Monosodium glutamate (MSG) is a widespread flavor enhancer and stabilizer in manufactured or packaged foods that possess myriad adverse effects. This study aimed to evaluate the effect of MSG on placental progesterone receptors and fetal development. Thirty pregnant Wistar Albino rats were divided into three groups (ten/each). The control group (G1) gavaged distilled water only, low-dose treated group (G2) gavaged 3 g/kg MSG, and high-dose treated group (G3) gavaged 6 g/kg MSG from 1st to 18th days of gestation, and all pregnant rats were sacrificed on the 19th day of gestation. The effect of MSG on fetal weights, crown vertebral length (CVL), placental weight, placental ghrelin expression, and fetal skeleton examination were estimated. MSG induced a significant decrease in fetal weights, CVL lengths, placental weight, and ghrelin expression in both treatment groups compared to the control group. Several parts of the fetal skeleton showed incomplete ossification and delayed chondrification in which high-dose maternally treated fetuses were more affected. Many degenerative changes were detected in both maternal and fetal liver and kidney tissues in MSG-treated groups. Moreover, MSG caused a significant increase in serum ALT, ALP, and creatinine levels in pregnant rats’ blood. Serum progesterone was only elevated in G3 on the 19th day of gestation. This study showed that the administration of MSG during pregnancy adversely influences fetal growth and skeletal development and caused several biochemical and histological changes in the maternal and fetal liver and kidney tissues which assure the toxic and teratogenic effects of MSG.
This study assessed the effectiveness of an aqueous extract of Moringa Oleifera Lam. leaves (MOL) alone or in combination with praziquantel (PZQ) drug targeting–infected mice with Schistosoma mansoni-induced liver and spleen damage. Mice were divided into eight groups control mice group treated orally with saline. PZQ group: non-infected mice treated orally with 300 mg/kg bwt PZQ three consecutive days. MOL group: non-infected mice treated orally with 150 mg/kg bwt MOL extract for 15 days. PZQ/ MOL group: non-infected mice treated orally with 300 mg/kg bwt PZQ for three consecutive days and 150 mg/kg bwt MOL extract for 15 days. IF group: infected mice with 100 cercariae/mouse of the Egyptian strain of S. mansoni. IF/PZQ group infected mice with S. mansoni cercariae and treated orally with 300 mg/kg bwt PZQ for three consecutive days. IF/MOL group: infected mice with S. mansoni cercariae treated orally with 150 mg/kg bwt MOL extract for 15 days. IF/PZQ +MOL group: infected mice with S. mansoni cercariae treated orally with 300 mg/kg bwt PZQ for three consecutive days and 150 mg/kg bwt MOL extract for 15 days. Blood, liver, spleen, worm, and eggs were collected at the end of the experimental period. Treatment of infected mice with MOL and PZQ together significantly reduced the number of ova/g tissue and eliminated the parasites. In addition, the liver and spleen of infected mice showed less histopathological alteration and immunohistochemical expression of nuclear factor kappa β (NF-Kβ). We can conclude that MOL extract combined with PZ has a curative effect on S. mansoni infection and helped to lessen its pathological effects.
Exploring new inhibitors with good bioavailability and high selectivity for managing type 2 diabetes mellitus (T2DM) and its associated complications is a major challenge for research, academia, and the pharmaceutical industry. Protein tyrosine phosphatase-1B (PTP1B) arose as an important negative regulator in insulin signaling pathways associated with metabolic disorders, including T2DM and obesity. Novel neutral compounds with a benzene-sulfonamide scaffold were designed and synthesized based on structural- and ligand-based drug design strategies for fragment growth. Promising hits against PTP1B were identified through in vitro enzymology inhibition assay. Mechanistic aspects of the compound's different inhibition activities were rigorously investigated through molecular docking coupled with explicit dynamics simulations. Four identified hits, 3c, 8, 10a, and 11, with sub-micromolar PTP-1B IC50 and significant predicted pharmacokinetic and pharmacodynamic parameters, were further biologically evaluated for their anti-diabetic, anti-obesity, anti-inflammatory, and anti-oxidant effects in a high-fat diet (HFD) + streptozotocin (STZ)-induced T2DM rat model. All these hit compounds exhibited a significant anti-diabetic and anti-obesity effect and a significant efficacy in reducing oxidative stress and increasing anti-oxidant enzymes while reducing inflammatory markers. Improving compound potency was further highlighted by improving the pharmacokinetic profile of the most active compound, 10a, through nano formulation. Compound 10a nano formulation showed the most promising anti-diabetic and anti-obesity effects and a remarkable histopathological improvement in all organs studied.