Synergistic Differential DNA Demethylation Activity of Danshensu (Salvia miltiorrhiza) Associated with Different Probiotics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a major hepatic disorder occurring in non-alcohol-drinking individuals. Salvianic acid A or Danshensu (DSS, 3-(3, 4-dihydroxyphenyl)-(2R)-lactic acid), derived from the root of Danshen (Salvia miltiorrhiza), has demonstrated heart and liver protective properties. In this work, we investigated the antioxidant activity and hepatoprotective activity of Danshensu alone and in combination with different agents, such as probiotic bacteria (Lactobacillus casei and Lactobacillus acidophilus), against several assays. The inhibition mechanism of the methylation gene biomarkers, such as DNMT-1, MS, STAT-3, and TET-1, against DSS was evaluated by molecular docking and RT-PCR techniques. The physicochemical and pharmacokinetic ADMET properties of DSS were determined by SwissADME and pkCSM. The results indicated that all lipid blood test profiles, including cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were reduced after the oral administration of Danshensu combined with probiotics (L. casei and L. acidophilus) that demonstrated good, efficient free radical scavenging activity, measured using anti-oxidant assays. ADMET and drug-likeness properties certify that the DSS could be utilized as a feasible drug since DSS showed satisfactory physicochemical and pharmacokinetic ADMET properties.

A study of roflumilast treatment on functional and structural changes in hippocampus in depressed Adult male Wistar rats.

Depression is a common stress disability disorder that affects higher mental functions including emotion, cognition, and behavior. It may be mediated by inflammatory cytokines that interfere with neuroendocrine function, and synaptic plasticity. Therefore, reductions in inflammation might contribute to treatment response. The current study aims to evaluate the role of Protein Kinase (PKA)- cAMP response element-binding protein (CREB)- brain derived neurotropic factor (BDNF) signaling pathway in depression and the effects of roflumilast (PDE4 inhibitor) as potential antidepressant on the activity of the PKA-CREB-BDNF signaling pathway, histology, and pro-inflammatory cytokine production. Forty Adult male Wistar rats were divided into 4 groups: Control group, Positive Control group: similar to the controls but received Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment, Depressed group which were exposed to chronic stress for 6 weeks, and Roflumilast-treated group which were exposed to chronic stress for 6 weeks and treated by Roflumilast (3 mg / kg / day) by oral gavage for the last 4 weeks of the experiment. The depressed group showed significant increase in immobility time with significant decrease in swimming and struggling times, significant decrease in hippocampal PKA, CERB, BDNF, Dopamine, Cortisone, and Superoxide dismutase while hippocampal Phosphodiesterase-E4, Interleukin-6, and Malondialdhyde levels were significantly elevated. These findings were significantly reversed upon Roflumilast treatment. Therefore, it could be concluded that depression is a neurodegenerative inflammatory disease and oxidative stress plays a key role in depression. Roflumilast treatment attenuated the depression behavior in rats denoting its neuroprotective, and anti-inflammatory effects.

The Protective effects of Vitamin E against alterations of rat testis structure induced by deltamethrin; histological, ultrastructure, and biochemical study.

Deltamethrin is a widely used synthetic pyrethroid pesticide. It causes reproductive toxicity. Aim of the work: it evaluates the impact of vitamin E in restoration of the testicular integrity of albino rats after toxicity induced by Deltamethrin. Thirty-six adult male albino rats were included, and they were further sub-divided into four experimental groups; Group A: six rats served as controls. Group B (Model): 10 rats equally divided into two sub-groups (B1): the rats received deltamethrin dissolved in oil in a dose of 0.6 mg/kg/daily by nasogastric gavage for 2 weeks. (B2): the rats received Deltamethrin in the same dose of group B1 for 1 month. Group C (Protected): 10 rats equally divided into two sub-groups (C1): the rats received deltamethrin orally 0.6 mg/kg/day concomitant with Vitamin E dissolved in 1 ml of corn oil in a dose 200 mg/kg/day by nasogastric gavage for 2 weeks. (C2): the rats received deltamethrin concomitant with Vitamin E in the same dose of group C1 for 1 month. Group D (Treatment): 10 rats received deltamethrin for 1 month followed by Vitamin E for another month in the same previously prescribed doses. Significant decreases in serum testosterone level, GSH, catalase activity, and significant increase in MDA in the deltamethrin-treated group were detected. Moreover, histological and ultrastructural examinations of the testis seminiferous tubules showed detrimental alterations in the deltamethrin group which were duration dependent. Vitamin E administration reversed such alterations. Vitamin E ameliorates the testicular dysfunction caused by Deltamethrin.

Spirulina supplements: an approach moderating aspirin persuaded histological and ultra-structural alterations in albino rats gastric mucosa.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs. The pathogenesis of aspirin-induced gastric ulceration includes blocking the activities of the cyclooxygenase enzymes (COX-1 and COX-2) leading to reduced mucus and bicarbonate secretion. Spirulina contains many functional bioactive ingredients with antioxidant and anti-inflammatory activities, including phenolic phytochemicals and phycobiliprotein C-phycocyanin. To investigate the possible gastroprotective role of spirulina against aspirin-induced gastric mucosal insults. Forty adult male albino rats were randomly divided into four experimental groups. Group I (Control) and group II (Spirulina control) were given spirulina for 3 days, group III (Ulcer model) were given single dose of acetyl salicylic acid to induce ulcer and group IV (Treatment) were given spirulina for 3 days after induction of ulcer formation. Animals were sacrificed, stomachs were collected and processed for examination of light and scanning electron microscope histopathological examination. Statistical difference mucosal mucin area percentage among groups was determined and data were analyzed. Histological examination of the H&E-stained and combined Alcian-blue-PAS-stained sections of Group III rats illustrated severe destruction of the mucosal architecture and reduction of the mucin surface area while those examined for group IV illustrated minor affection of the gastric mucosa and mucin protective layer. Oxidant antioxidant markers: Nitric oxide (NO) is elevated, Glutathione (GSH) and superoxide dismutase (SOD) are reduced in aspirin treated group. The use of Spirulina restores the normal balance between the oxidant antioxidant system. Spirulina has a great potential in protecting the gastric mucosa against harmful effect of NSAID.

Sitagliptin's renoprotective effect in a diabetic nephropathy model in rats: The potential role of PI3K/AKT pathway.

Management of diabetic nephropathy (DN) is far from satisfactory. There is a rising role of the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway in the pathogenesis of DN. This study aimed at investigating the renoprotective effects of PI3K/AKT pathway via sitagliptin in a rat model of DN. Thirty-two male Wistar rats were divided into four groups (eight rats each): (I) control, (II) sitagliptin, (III) DN, and (IV) DN + sitagliptin. Fasting blood glucose (FBG), kidney index, and kidney function tests in both blood and urine were measured. The levels of superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-ß) and gene expressions of PI3K, pPI3K, AKT, and pAKT in renal tissue were detected. Renal histopathological and immunohistochemical studies were evaluated. DN + sitagliptin group showed significant decrease in FBG and kidney index, improvement in kidney function tests, and a decrease in levels of TNF-α and TGF-ß in renal tissues compared with DN group. This was associated with significant increase in SOD and gene expressions of PI3K and AKT and their phosphorylated active forms in renal tissue in DN + sitagliptin group compared with DN group. Moreover, DN + sitagliptin group showed apparent decrease in amount of collagen fibers and expression of alpha-smooth muscle actin (α-SMA) compared with DN group. This work shows that sitagliptin improved renal functions and histopathological changes, impeded inflammation, and oxidative stress and upregulated PI3K/AKT pathway which highlights its renoprotective effects in a rat model of DN.

Effect of caffeinated energy drinks on the structure of hippocampal cornu ammonis 1 and dentate gyrus of adult male albino rats.

Energy drinks are available worldwide and frequently consumed to increase energy level and compensate lack of sleep. Energy drinks consumers aim to improve their cognitive functions. Red Bull is the most popular energy drink consumed in Egypt. However, the link between the impact of energy drinks on the structure of hippocampal cornu ammonis 1 (CA1) and dentate gyrus (DG), a highly vulnerable brain regions to various insults, has not yet documented. To study the effect of energy drinks on structure of hippocampal CA1 and DG of adult male albino rats. Twenty one adult male albino rats were divided into three groups; group I control group, groups II and III received Red Bull, with a dose of 3.75 ml/kg/day orally using gastric tube for four and eight consecutive weeks respectively. At the end of the experiment, brains were dissected and hippocampal specimens were processed for histopathological and immunohistochemical studies. Histopathological examination of hippocampal sections in group II revealed vacuoles, decrease thickness of pyramidal cell layer with irregular dark or ghost nuclei. However, changes were more severe in group III with cracks in pyramidal cell layer, massive vacuolation and signet ring cells. Moreover, star shaped astrocytes and glial fibrillary acidic protein immuno-reactivity were more abundant in group III than in group II. Caffeinated energy drinks produced neurodegenerative changes and reactive astrocytosis in hippocampal CA1 and DG of adult male albino rats. These changes were duration-dependent being more severe in longer duration of intake.