Biology Reference
In-Depth Information
1.7.2.1
Inhibition of mutagenicity of carcinogens
The mutagenicity of Trp-P-1 (
i.e.
, 3-amino-1,4-dimethyl-5
H-
pyrido[4,3-
b
]indole) and MNNG (
i.e.
, N-methyl-N'-nitro-N-nitrosoguanidine), and
also that of
N
-OH-Trp-P-2 (
i.e.
, 3-hydroxyamino-1-methyl-5H-pyrido[4,
3-b]indole), a directly-acting mutagen, were strongly inhibited by
ellagitannins from medicinal plants, such as geraniin, mallotusinic acid,
pedunculagin and agrimoniin, and also by (-)-epigallocatechin gallate
(EGCG). Since ellagic acid was found to inhibit the mutagenicity of
7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene
(B[a]p diol epoxide) and since it is produced by hydrolysis of
ellagitannins, variation of the antimutagenic activity of
Geranium
thunbergii
was investigated along the extraction of geraniin during which
its hydrolysis occurs. Interestingly, the results showed that after an initial
and rapid increase of the inhibitory effect on Trp-P-1 due to an increase
of the concentration of geraniin as a result of its extraction from the
plant, a marked downward modulation of that effect was observed due to
the hydrolysis of geraniin. An upward modulation of the inhibitory effect
on B[a]p diol epoxide occurred simultaneously due to the hydrolytic
release of ellagic acid from geraniin (Okuda
et al.
, 1984a).
1.7.2.2
Inhibition of tumor promotion
Tumor promotion is a much longer process than its initiation during the
two-stage chemical carcinogenesis, and its inhibition is therefore
regarded as an important objective in cancer prevention. The tumor
promotion on mouse skin by 12-
O
-tetradecanoylphorbol-13-acetate
(TPA), after initiation with dimethylbenz[a]anthracene (DMBA), was
significantly inhibited by ellagic acid and several ellagitannins isolated
from
Cowania mexicana
and
Coleogyne ramosissima
. These compounds
were also found to inhibit Epstein-Barr virus early antigen (EBV-EA)
activation induced by TPA. The TPA-induced ornithine decarboxylase
(ODC) activity and the TPA-stimulated hydroperoxide production were
inhibited by several ellagitannins and other polyphenols (Ito
et al
.,
1999b). Inhibitors of TNF-α
release nowadays constitute attractive
potential candidates for the development of cancer preventing strategies.
