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

Wataru Shida; Yurika Tahara; Saki Morikawa; Kazuaki Monde; Ryoko Koga; Takeo Ohsugi; Masami Otsuka; Atsushi Ikemoto; Hiroshi Tateishi; Tsuyoshi Ikeda; Mikako Fujita

doi:10.1016/j.bmc.2023.117408

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

Bioorg Med Chem. 2023 Aug 15:91:117408. doi: 10.1016/j.bmc.2023.117408. Epub 2023 Jul 7.

Authors

Affiliations

¹ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan.
² Department of Microbiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto 860-8556, Japan.
³ Department of Laboratory Animal Science, School of Veterinary Medicine, Rakuno-Gakuen University, 582 Bunkyodai-midorimachi, Ebetsu, Hokkaido 069-8501, Japan.
⁴ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan; Department of Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto, Kumamoto 862-0976, Japan.
⁵ Division of Regional Studies and Clinical Psychology, Faculty of Education and Human Studies, Akita University, 1-1 Tegatagakuen-machi, Akita, Akita 010-8502, Japan.
⁶ Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, Kumamoto 860-0082, Japan. Electronic address: tikeda@ph.sojo-u.ac.jp.
⁷ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, Kumamoto 862-0973, Japan. Electronic address: mfujita@kumamoto-u.ac.jp.

PMID: 37453188
DOI: 10.1016/j.bmc.2023.117408

Abstract

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, P_K 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.

Keywords: Akebia quinata Decaisne; Gag protein; HTLV-1; Saponin; Seeds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases
Cell Line
Human T-lymphotropic virus 1*
Humans
Jurkat Cells
Plant Extracts
Saponins* / pharmacology

Substances

Plant Extracts
Saponins
N-succinyl-l,l-diaminopimelic acid desuccinylase
Amidohydrolases