Macrophage-oriented cytotoxic activity of novel triterpene saponins extracted from roots of Securidaca inappendiculata

Citation
S. Yui et al., Macrophage-oriented cytotoxic activity of novel triterpene saponins extracted from roots of Securidaca inappendiculata, INT IMMUNO, 1(11), 2001, pp. 1989-2000
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOPHARMACOLOGY
ISSN journal
1567-5769 → ACNP
Volume
1
Issue
11
Year of publication
2001
Pages
1989 - 2000
Database
ISI
SICI code
1567-5769(200110)1:11<1989:MCAONT>2.0.ZU;2-X
Abstract
It is recognized that macrophages in peripheral tissues often proliferate u nder pathological conditions such as tumors, inflammation and atheroscleros is. Because the growth state of macrophages is believed to be a factor regu lating the pathological process of the diseases, substances that regulate m acrophage growth or,survival may be useful for disease control. In this pap er, we identified the activity inhibiting macrophage growth in a hot water extract of roots of Securidaca inappendiculata. The extract markedly inhibi ted macrophage colony-stimulating factor (M-CSF/CSF-1)-induced growth of ma crophages, whereas it exerted a less potent effect on growth of Concanavali n A (Con A)-stimulated thymocytes or M-CSF-stimulated bone marrow cells. Th e inhibition of macrophage growth was caused by a cytotoxic effect rather t han a cytostatic effect. Cell death was due to the induction of apoptosis, as judged by staining with terminal deoxynucleotidyl transferase-mediated d -UTP nick end labelling (TUNEL). The cytotoxic activity seemed to be specif ic to peripheral macrophages; it showed a weak effect on the growth and sur vival of tumor cell lines including a macrophage-like cell line, J-774.1. M oreover, the saponin fraction induced apoptotic cell death of macrophages o nly when they were stimulated by M-CSF; it did not affect the viability of macrophages cultured without M-CSF or with granulocyte/macrophage-CSF. We d etermined the structures of the two active triterpene saponin compounds in the fraction, named securioside A and securioside B having a 3,4-dimethoxyc innamic group which is essential for the cell death-inducing activity. They are believed to be the primary compounds of new drugs for the treatment of pathological states in which macrophage proliferation occurs. (C) 2001 Els evier Science B.V. All rights reserved.