Anti-depressant effect of Naringenin-loaded hybridized nanoparticles in diabetic rats via PPARγ/NLRP3 pathway.

Naringenin (NAR) has various biological activities but low bioavailability. The current study examines the effect of Naringenin-loaded hybridized nanoparticles (NAR-HNPs) and NAR on depression induced by streptozotocin (STZ) in rats. NAR-HNPs formula with the highest in vitro NAR released profile, lowest polydispersity index value (0.21 ± 0.02), highest entrapment efficiency (98.7 ± 2.01%), as well as an acceptable particle size and zeta potential of 415.2 ± 9.54 nm and 52.8 ± 1.04 mV, respectively, was considered the optimum formulation. It was characterized by differential scanning calorimetry, examined using a transmission electron microscope, and a stability study was conducted at different temperatures to monitor its stability efficiency showing that NAR-HNP formulation maintains stability at 4 °C. The selected formulation was subjected to an acute toxicological test, a pharmacokinetic analysis, and a Diabetes mellitus (DM) experimental model. STZ (50 mg/kg) given as a single i.p. rendered rats diabetic. Diabetic rat groups were allocated into 4 groups: one group received no treatment, while the remaining three received oral doses of unloaded HNPs, NAR (50 mg/kg), NAR-HNPs (50 mg/kg) and NAR (50 mg/kg) + peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662 (1mg/kg, i.p.) for three weeks. Additional four non-diabetic rat groups received: distilled water (normal), free NAR, and NAR-HNPs, respectively for three weeks. NAR and NAR-HNPs reduced immobility time in forced swimming test and serum blood glucose while increasing serum insulin level. They also reduced cortical and hippocampal 5-hydroxyindoeacetic acid, 3,4-Dihydroxy-phenylacetic acid, malondialdehyde, NLR family pyrin domain containing-3 (NLRP3) and interleukin-1beta content while raised serotonin, nor-epinephrine, dopamine and glutathione level. PPAR-γ gene expression was elevated too. So, NAR and NAR-HNPs reduced DM-induced depression by influencing brain neurotransmitters and exhibiting anti-oxidant and anti-inflammatory effects through the activation PPAR-γ/ NLRP3 pathway. NAR-HNPs showed the best pharmacokinetic and therapeutic results.

Sourdough bread as nutritional intervention tool for improvement of cognitive dysfunction in diabetic rats.

BACKGROUND: The current research targeted to study the impact of nutritional intervention by two sourdough breads in improvement of cognitive dysfunction in diabetic rats. METHODS: Type-2 diabetes was induced in rats by Streptozotocin-Nicotinamide (STZ-NC). Diabetic rats were fed on balanced diet or balanced diet containing 20% of sourdough bread I or II for a month. Lipid profile, oxidative stress, inflammatory markers and cognitive functions were assessed in all rats. Gene expression of brain-derived neurotrophic factor (BDNF) and nuclear respiratory factor 2 (NRF-2) were assessed in hippocampal tissue, while expression of phosphoenol pyruvate carboxy kinase (PEPCK), and glucose transporter 2 (GLUT2) genes were evaluated in hepatic tissue. Chemical composition and fatty acids profile were evaluated in the prepared sourdough bread. RESULTS: Sourdough bread II showed higher content of phenolic compounds, fat, fiber and carbohydrates. Fatty acids profile revealed that sourdough bread I was higher in saturated fatty acids (16.08%), while sourdough bread sample II was higher in unsaturated fatty acids (79.33%). Sourdough bread I or II feeding rats' showed significant improvement in hyperglycemia, oxidative stress markers, inflammatory markers, lipid profile, liver and kidney functions in association with improvement in cognitive function. Gene expression of BDNF and NRF2 in hippocampal tissue were increased significantly, while hepatic GLUT2 and PEPCK gene expression were down-regulated in diabetic given sourdough bread I or II. CONCLUSION: Sourdough bread II was superior in all the studied parameters. The anti-diabetic effect and protection from cognitive dysfunction of sourdough bread samples may be ascribed to the occurrence of dietary fibers, phenolic compounds, and polyunsaturated fatty acids.

Chrysin loaded nanovesicles ameliorated diabetic peripheral neuropathy. Role of NGF/AKT/GSK-3ß pathway.

Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3ß (GSK-3ß) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3ß pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs.

Promoting weaning practices and growth of Egyptian infants by using communication for behavioral development approach.

BACKGROUND: Access to various affordable and nutritious foods is considered a challenging factor for households with limited resources affecting the proper weaning practices. In order to motivate communities to adhere to the right and proper weaning practices, the social aspect should be considered through close communication with the targeted communities. This study aimed to evaluate how impactful the use of the principles of Communication for Development (C4D) that respect parents' beliefs and their cultural norms is in improving the weaning practices and growth of infants in an Egyptian village. METHODS: An interventional three-phase study was conducted for three years. The intervention targeted 464 mothers of infants up to 2 years of age. C4D interventions encouraged each mother to provide her baby with nutritious and varied options through age-appropriate introduction and diversification of nutrient-rich complementary foods under the slogan " enjoy meals like a baby". The effectiveness of the approach was measured by five essential weaning practices: Introduction of solid, semi-solid, or soft foods, Minimum dietary diversity, minimum meal frequency, Minimum acceptable diet, and consumption of iron-rich foods. RESULTS: There was marked and significant improvement in the awareness and of the majority of the weaning practices' indicators as a result of the interventions. This was noticed for the timely introduction of complementary foods which increased from 36.7% to 82.0%, the minimum meal frequency indicator (3-5) which increased from 25.3% to 67.3%, iron-rich or fortified food (68.0% to 82%) as well as a regular checkup for baby health at the health unit (71.3%). Indicators that were improved but failed to achieve the target were the "Minimum Dietary Diversity" (reached 32%) and the minimum acceptable diet (reached 22.0%). A significant effect on linear growth especially for females is evidenced by the remarkable decrease in wasting (from 31.5% to 11.1%) and obesity (from 12.0% to 0%) associated with a considerable decrease in underweight (from 40% to 16.7%). CONCLUSION: Targeting caregivers through the C4D approach have succeeded in providing them with the support required for the provision of adequate nutrition for their infants that had significantly marked improvement in growth indices of their infants.

Basil Essential Oil and Its Nanoemulsion Mitigate Non Alcoholic Steatohepatitis in Rat Model with Special Reference to Gut Microbiota.

The present research evaluated the protective effect of basil essential oil nanoemulsion (BNO) and its parent basil essential oil (BO) towards steatohepatitis. Chemical composition of BO was assessed followed by formulation into different BNOs using the low energy spontaneous emulsification technique. An ideal formula of BNO was selected among the others based on its ultra-fine particle size (15.42 nm) and physical stability at 25-37°C, which was then tested in steatohepatitis rat model along with BO. Rats were divided into four groups, the first was fed on balanced diet (C), and the other groups were maintained on high fructose saturated fat diet deficient in choline to induce steatohepatitis, one of such groups served as control steatohepatitis (SC), the other groups received daily oral dose of BO and BNO, respectively. Microbiota (Firmicutes and Bacteroidetes) were counted in colon content and their ratio (F/B) was calculated. Liver fat, plasma lipid profile, plama interlukin-6, plasma lipopolysaccharides and plasma and colon content of lipocaline were assessed with histopathological examination of liver and colon. Results showed that the major volatile components of BO were linalool (60.9 %), eugenol (5.1 %) and eucalyptol (9.5%). SC group exhibited significant increase in liver lipids, plasma triglycerides, total cholesterol (TC), low density lipoprotein cholesterol and significant reduction in high density lipoprotein-cholesterol (HDL-C) compared to C group. Significant increase in plasma TC/HDL-C, interlukin-6, and lipocaline and F/B ratio and lipocaline in colon content were demonstrated in SC group without changes in plasma lipopolysaccharides compared to C. Histopathology of SC group showed liver fatty degeneration and fibroblasts activation while the colon demonstrated erosion and mucosal epithelium detachment. Treatment with either BNO or BO showed improvement compared to SC group. BNO was superior in reducing F/B ratio, liver lipids and histopathological changes. BO was more efficient in reducing TC, triglycerides and low density lipoprotein cholesterol. It is concluded that BO and BNO reduced the progression of nonalcoholic steatohepatitis in rat model. Gut microbiota in relation to steatohepatitis and related new therapies needs further investigations.

Induction of COX-1, suppression of COX-2 and pro-inflammatory cytokines gene expression by moringa leaves and its aqueous extract in aspirin-induced gastric ulcer rats.

The Moringa plant (Moringa oleifera) is known for its potential medicinal properties and health benefits in addition to its high nutritional value. The current study aimed to investigate the antiulcer effect of moringa leaves and its aqueous extract on pro-inflammatory cytokines and inflammatory mediators in ulcerative rats. Rats were treated with either moringa leaves (10%) or moringa extract (300 mg/kg body weight) for 4 weeks then treated with a single dose of aspirin to induce gastric ulcer. Moringa leaves and its extract markedly reduced ulcer index, gastric volume and total acidity. Both treatments induced a significant increase in gastric mucosal mucin content and plasma NO level associated with significant decrease in plasma TNFα. Moringa leaves and its extract prompted down-regulation of TNFα, TGFß1 and COX2 genes expression by 2.7, 3.5, and 8.4 fold-change for moringa leaves and 2.7, and 2.3, 4.1 fold-change for moringa extract, respectively. Moringa leaves and extract treatments altered the COX-1 gene expression levels to near normal values. This study confirms the gastro-protective influence of moringa leaves and its extract on aspirin-induced ulcer in rats as manifested by its significant reduction in inflammatory cytokines and normalization of gastric mucosal mucin and NO level. Overall, moringa leaves powder is more efficient as antiulcer agent than moringa extract.

Determination of lignans, phenolic acids and antioxidant capacity in transformed hairy root culture of Linum usitatissimum.

Hairy root culture is a promising alternative method for the production of secondary metabolites. In this study, transformed root of Linum usitatissimum was established using Agrobacterium rhizogenes A4 strain from root cultures for lignans, phenolic acids and antioxidant capacity determination. Total lignin content (secoisolariciresinol diglucoside, secoisolariciresinol and matairesinol) was 55.5% higher in transformed root cultures than in the non-transformed root culture. Secoisolariciresinol was detected in higher concentration (2.107 µmol/g DM) in the transformed root culture than non-transformed culture (1.099 µmol/g DM). Secoisolariciresinol diglucoside and matairesinol were exclusively detected in the transformed root culture, but were not found in the non-transformed root culture. The overall production of phenolic acids in transformed roots was approximately 3.5 times higher than that of the corresponding non-transformed culture. Free radical scavenging DPPH˙ and ABTS˙+ assays showed 2.9-fold and 1.76-fold higher anti-oxidant activity in transformed root culture as compared to non-transformed.

Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer.

High dietary lignan exposure is implicated in a reduced breast cancer risk in women. The bacterial transformation of plant lignans to enterolignans is thought to be essential for this effect. To provide evidence for this assumption, gnotobiotic rats were colonized with the lignan-converting bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis (LCC rats). Germ-free rats were used as the control. All animals were fed a lignan-rich flaxseed diet and breast cancer was induced with 7,12-dimethylbenz(a)anthracene. The lignan secoisolariciresinol diglucoside was converted into the enterolignans enterodiol and enterolactone in the LCC but not in the germ-free rats. This transformation did not influence cancer incidence at the end of the 13 weeks experimental period but significantly decreased tumor numbers per tumor-bearing rat, tumor size, tumor cell proliferation and increased tumor cell apoptosis in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERs) α, ERß and G-coupled protein 30. The same was true for IGF-1 and EGFR involved in tumor growth. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione and malondialdehyde, considered as oxidative stress markers, did not differ between the groups. In conclusion, our results show that the bacterial conversion of plant lignans to enterolignans beneficially influences their anticancer effects.