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
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.