4.7 Article

The unique activity of saponin: Induction of cytotoxicity in HTLV-1 infected cells

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BIOORGANIC & MEDICINAL CHEMISTRY
卷 91, 期 -, 页码 -

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2023.117408

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Saponin; Akebia quinata Decaisne; Seeds; HTLV-1; Gag protein

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In this study, a natural compound extracted from Akebia quinata Decaisne fruit was found to kill HTLV-1-infected cells while not affecting uninfected cells. The active ingredients, Akebia saponins A and B, demonstrated cytotoxicity against both infected and uninfected cells. Akebia saponin C, with similar activity to the extract, exhibited selective cytotoxicity against HTLV-1 infected cells. These findings may have implications for the development of new therapies for infectious diseases.
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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