Induced termination of pregnancy by purified extracts of Azadirachta indica (Neem): Mechanisms involved

PROBLEM: To develop a self-administered, orally delivered method for abrogation of early pregnancy. METHOD: Use of purified Neem extracts containing immunomodulators stimulating Th-1 cells and macrophages; test animals, rats, baboons, and monkeys, onset of pregnancy confirmed by surgery and counting of implants on day 7 in rats and by chorionic gonadotropin (CG) and progesterone assays in primates; termination defined by complete resorption on day 15 in rats and by bleeding and decline of CG and progesterone in baboons. RESULTS: Pregnancy was terminated successfully in both rodents and primates with no significant side effects. Fertility was regained in both species after one or two irregular cycles. Progeny born had normal developmental landmarks and mothered normal litters in the course of time. The active principle in Neem has been partially fractionated by activity-guided purification. A cascade of events are involved in abrogation of pregnancy. In primates, a decrease in progesterone is an early event. A transient increase in CD4 and CD8 cells is noted in spleen at 96 hr and in mostly CD8 cells in mesenteric lymph nodes. Treatment causes an elevation of both immunoreactive and bioactive TNF-alpha and gamma-interferon in serum, mesenteric lymph nodes, and foetoplacental tissue. CONCLUSION: Immunomodulators of plant origin are potentially usable for termination of unwanted pregnancy.