, MT-2. Based on our results, an extract of the pulp/seeds of Akebia quinata Decaisne fruit killed MT-2 cells but did not affect the Jurkat cell line that was not infected with virus. To determine the active ingredients, seven saponins with one-six sugar moieties were isolated from A. quinata seeds, and their activities against the two cell lines were examined. Both cell lines were killed in a similar manner by Akebia saponins A and B. Further, Akebia saponins D, E, PK and G did not exhibit cytotoxicity. Akebia saponin C had a similar activity to the extract found in the screening. This compound was found to enhance Gag aggregation, induce the abnormal cleavage of Gag, suppress virion release, and preferentially kill HTLV-1 infected cells; however, their relationship remains elusive. Our findings may lead to the development of new therapies for infectious diseases based on the removal of whole-virus-infected cells.

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来源期刊
Bioorganic & Medicinal Chemistry
Bioorganic & Medicinal Chemistry 医学-生化与分子生物学
CiteScore
6.80
自引率
2.90%
发文量
413
审稿时长
17 days
期刊介绍: Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.
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