Physiology and Pharmacology
Volume:23 Issue: 3, Sep 2019

The reduction of glycogen synthase kinase-3β protein level may correlate to the neuroprotective effects of antioxidant agents like caffeine. Therefore, we aimed to evaluate the impact of GSK-3β protein on neuroprotective effects of caffeine in the SHSY5Y cells exposed to beta-amyloid.

We incubated SHSY5Ycells with beta-amyloid 25–35 and caffeine (0.6 and 1mM) for 24h. Cell viability was determined using MTT test. We used the western blotting technique to measure the glycogen synthase kinase-3β and phosphorylated glycogen synthase kinase-3β protein levels.

Caffeine (0.6 and 1mM) diminished beta-amyloid neurotoxicity and attenuated the beta-amyloid effects on the glycogen synthase kinase-3β protein level in a neuronal culture.

Caffeine neuroprotective effects against beta-amyloid may correlate to glycogen synthase kinase-3β protein.</div>

Quercetin, a natural flavonoid, has been suggested as a stimulant of endogenous neural stem cell proliferation; but, its underlying mechanism is unclear. Considering that Nrf2 and proteasome pathways have important role in cell proliferation, the objective of this study was to evaluate the effects of different concentrations of quercetin on Nrf2 protein levels and proteasomal activity in neural stem/progenitor cells (NS/PCs) in relation to NS/PCs viability and proliferation.

NS/PCs of rat fetal ganglionic eminence were cultured and exposed to different concentrations of quercetin (1, 5 and 15μM) or DMSO for 7 days. The size and number of neurospheres and percentage of BrdU positive cells were measured as indexes of cell proliferation. MTT assay was used for evaluating the cell viability. Proteasomal activity and Nrf2 protein levels were determined using proteasomal activity kit and western immunoblotting, respectively.

Quercetin increased the percentage of BrdU positive cells, size and number of neurospheres and viability of NS/PCs and increased Nrf2 protein levels and 20S proteasome activity in comparison to DMSO. The effects of quercetin on NS/PCs proliferation, Nrf2 levels and proteasome activity were concentration-dependent.

The results of this study indicated that quercetin increased Nrf2 levels and proteasome activity in parallel to enhanced NS/PCs proliferation in a concentration-dependent manner. These findings suggest that quercetin may exert its stimulatory effect on NS/PCs proliferation through the enhancement of Nrf2-proteasome pathway. Quercetin as activators of Nrf2 and proteasome can be suggested as a potential treatment for neurodegenerative conditions to promote endogenous cell proliferation.</div>

Parkinson’s disease is a progressive neurodegenerative disorder characterized by progressive death of midbrain dopaminergic neurons. Neurosteroid dehydroepiandrosteone (DHEA) is synthesized de novo in brain glial cells and its concentration is particularly high in the brain, which dramatically decreases by aging. DHEA has neuroprotective activity against different types of neural injuries. In this study, we investigated the effects of DHEA on 6-hydroxydopamine (6-OHDA)-induced toxicity in rat pheochromocytoma (PC12) cells as an in vitro model of Parkinson’s disease.

Cell damage was induced by 150μM 6-OHDA and the cell survival rate was examined by MTT assay. The level of intracellular reactive oxygen species (ROS) was determined with a 2,7-dichlorofluorescein diacetate probe. Immunoblotting was also employed to determine the level of biochemical markers of neural apoptosis in PC12 cells.

The data demonstrated toxic effect of 6-OHDA by reducing cell viability in a dose-dependent manner. Furthermore, activated caspase-3 and Bax/Bcl2 ratio were significantly increased in 6-OHDA-treated cells. Incubation of cells with DHEA (400 and 600μg/ml) decreased cell damage.

Our results suggest that DHEA has protective effects against 6-OHDA-induced neural damage. The mechanisms of these effects may be due to the attenuation of neural apoptosis and suggest therapeutic potential of this neurosteroid in the treatment of Parkinson’s disease.</div>

Brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNFα) are two critical factors in multiple sclerosis (MS). The aim of the present study is comparing the crosstalk between BDNF and TNFα in the brain versus serum and their effects on recovery of C57BL/6 mice demyelination in cuprizone model.

Fifteen C57BL/6 mice 6-week-old in three different groups were used: control (standard rodent chow), cuprizone-exposed1 (CPZ1; 0.2% cuprizone feeding for 5 weeks) and cuprizone-exposed2 (CPZ2; 0.2% cuprizone feeding for 5 weeks followed by 2 weeks of cuprizone withdrawal). To prove MS induction and cognitive behavioral impairment, Y-maze test and histological studies with luxol fast blue staining were done. The levels of BDNF and TNFα in the brain and serum were measured by ELIZA kits.

In the present study, Y-maze test demonstrated that MS significantly impaired the cognitive behavior in both CPZ groups compared to control group. Demyelination in corpus callosum (CC) significantly was higher in the two CPZ groups relative to control group. The brain levels of BDNF significantly decreased while the brain levels of TNFα significantly increased in both CPZ groups compared to control group. Serum levels of BDNF and TNFα significantly increased in CPZ1 group compared to control group.

According to the present results, cuprizone-induced MS caused to an extensive demyelination in CC, which led to impaired cognitive behavior. Moreover, brain and serum levels of BDNF and TNFα as well as their crosstalk were affected by cuprizone exposure.</div>

Diabetes mellitus is a major chronic metabolic disorder that induces memory and learning impairment. Herein, we investigated the protective effects of cerium oxide nanoparticles (CeO2) against streptozotocin (STZ)-induced memory impairment and antioxidant capacity in the diabetic rats.

Adult male Wistar rats were assigned into the control, STZ, CeO2 and STZ plus CeO2 groups. Diabetes was induced using STZ and next CeNPs (60mg/kg) was administered for 14 constitutive days. The day after the last administration, spatial memory was assessed using the Morris water maze (MWM). Ultimately, the level of total antioxidant capacity (TAC) was investigated.

Our results showed that STZ significantly decreased the spatial memory and CeO2 could compensate for these changes. Furthermore, TAC increased following administration of CeO2 in the diabetic rats.

The results of this study suggest that CeO2 seems to be able to improve STZ-induced neurotoxicity in the rats.</div>

Effects of chronic scheduled dietary on plasma ghrelin and food intake in adult male rats were assessed.

Forty male Wistar rats (180-200g) were distributed into four groups (n=10), freely fed rats (control) and three scheduled-fed groups with different caloric intakes: high fat, standard and restricted diet. Then, plasma ghrelin and food intake were measured on days 0, 7 and 14.

Plasma ghrelin was significantly different among all groups, the scheduled-standard rats having the lowest ghrelin on day 7 and the restricted rats having the highest ghrelin on day 14. Noteworthy, fasted ghrelin in controls was as much as that of schedule groups exception restricted diet at the end of experiment. Controls consumed stable food over the time, while schedule groups showed time and caloric-dependency of food intake. Schedule-standard and restricted groups on feeding time consumed high level of food. Schedule-high fat group displayed a time dependent reduction in food intake. A positive correlation was found between plasma ghrelin and food intake in fasting status for freely fed rats and anticipating status for standard and restricted-schedule groups.

A component of ghrelin secretion can be entrained or learned for time feeding as well as long last-fasting and more is affected by quantitative and qualitative of caloric intake. Elevated ghrelin levels in restricted model are subjective both by low energy levels and learning. Also, caloric intake amount can be controlled by learning; we observed a reduction in meal size in scheduled–high fat diet.</div>

In this study, we investigated the effect of basil rosmarinic acid-rich extract on mice lipid metabolism, low-density lipoprotein oxidation and antiradical property.

The rosmarinic acid rich-extract was used to treat male mice. Mice were divided into four groups of seven mice and treatment was performed daily and orally for 9 weeks. The antihyperlipidemic effect was evidenced by the measurement of plasma and liver lipid profiles. Thiobarbituric acid reactive substances assay was used to measure the antioxidant capacity of the phenolic extract using mice plasma rich in low density lipoprotein (LDL). The antioxidant activity of the extract was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity and the measurement of oxidative β-carotene bleaching.

The extract exerts a significant decrease in plasma total cholesterol, triglycerides and LDL-cholesterol. Similar results were observed in liver total cholesterol and triglycerides. The phenolic extract prevents lipoprotein oxidation by 93% at a dose of 25μg/ml. We also note that the extract scavenges DPPH radical in a dose-dependent manner with an IC50= 12.45±0.18 μg/ml. Besides, the extract inhibits the oxidation process of β-carotene, the IC50 was 12.16±0.19 μg/ml. HPLC analysis shows that the extract contains caftaric acid (2.9%), caffeic acid (4.3%), chicoric acid (5.5%) and rosmarinic acid (87.3%) which is the major compound.

The results obtained suggest that the extract may be an important source of natural compounds that can be exploited as a substrate to develop new treatment of hyperlipidemia and atherosclerosis.</div>

Comorbidity of anxiety has been reported to aggravate the control of asthma symptoms. Considering the important role of oxidative stress in the pathophysiology of asthma and anxiety, the present study evaluated whether hydrogen sulfide (H2S) as an antioxidant agent, has anxiolytic effects in ovalbumin (OVA)-induced chronic asthma.

BALB/c mice were randomly divided into 4 groups (n=8): control, asthma, NaHS (sodium hydrosulfide, a donor of H2S) and ascorbic acid (as a positive control). All animals except in the control group were sensitized and challenged with ovalbumin. Mice in the NaHS group, intraperitoneally received 14μmol/kg NaHS 30min before each challenge. In the ascorbic acid group, 130mg/kg ascorbic acid was given by gavage 30min before each challenge. On the day of the last challenge, animal body weight and anxiety-related behaviors were examined.

Asthma caused significant decreases in the percentages of open arm entries and spending time in open arms in the elevated plus maze as well as the spending time in the light side in the light-dark transition. Also, induction of asthma resulted in a significant decrease of the animal body weight. Administration of NaHS as well as ascorbic acid, attenuated anxiety-related behaviors and improved the body weight in asthmatic mice.

The current study suggested that NaHS improves anxiety-related behaviors in OVA-induced asthma same as ascorbic acid, a strong antioxidant. Therefore, NaHS appears to be effective for managing the comorbidity of anxiety with asthma.</div>

Antioxidant and anti-inflammatory features of Centella asiatica (Centella) hydroalcoholic extract is documented in various diseases. This study aimed to investigate the effect of Centella hydroalcoholic extract on gentamicin (GM) induced nephrotoxicity.

In this study, 28 male Wistar rats were studied in 4 groups namely: control, sham, GM+normal saline (NS) and GM+Centella extract. In order to nephrotoxicity induction, gentamicin (100mg/kg) was injected as ip for seven days and then Centella (100 mg/kg/ip) administered for 7 consecutive days. Finally, the blood samples were collected from heart in order to measure the plasma creatinine (Cr) and urea nitrogen levels. Oxidative stress indices were also measured through assessing the malondialdehyde (MDA) and ferric reduction antioxidant power (FRAP) levels in right kidney. Moreover, histological damages were assessed through studying hematoxylin-eosin stained left kidney sections.

There was a significant increase in Cr, urea nitrogen and MDA levels, as well as renal tissue damages, while FRAP level reduced in the group received GM+NS compared to the sham one. Treatment with Centella resulted in a significant decrease in plasma Cr, urea nitrogen, MDA and tissue damages in the GM+Centella extract group compared to the GM+NS group. Moreover, FRAP level increased significantly in the GM+Centella group compared to the GM+NS group.

Treatment with Centella extract is effective for ameliorating the kidney damages in gentamicin-induced nephrotoxicity in rats.</div>

Nitric oxide (NO) is an important regulator involved in functional adaptation in all tissues to exercise, as shown in recent studies. The aim of this short-term study was to evaluate the hypothesis that the important factor of higher performance of trained females during exhaustive exercise can be the interaction between physiological effect of nitric oxide and oxidant/antioxidant response.

Males and females of trained mice were divided into three groups: basal, fasting and prolonged exercise. Parameters of oxidant/antioxidant state, including nitric oxide and glutathione were measured in blood, muscle, liver, heart, kidney, brain, small intestine, adipose tissue and thoracic aorta. Females in this animal model had better performance than males during exhaustive exercise.

Females showed greater basal levels of nitric oxide, total antioxidant status and glutathione peroxidase in most tissues evaluated. Compared to fasting levels, the net effects of prolonged exercise included lipoperoxidation in liver, brain and kidney, and nitrosative stress in liver, muscle and heart only in males. The decrement of glutathione without significant changes in its grade of oxidation was observed in liver, intestine and adipose tissue only in females, confirmed possible redistribution of reduced glutathione during prolonged exercise.

It is possible that the gender difference that existed in the performance of the animals during exhaustive exercise was determined by NO modulation of the oxidant/antioxidant response in tissues, and particularly of the redistribution of glutathione from the liver to other tissues. NO- induced vasodilatation can be beneficial for ischemic tissues during prolonged or exhaustive exercise.</div>