The improvement effect of nanpao, a kampo medicine, on the age-related decline in reproductive function was evaluated in female rats given the test drug for a long-term period. Young rats were allocated to the cesarean section and natural delivery groups to examine reproductive performance (young rat groups). Five-month-old rats were allocated to the 3 groups (aged rat groups): 1--control and 2--nanpao-treated groups. They were given orally in a dose of 0, 30 or 100mg/kg/day of the test drug, respectively. In aged rats, the first mating experiment was initiated at week 21 of dosing to evaluate reproductive performance by natural delivery and the second mating experiment at week 31 of dosing was evaluated by cesarean section. In the first and second mating experiments, various reproductive functions decreased in aged rats as compared to the young rats. On the other hand, loss of regular estrous cycles, decreases in delivery and pregnancy rates and mean fetal weights were inhibited in the treated groups as compared to the control group. In addition, decreases in the numbers of mean live offspring and fetuses were inhibited in the 100 mg/kg/day group. In conclusion, nanpao maintained normal embryo-foetal development in female rats.

The present study was designed to evaluate the time-dependent effects of Nanpao, a kampo medicine, on age-related changes in the estrous cycle of female rats, and to investigate the utility of measuring electrical impedance in the vagina (EIV) for studying transitional changes in the estrous cycle. Rats were allocated to 3 groups: control, Nanpao 30 mg/kg/day, and 100 mg/kg/day groups. EIV measurements and cytology samples were taken for 14 days at the age of 6 months before the initial treatment. After the start of the treatment, these data were collected at about monthly intervals until the age of 10 months in the same manner. Observations at the ages of 7 (weeks 2-3 of dosing) and 8 months (weeks 6-7 of dosing) showed that loss of a regular estrous cycle in the 100 mg/kg/day group was inhibited as compared to the control group. Moreover, at the ages of 9 (weeks 11-12 of dosing) and 10 months (weeks 17-18 of dosing), these effects were identified not only in the 100 mg/kg/day group, but also in the 30 mg/kg/day group. Since vaginal cytology and EIV gave almost concordant results as indicators of estrous cyclicity, we concluded that the measurement of EIV was capable of detecting time-dependent changes in the estrous cycle as well as observations of vaginal smears. A short period of Nanpao administration inhibited loss of regular estrous cycles, and the EIV method is a worthwhile approach to a more precise study of estrous cyclicity in rats exhibiting abnormal estrous cycles.

Abstract:The effects of long-term treatment with Nanpao, a kampo medicine, on cold constitution were evaluated in aged female rats. Five-month-old rats were administered Nanpao orally at doses of 0, 30, or 100 mg/kg/day. The peripheral blood flow and surface skin temperature in the hind paws were measured using a laser Doppler blood flow meter and infrared thermography, respectively. In animals treated with Nanpao, the peripheral blood flow increased dose-dependently compared to that in the control group. Moreover, the surface skin temperature after immersion in ice-cold water was higher in the Nanpaotreated groups than in the control group at all measurement times. These results suggest that Nanpao has the potential to improve cold constitution associated with decreased peripheral blood flow in women.