Carvone suppresses oxidative stress and inflammation in the liver of immobilised rats.

OBJECTIVE: The investigation of the effect of carvone (a natural monoterpene) on liver damage caused by chronic immobilisation. METHODS: Male Wistar rats were divided into four groups: control, carvone, stress, and stress-carvone. To induce stress, rats were placed in a restrainer (6 h/21 day) and carvone was treated by gavage at a dose of 20 mg/kg. RESULTS: Alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase activities were significantly increased in sera of immobilised rats. Chronic immobilisation also increased malondialdehyde levels and decreased reduced glutathione content, as well as increased TNF-α, IL-1ß, IL-6, and NF-κB mRNA expression and also led to the infiltration of inflammatory cells in the liver parenchyma. Carvone's 21-day treatment prevented all of these changes in immobilised rats. CONCLUSION: It is concluded that carvone has effectively prevented chronic immobilisation-induced liver injury, most probably through its antioxidant and anti-inflammatory capabilities.

Neuroprotective effect of alpha-pinene is mediated by suppression of the TNF-α/NF-κB pathway in Alzheimer's disease rat model.

Monoterpene alpha-pinene possesses antioxidant, cardioprotective, and neuroprotective properties. We evaluated the effect of alpha-pinene on oxidative/nitrosative stress, neuroinflammation, and molecular and behavioral changes induced by beta-amyloid (Aß)1-42 in rats and investigated the possible mechanisms of these outcomes. Male Wistar rats received alpha-pinene (50 mg/kg intraperitoneally) for 14 consecutive days after intrahippocampal injection of Aß1-42 . Alpha-pinene decreased malondialdehyde and nitric oxide levels, increased glutathione content, and enhanced catalase activity in Aß-injected rats. Also, messenger RNA expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6, nuclear factor κB, and N-methyl- d-aspartate receptor subunits 2A and 2B reduced in the hippocampus of these animals. Besides this, alpha-pinene repressed the Aß1-42 -induced reduction of nicotinic acetylcholine receptor α7 subunit and brain-derived neurotrophic factor expression. Treatment with alpha-pinene caused Aß-receiving rats to spend more time in the target quadrant in the Morris water maze test and led to an increase in percentages of open arm entrance and time spent in the open arm in the elevated plus-maze test. We concluded that alpha-pinene strengthens the antioxidant system and prevents neuroinflammation in the hippocampus of rats receiving Aß. It improves spatial learning and memory and reduces anxiety-like behavior in these animals. Consequently, alpha-pinene alleviates Aß-induced oxidative/nitrosative stress, neuroinflammation, and behavioral deficits. It is probably a suitable candidate for the treatment of neurodegenerative diseases.

Mediatory role of the central NPY, melanocortine and corticotrophin systems on phoenixin-14 induced hyperphagia in neonatal chicken.

Animal research indicates the neuropeptide Y (NPY), corticotrophin and melanocortin systems have a mediatory role in reward, however, how these substances interact with phenytoin-14 (PNX-14) induced food intake in birds remains to be identified. Accordingly, in this research eight tests were carried out to investigate the potential interactions of the NPY, melanocortin, as well as corticotrophin systems with PNX-14 on food consumption in neonatal chickens. In the first experiment, chickens were intracerebroventricular (ICV) injected with phosphate-buffered saline (PBS) and PNX-14 (0.8, 0.16, and 3.2 nmol). In second experiment, PBS, the antagonist of CRF1/CRF2 receptors (astressin-B, 30 µg) and PNX-14 + astressin-B were injected. In the rest of the experiments chicken received astressin2-B (CRF2 receptor antagonist; 30 µg), SHU9119 (MCR3/MCR4 receptor antagonist, 0.5nomol), MCL0020 (MCR4 receptor agonist, 0.5 nmol), B5063 (NPY1 receptor antagonist, 1.25 µg), SF22 (NPY2 receptor antagonist, 1.25 µg) and SML0891 (NPY5 receptor antagonist, 1.25 µg) rather than astressin-B. Then, cumulative intake of food was recorded for 2 h. Based on the findings, PNX-14 (0.16 and 3.2 nmol) led to increment in food consumption compared with the control (P < 0.05). Co-administration of the PNX-14 and astressin-B promoted PNX-14-induced hyperphagia (P < 0.05). Co-injection of the PNX-14 + astressin2-B potentiated hyperphagia PNX-14 (P < 0.05). Co-injection of PNX-14 + B5063 inhibited the effects of the PNX-14 (P < 0.05). The co-administration of the PNX-14 and SML0891 potentiated hypophagic effects of the PNX-14 (P < 0.05). The results showed that PNX-14-induced hyperphagia mediates via NPY1, NPY5, and CRF1/CRF2 receptors in neonatal chickens.

Viola tricolor Hydroalcoholic Extract Improves Behavioral Deficiencies in Rats Exposed to Chronic Immobilization Stress

Abstract This study aims to investigate the effect of Viola tricolor extract on hippocampal neuronal death, interleukin (IL) -6 and IL-10 expression, spatial memory, anxiety, and depression in rats exposed to chronic immobilization stress. Rats were divided into groups Control, Viola300, Viola600, Stress, Stress-Viola300, and Stress-Viola600. Animals were placed in a restrainer (6 h / 21 days) to stress exposure. V. tricolor hydro-alcoholic extract was also administrated at doses of 300 and 600 mg/kg by gavage. The extract caused immobilized animals to spend more time in the target quadrant in the Morris water maze test. It also increased the percentage of entries into the open arm and the percentage of time spent in the open arm of the elevated plus-maze in immobilized rats. Treatment with the V. tricolor extract significantly reduced the immobility time of stressed rats in the forced swimming test. Furthermore, it significantly reduced neuronal death and expression of IL-6 in the hippocampus of immobilized animals but could not prevent the decrease of IL-10 expression. We concluded that V. tricolor protects rats from stress-induced behavioral damages, at least in part, by suppressing neuronal death and decreasing IL-6 expression.

Morin attenuates memory deficits in a rat model of Alzheimer's disease by ameliorating oxidative stress and neuroinflammation.

This study aimed to investigate the effect of flavonoid morin on oxidative/nitrosative stress, neuroinflammation, and histological, molecular, and behavioral changes caused by amyloid-beta (Aß)1-42 in male Wistar rats (Alzheimer's disease model). Rats received morin (20 mg/kg, oral gavage) for 14 consecutive days after intrahippocampal injection of Aß1-42. Morin decreased the levels of malondialdehyde and nitric oxide, increased glutathione content, and enhanced catalase activity in the hippocampus of animals receiving Aß1-42. It also reduced the expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6, nuclear factor-kappa B, and N-methyl-D-aspartate receptor subunits 2A and 2B and increased the expression of brain-derived neurotrophic factor and α7 nicotinic acetylcholine receptor in the hippocampus of Aß1-42-injected rats. Besides, morin modified neuronal loss and histological changes in the CA1 region of the hippocampus. Morin allowed Aß1-42-infused rats to swim more time in the target quadrant in the Morris water maze test. It is concluded that morin may be suitable for the prevention and treatment of Alzheimer's disease by strengthening the antioxidant system, inhibiting neuroinflammation, preventing neuronal death, and enhancing memory function.

Protective effect of alpha-linoleic acid on Aß-induced oxidative stress, neuroinflammation, and memory impairment by alteration of α7 nAChR and NMDAR gene expression in the hippocampus of rats.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects many older people around the world. Numerous studies are underway to evaluate the protective effects of natural products in AD. Alpha-linoleic acid (ALA) is an essential unsaturated fatty acid that exhibits neuroprotective outcomes in rat models of ischemic stroke and Parkinson's disease. This research aimed to investigate the effect of ALA on oxidative stress, neuroinflammation, neuronal death, and memory deficit induced by amyloid-beta (Aß) peptide. After intrahippocampal injection of Aß1-42, rats received ALA (150 µg/kg, subcutaneously) for 14 consecutive days. ALA decreased the levels of malondialdehyde and nitric oxide, enhanced glutathione content, and increased the activity of catalase in the hippocampus of the rat model of AD. It also reduced the expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6, nuclear factor-kappa B, and N-methyl-d-aspartate receptor subunits NR2A and NR2B mRNAs in the hippocampus, prevented the neuronal loss in the CA1 region, and enhanced the expression of α7 nicotinic acetylcholine receptor. In addition, ALA allowed Aß1-42-injected rats to spend less time and distance to reach the hidden platform in the Morris water maze test and to swim longer in the target quadrant. We concluded that ALA reduces the biochemical, molecular, histological, and behavioral changes caused by Aß1-42 and it may be an effective option for treating AD.

Sphingosin-1-phosphate Receptor 1: a Potential Target to Inhibit Neuroinflammation and Restore the Sphingosin-1-phosphate Metabolism.

BACKGROUND: Recent evidence suggests that an extreme shift may occur in sphingosine metabolism in neuroinflammatory contexts. Sphingosine 1-phosphate (S1P)-metabolizing enzymes (SMEs) regulate the level of S1P. We recently found that FTY720, a S1P analogue, and SEW2871, a selective S1P receptor 1 (S1P1) agonist, provide protection against neural damage and memory deficit in amyloid beta (Aß)-injected animals. This study aimed to evaluate the effects of these two analogues on the expression of SMEs as well as their anti-inflammatory roles. METHODS: Rats were treated with intracerebral lipopolysaccharide (LPS) or Aß. Memory impairment was assessed by Morris water maze and the effects of drugs on SMEs as well as inflammatory markers, TNF- α and COX-II, were determined by immunoblotting. RESULTS: Aß and LPS differentially altered the expression profile of SMEs. In Aß-injected animals, FTY720 and SEW2871 treatments exerted anti-inflammatory effects and restored the expression profile of SMEs, in parallel to our previous findings. In LPS animals however, in spite of anti-inflammatory effects of the two analogues, only FTY720 restored the levels of SMEs and prevented memory deficit. CONCLUSION: The observed ameliorating effects of FTY720 and SEW7821 can be partly attributed to the interruption of the vicious cycle of abnormal S1P metabolism and neuro-inflammation. The close imitation of the FTY720 effects by SW2871 in Aß-induced neuro-inflammation may highlight the attractive role of S1P1 as a potential target to restore S1P metabolism and inhibit inflammatory processes.

Prominence of central sphingosine-1-phosphate receptor-1 in attenuating aß-induced injury by fingolimod.

FTY720 (fingolimod), the sphingosine-1-phosphate (S1P) analogue, has been experimentally indicated to exert substantial ameliorating effects in animal models of Alzheimer's disease (AD). The present work aims to answer whether central S1P receptor 1 (S1P1) plays significant role in the impact of fingolimod in AD. To verify the prominence of central FTY720 phosphorylation, DMS (sphingosine kinase inhibitor) was infused intracerebrally in parallel with systemic FTY720 administration to prevent central formation of FTY720-P as the recognized active ligand for S1PRs. The corresponding S1P1 modulation was also investigated using the pharmacological blockage of central S1P1 by W123. Both DMS and W123 were efficiently capable of suppressing FTY720-ameliorating effects in AD animals, either on memory deficit or on COX-II and TNF-α expression. Our data conclude that experimental benefits of FTY720 in the context of AD depend on central S1P1 modulation, as well as on S1P kinase activity in the brain.