Indian monks consumed the juice of fresh green neem leaves to suppress sexual desire.⁷ Neem leaf and leaf oil are used traditionally as an insecticide,^5,8 but the main insecticidal activity is found in the seeds.

Neem leaf contains limonoids (including aradirachtins) and simple terpenoids.¹⁰ Limonoids are modified triterpenes.

• Oral administration of neem leaf extract reduced blood sugar levels in normal and streptozocin-induced diabetic models.¹¹ The hypoglycemic effect was comparable to glibenclamide (an antidiabetic drug).¹² Pretreatment with neem leaf prevented the rise in blood glucose levels compared with control diabetic animals.¹² Neem leaf extract demonstrated an antihyperglycemic effect against glucose and epinephrine (adrenaline)-induced models of hyperglycemia¹³ and blocked the peripheral utilization of glucose and the glycogenolytic effect of epinephrine in normal and diabetic experimental models.¹⁴

• The anxiolytic activity of neem leaf extract (up to 200 mg/kg) was comparable to that induced by diazepam (1 mg/kg) after oral administration.¹⁵ Neem leaf extract demonstrated analgesic¹⁶ and sedative¹⁷ activity in vivo after intraperitoneal administration.

• After oral administration, the water-soluble portion of an alcohol extract of neem leaf exhibited antiinflammatory activity in the cotton pellet granuloma assay.²⁰ Dose-dependent antiinflammatory activity was also demonstrated in carrageenan-induced acute inflammation (oral²¹ and intraperitoneal²² routes) and formaldehyde-induced subacute inflammation (oral route).²¹

• An aqueous extract of neem leaf augmented both humoral and cellmediated immune responses after oral administration,²³ enhanced phagocytic activity of macrophages both in vitro and in vivo, and induced expression of MHC-II antigens on macrophages.²⁴ Neem leaf (2 g/kg, orally) enhanced antibody titers against Newcastle disease virus antigen in chickens that had survived an outbreak of infectious bursal disease.²⁵

• Neem leaf extract demonstrated an inhibitory action against a wide spectrum of microorganisms in vitro, including protozoa (Plasmodium falciparum),^26,27 viruses,^28–30 bacteria³¹ and fungi.^32,33 The in vivo activity of neem leaf extract against mouse plasmodia was not convincing.¹

• A methanol extract of neem leaf exhibited direct antimutagenic activity in vitro.³⁵ An aqueous extract inhibited cyclophosphamide- and mitomycin-induced chromosomal aberrations after intraperitoneal administration³⁶ and inhibited chemically induced oral squamous cell carcinomas after oral administration.³⁷

• Histopathologic studies confirm that oral administration of an aqueous extract of neem leaf protected against increases in serum liver enzymes induced by acetominophen (paracetamol).^38,39 This finding demonstrates hepatoprotective activity.

• Neem leaf extract given orally at the early postimplantation stage terminated pregnancy in rodents and primates.⁴¹ Oral administration of aqueous neem leaf extract demonstrated antifertility activity in male mice.⁴² Neem leaf powder by the oral route resulted in reversible atrophic and biochemical changes in male reproductive tissue in vivo.^43–45

• Morphologic changes in spermatozoa have been observed in rats treated with powdered neem leaf, which may be the result of an antiandrogenic effect.⁴⁶ Oral administration of a neem leaf aqueous extract decreased serum testosterone but did not affect the fertility index in male rats. After intraperitoneal administration, a neem leaf fraction containing predominately steroidal compounds impaired spermatogenesis and altered the morphology and motility of sperma-tozoa, leading to a reduced fertility index.⁷ However, in another study, neem leaf extract was not observed to interfere with spermatogenesis in male rats fed the extract, but antiimplantation and abortifacient effects were observed in females mated by these males.⁴⁷