RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD). MATERIALS AND METHODS: Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed. RESULTS: Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats. CONCLUSION: Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.
Assuntos
Azadirachta , Desenvolvimento Fetal/efeitos dos fármacos , Glicerídeos/efeitos adversos , Limoninas/efeitos adversos , Terpenos/efeitos adversos , Animais , Diabetes Mellitus Experimental/metabolismo , Feminino , Reabsorção do Feto , Teste de Tolerância a Glucose , Metabolismo dos Lipídeos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Gravidez , Resultado da Gravidez , Gravidez em Diabéticas/metabolismo , Ratos , SementesRESUMO
The 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), isolated from extracts of Melia azedarach L., displays antiviral and immunomodulating properties. CDM is the first reported tetranortriterpenoid responsible for the alkalinization of intracellular compartments affecting both, viral endocytic and exocytic pathways. Considering that viral glycoprotein synthesis is completely dependent upon cellular membrane trafficking, we questioned whether CDM might also interfere with the normal transport of cellular glycoproteins. This study demonstrates that CDM promoted a transient block in the transport of two cellular glycoproteins, the transferrin receptor (TfR) and TNF-alpha. Nevertheless, CDM did not affect the transferrin binding ability of TfR and did not impede the TNF-alpha secretion. On the other hand, CDM disturbed the intracellular localization of capsid, glycoprotein and tegument proteins simultaneously in the same HSV-1 infected cells. Besides, we show that concanamycin A and monensin provoke a permanent blockage of viral and cellular glycoproteins, in contrast to the delay observed after CDM treatment. Thus, the delay on glycoprotein transport caused by CDM would account for the strong inhibition on virus multiplication without interfering with the bioactivity of cellular glycoproteins.