IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

SOME TRADITIONAL HERBAL MEDICINES 95
A single oral dose of 120 or 90 mg/kg bw aristolic acid given by gavage to Swiss
albino mice on gestation day 1 or 6 caused marked reduction in uterine weight and
increased concentrations of acid phosphatase and a decrease in alkaline phosphatase in
the uterus. A subcutaneous dose of progesterone (1 mg per mouse) on gestation days 5–8
with aristolic acid on gestation day 6 did not prevent the effects. The authors concluded
that aristolic acid did not appear to block hormone synthesis in the ovary (Pakrashi &
Ganguly, 1982).
Aristolic acid disrupted nidation in Swiss albino mice when given at a dose of
150 mg/kg bw on gestation day 1. The treatment did not affect tubal transport of eggs,
but affected implantation. In addition, it inhibited the increase in specific uterine alkaline
phosphatase activity of the uterus, which in control mice was about three-fold through
gestation days 4–6. Based on these results, it was inferred that aristolic acid interferes
with estrogenic conditioning of the uterus (Ganguly et al., 1986).
Studies of endocrine properties of aristolic acid revealed anti-estrogenic effects, as
the compound inhibited estrogen-induced weight increase and epithelial growth of the
uterus in immature female Swiss albino mice. Aristolic acid given on gestation day 1
caused total inhibition of implantation at 60 mg/kg bw and decreased implantation at
dose levels down to 15 mg/kg bw (43% reduction) (Pakrashi & Chakrabarty, 1978a).
The methyl ester of aristolic acid caused a 100% abortifacient effect when a single
oral dose of 60 mg/kg bw was administered to Swiss albino mice on gestation day 6 or
7. At a dose of 30 mg/kg bw, the effect was 40%. The 60-mg/kg bw dose caused 25%
and 20% reduction of fertility when given on gestation day 10 or 12, respectively. No
toxic effects were reported in the dams and no malformations were found in the offspring
(Pakrashi & Shaha, 1978).
Aristolic acid administered orally to rabbits on gestation day 9 caused 65% fetal loss
at a dose of 60 mg/kg bw and 80% fetal loss at 90 mg/kg bw (Pakrashi & Chakrabarty,
1978b).
In male mice, oral feeding of the water-soluble part of the chloroform extract of
A. indica at a dose of 75 mg/kg bw caused a marked decrease in the weight of the testes
(55%) and accessory genital organs. There were varying degrees of arrest of spermatogenesis
and nuclear degeneration in various germinal cell types. The treatment also
caused a decrease of approximately 30% in body weight. The effects on the male sex
organs may have been a result of non-specific toxicity (Pakrashi & Pakrasi, 1977).