Modulation of placental inflammation by Azadirachta indica in rat models of diabetes-induced maternal and fetal complications.

Maternal diabetes mellitus (MDM) is associated with an increased risk of fetal and placental malformations compared with normal pregnancies. The leaf extract of Azadirachta indica (neem) has been employed as a bioactive agent with proven antidiabetic potential. Beyond its hypoglycemic effects, neem extract has been reported to reduce inflammatory markers, ameliorate insulin resistance, and enhance blood circulation. In the present study, pregnant female rats were allocated into four experimental groups: (I) control (C), (II) neem-treated (N), (III) type 2 diabetes mellitus-induced (D), and (IV) diabetic pregnant rats treated with neem extract (D + N). Diabetic dams exhibited marked elevations in serum glucose, insulin, and lipid profile parameters. Moreover, a significant increase in IFN-γ and IFN-γ/IL-10 ratio, accompanied by a significant reduction in IL-10 levels, was recorded in comparison with controls. Treatment of diabetic dams with neem extract resulted in significant improvements in maternal body weight, reproductive performance, and fetal morphology relative to untreated diabetic rats. Histopathological examination of placental tissues revealed that neem supplementation normalized the decidual layer, increased its thickness, and enhanced the structure of the junctional zone (JZ) and labyrinth zone (LZ) compared to diabetic controls. In conclusion, administration of Azadirachta indica leaf extract demonstrated protective effects against diabetes-induced alterations in pregnancy. It improved maternal metabolic and inflammatory profiles, enhanced reproductive outcomes, and preserved the histological integrity of placental tissues in diabetic rats.