Evaluation of Anti-fertility Potential of Selected Medicinal Plants of Tana River County, Kenya.

Abstract

Approximately 200 million women in the developing world have unmet contraceptive need. Globally 20 million women procure unsafe abortions yearly due to the unmet contraceptive need. In Kenya; 465000 unsafe abortions were carried out in 2012 largely due to unplanned pregnancies. Conventional contraceptives though potent antifertility agents are not devoid of side effects. The search for novel affordable, reversible, safe and potent antifertility agents with minimal side effects is imperative. The overall objective of the study was to evaluate the anti-fertility properties of two selected medicinal plants (Croton menyharthii and Uvariodendron kirkii) in female Winstar rats. The study documented medicinal plants used for reproductive dysfunctions and also determined the pharmacological efficacy, phytochemical compounds, effect of extracts on reproductive parameters, reproductive hormonal profile and ovarian and uterine histomorphology of the selected plants. An ethnobotanical survey was carried out using questionnaires and focused group discussions. A total of 80 herbalists were interviewed. Pharmacological efficacy and phytochemical compounds of two most frequently mentioned plants namely Croton menyharthi and Uvariodendron kirkii were determined. The antifertility efficacy of the two plants on mating success, fertility index, gestation length, litter size and body weight was evaluated using 3 treatment regimes on normocyclic female winstar rats aged between 50-60 days. Cyclicity was monitored by daily vaginal smears and only rats with regular estrus cycles were used for the study. Male rats were introduced into female cages at the ratio of 1 male per 2 females at the appropriate time. A total of 96 rats were used. These were divided into 3 groups (1, 2 and 3) with 32 rats each. The 32 rats in each group were further divided into 4 subgroups (A, B, C, D) with 8 rats each. Group1, sub group A and B, received 500 and 800 mg/Kg of Croton menyharthii respectively. Subgroup C and D of group 1 received 500 and 800 mg/kg Uvariodendron kirkii respectively. These doses were administered for 14 days through intra-abdominal gavage after which they were mated. The first day of gestation was taken to be the day spermatozoa were detected in the vaginal smear under the light microscope. Group 2 animals were first mated after which sub group A and B received 500 and 800 mg/Kg of Croton menyharthii aqueous extract respectively and Subgroup C and D received 500 and 800 mg/Kg Uvariodendron kirkii respectively for 14 days. Group 3 sub group A, B, C and D were treated in a similar manner as group 1 except extract administration was continued after mating until end of gestation. Control groups consisted of eighteen negative control rats that received 0.5ml physiological saline through intra-abdominal gavage daily in 3 treatment protocols as in the experimental animals above. Six positive control rats received a subcutaneous injection of estrogen/ progesterone combination (15μg estradiol / 0.15 mg progestrin) once. Both negative and positive control animals were then mated. Gestation length, litter sizes as well as body weights of all animals were recorded. The effect of Croton menyharthii and Uvariodendron kirkii extracts on estrus cycle, implantation index, reproductive hormonal profiles, uterine and ovarian histomorphology was also carried out.The reproductive dysfunctions identified were pregnancy related complications, dysmenorrhea, menorrhagia, amenorrhea, oligomenorrhea, fibroids, infertility and fertility regulators in women. Forty eight plant species distributed in 40 genera and 29 families were documented as being important for the management of pregnancy related complications, menstrual disorders, infertility, fibroids and as fertility regulators. Thirteen (27.08%) plants were used to treat infertility and eleven plants (22.92%) were used as female fertility regulators. Uvariodendron kirkii and Croton menyharthii significantly disrupted the estrus cycle in rats. Both plant extracts caused a prolonged duration of metestrus (P<0.01) and diestrus (P< 0.001) phases compared to the control. There was a significant decline in estrus (P< 0.05) and proestrus (P<0.05) phases. The plant extracts caused a dose related significant reduction in fertility index and implantation index. Croton menyharthii at 500mg/Kg and Uvariodendron kirkii at 800mg/Kg caused a significant (P<0.05) prolongation of the gestation length compared to the control (22 ± 1). Uvariodendron kirkii and Croton menyharthii aqueous extracts caused a significant reduction in litter size in group 1 and 3 at both dose levels compared to negative control. Both plant extracts however caused a non-significant reduction in litter size in group 2 at both dose levels. Uvariodendron kirkii and Croton menyharthii caused a significant reduction in FSH levels compared to the negative control. 17β estradiol serum levels significantly reduced in treated groups compared to positive and negative controls in a dose dependent manner by Croton menyharthii and Uvariodendron kirkii extracts. Croton menyharthii caused an increase in LH levels however Uvariodendron kirkii caused a non-significant reduction in LH levels at 500 and 800 mg / Kg compared to the negative control. Progesterone levels significantly increased (P<0.01) in treated groups compared to negative controls in a dose dependent manner by both plant extracts. Ovarian histomorphometry was disrupted with a significant finding being the loss of ovum in all ovaries in a dose dependent manner. Croton menyharthii caused 18% (P< 0.05) and 48% (P<0.01) loss of ovum at 500 mg/Kg and 800mg/Kg respectively. Uvariodendron kirkii caused the most significant (P<0.001) percentage loss of ovum; 39% at 500mg/Kg and 67% at 800mg/Kg. The study has shown that Croton menyharthi and Uvariodendron kirkii have potential as anti-fertility agents. The reversible anti fertility properties of both plants should however be evaluated in laboratory animals