A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues. METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 µL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions. CONCLUSION: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.

A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.), also called Turkish oregano, is a perennial and herbaceous plant species grown for centuries for medicinal, cosmetic and culinary purposes. This is the first study to investigate the putative neuroprotective and pro-cognitive activities of O. onites essential oil (OOEO) against scopolamine-induced amnesia of AD-type in Wistar albino rats. The results of behavioral tests revealed that OOEO administration was able to significantly alleviate learning and memory impairments induced by scopolamine in vivo. The observed effects could be attributed to inhibition of acetylcholinesterase activity, attenuation of oxidative stress and prevention of neuronal apoptosis in the hippocampus and frontal cortex of AD rats. Modulation of pro-inflammatory enzymes, including cyclooxygenase-2, inducible nitric oxide synthase and myeloperoxidase, might further contribute to the neuroprotective properties of OEOO, as predicted by our in silico models. These findings offer novel insights into the therapeutic potential of OEOO in patients with AD.

Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats.

BACKGROUND: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. METHODS AND RESULTS: Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-ß), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-ß, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group. CONCLUSION: It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.

Evaluation of the Effect of Prazosin Treatment on α-2c Adrenoceptor and Apoptosis Protein Levels in the Predator Scent-Induced Rat Model of Post-Traumatic Stress Disorder.

The predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks α-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and α-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on α-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and α-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions.

Protective effects of spironolactone against hepatic ischemia/reperfusion injury in rats.

OBJECTIVES: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. MATERIAL AND METHODS: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1ß) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+-ATPase enzyme activities were analyzed to study tissue injury under light microscope. RESULTS: While IR increased AST, ALT, TNF-α, and IL-1ß levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. CONCLUSION: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

Protective effects of St. John's wort in the hepatic ischemia/reperfusion injury in rats.

OBJECTIVES: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. MATERIAL AND METHODS: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. RESULTS: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1ß levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. CONCLUSION: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Protective effect of silk fibroin in burn injury in rat model.

Activation of pro-inflamatuar pathways play major role in formation of major complications as a result of burns. This study was planned to investigate the protective effect of Silk Fibroin in lung injury caused by burn in the experimental rat model. After rinsing the skin of rats under ether anesthesia, the exposed back region, covers 30% of the total body, was kept in the 90°C water bath for 10s. The control rats were kept in the 25°C water bath for 10s. Immediately after burning process, silk fibroin was administered orally at a dose of 600mg/kg. After 24h following burning from all groups the levels of TNF-α, IL-1ß in blood samples and the MDA, GSH and the activity of MPO were determined from taken lung tissues. Moreover, the expression of Bcl-2/Bax, Caspase-3 and Caspase-9 were determined. Significant increase in TNF-α, IL-1ß, Casp-3 and Casp-9 levels were observed in the Silk Fibroin-treated burn group (p<0.05) whereas for ratio of Bcl-2/Bax, a significant reduction was observed compared to control group (p<0.05). Increased levels of TNF-α, IL-1ß, Caspase-3 and Caspase-9 in Silk Fibroin-treated burn groups were found to be reversed. Silk fibroin can be an effective biomaterial in diminishing burn injury in tissue and apoptosis.

Protective effect of betaine against burn-induced pulmonary injury in rats.

BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.