Biology Reference
In-Depth Information
agrimoniin (Miyamoto
et al.
, 1985). Thereafter, a collaboration with
Okuda's group has led to the identification of a large number of related
tumoricidal ellagitannins.
6.2.1.1
Agrimoniin
Although agrimoniin (
61
, Fig. 6.11) had been known for some time,
since it had been isolated before from the
Rosaceae
plants
Agrimonia
pilosa
Ledeb,
Agrimonia japonica
(MIQ) KOIDZ, and
Potentilla
kleiniana
WIGHT
et
ARNOTT (Okuda
et al.
, 1984, 1982c), its
antitumor properties were not known before Miyamoto's work.
Agrimoniin, the first dimeric ellagitannin to be isolated and
characterized, significantly extended the life span of mice inoculated
with mammary carcinoma MM2 cells, and in some cases even led to
tumor regression. Agrimoniin was found to be effective upon either pre-
or posttreatment and showed an IC
50
of 2.6 μg/mL. In some preliminary
experiments, agrimoniin appeared to cause an enhancement in the
growth rate of macrophages, lymphocytes, and adherent peritoneal
exudate cells, as well as an enlargement of spleen size, observations
which supported the idea that tannins act as immunostimulators
(Miyamoto
et al.
, 1987a). Agrimoniin (at a 5 mg/kg dose) also was found
to be active in mice inoculated with sarcoma-180 by effecting a 75%
increase in the life span (%ILS) of the mice, but no tumor regressors out
of 6 mice were detected. An increase in dose to 10 mg/kg led to 3/6
cured mice and a 136 %ILS (Miyamoto
et al.
, 1993a). Agrimoniin has
been isolated from several other sources such as the rosaceous Chinese
medicinal plants
Rosa laevigata
MICHX,
Rosa davurica
Pall.,
Potentilla
erecta
L., and
Potentilla discolor
Bunge, the North America
Rosa
woodsii
Lindle, strawberry plants (cv. Jonsok), the fruit of
Rosa
taiwanensis
Nakai, and the Bolivian medicinal plant
Buddleia coriacea
Remy (Yoshida
et al.
, 1989a-c, Hukkanen
et al.
, 2007, Kubo
et al.
, 1995,
Feng
et al.
, 1996, Lin and Wang, 1998, Ito
et al.
, 2001, Lund and
Rimpler, 1985, Yoshida
et al.
, 1991). This compound also has diverse
biological activities including human neutriphil elastase (a serine
protease) inhibition (IC
50
0.9 μM), antileishmanial properties (EC
50
1.1
μg/mL), HIV-1 reverse transcriptase inhibition (IC
50
<0.88 μM), aryl
