Thymol mitigates cadmium-induced behavioral and cognitive deficits by up-regulating hippocampal BDNF levels in rats.

Cadmium is a potent neurotoxin and induces adverse impact on brain function. Protective effects of monoterpenes on the CNS have been reported previously. The present study was designed to investigate the beneficial effect of thymol on cadmium-induced neurotoxicity. Rats were initially divided into 2 groups, vehicle control and thymol. Thymol (40mg/kg) was given orally for 14 days. Each group was subdivided into two groups (Vehicle control and Cadmium, Thymol and Thymol+Cadmium). Cadmium Chloride (5mg/kg) was given for last 3 days only to the groups assigned as Cadmium and Thymol+Cadmium. Behavioral parameters were assessed after 24h of last dose of cadmium. Brain sample were collected and BDNF was measured in hippocampus. The present study suggests that pre-administration of thymol provides a protective therapy against cadmium-induced intoxication by enhancing the brain BDNF levels and plasticity. Results further suggest that thymol not only ameliorates cadmium-induced learning and memory impairment but also reduced anxiety, motor incoordination and depression assessed by various behavioral tests. The study may provide a better apprehension of the neuroprotective role of thymol and highlighting its significance in the diet for human health particularly in cadmium intoxication.

Aberrant STAT1 methylation as a non-invasive biomarker in blood of HCV induced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancer in the world and a reason behind different oncogenes activation and tumor suppressor genes inactivation. Hyper-methylation of tumor suppressor genes including RASSF1a, GSTP1, p16, and APC cause gene silencing as well as tumor cell invasion. STAT 1 gene is a part of signaling cascade of JAK/STAT and any dysregulation in signaling has been implicated in tumor formation. OBJECTIVE: The current investigation focus on the methylation role of STAT1 gene as a non-invasive biomarker in the progression and diagnosis of hepatocellular carcinoma. METHODS: STAT1 gene methylation status in 46 HCV induced hepatocellular carcinoma patients and 40 non-HCC controls were examined by methylation specific PCR. STAT1 gene expression was examined by real time PCR and further validated by various bioinformatics tools. RESULTS: STAT1 methylation in HCV-induced HCC (67.4%) was significantly higher compared to the non-HCC controls (p< 0.01). However, mRNA expression of STAT1 gene in methylated groups was significantly lower compared to unmethylated groups (p< 0.05). Furthermore, insilco analysis of STAT1 validated our results and shown expression of STAT1 mRNA was lower in liver cancer with the median 24.3 (p= 0.085). CONCLUSION: After using peripheral blood samples we observed that STAT1 silencing caused by aberrant methylation could be used as potential non-invasive biomarker for the diagnosis of HCV induced hepatocellular carcinoma. We conclude that blood as a sample source could be used instead of biopsy for early detection of HCC.

Neuroprotective role of a monoterpene (thymol) on diazepam induced withdrawal symptoms in rats.

Benzodiazepine administration is known to be related to tolerance and a withdrawal syndrome on sudden cessation. Thymol possesses multiple biological properties especially in the pathogenesis of different brain disorders. However, to the best of our knowledge there is no study that relates the use of thymol to benzodiazepine induced withdrawal symptoms. Therefore the aim of the current study was to investigate the usefulness of thymol in the treatment of benzodiazepine withdrawal syndrome in rats. Animals were divided into four groups, thymol (40mg/kg/ml), diazepam (4 mg/kg), thymol + diazepam and vehicle control group. The treatment was given for 14 days and then suddenly ceased. After 24 h animals were tested in different behavioral paradigms such as physical signs for withdrawal, marble burying test, inverted screen test, elevated plus maze, passive avoidance test and open field activity. The results of the present study revealed that co-administration of thymol significantly reduced the withdrawal symptoms induced by diazepam. Our results further suggest that administration of thymol not only ameliorates rebound anxiety associated with diazepam withdrawal but also improves motor and memory impairment in rats.

Curcumin lessens unpredictable chronic mild stress-induced depression and memory deficits by modulating oxidative stress and cholinergic activity.

Unpredictable chronic mild stress (UCMS) model is the most established method to study neurobiological mechanisms of depression. This work was intended to explore the efficacy of curcumin to revert the UCMS-induced oxidative burden and associated depression as well as potential of curcumin as an acetyl cholinesterase (AchE) inhibitor. Animals were initially grouped into control and curcumin (200mg/kg, p.o) and further subdivided into unstressed and stressed groups. Depression and anxiety were evaluated by forced swim test (FST) and light/dark transition (LDT) while memory function was assessed by passive avoidance test (PAT). Effect of curcumin on oxidative stress following UCMS was determined by measuring peroxidation of lipid (LPO) and antioxidant enzyme activities. AchE activity was also determined. Findings showed that curcumin supplementation significantly attenuated the UCMS-induced depression and anxiety like symptoms, decreased the load of UCMS propagated oxidative stress by improving antioxidant enzymes activities. Curcumin also improved the memory function and exhibited inhibitory effect on AchE activity. In conclusion it can be suggested that supplementation of curcumin in daily life can help in combating the stress-induced depression and ever increasing load of oxidative stress. Study also highlights the anti-acetylcholinesterase potential of curcumin which may be responsible for improved memory function following UCMS.

A comparative study showing greater effects of curcumin compared to donepezil on memory function in rats.

Curcumin possesses wide spectrum of biological actions, on that account the current study was aimed to investigate the beneficial effectiveness of curcumin on memory and oxidative stress if any, over synthetic drug donepezil approved for the treatment of memory disorders. Eighteen Albino wistar (male) rats were divided into 3 groups namely vehicle control which received neutral oil orally and 0.9% saline intraperitoneally, curcumin which received curcumin orally dissolved in neutral oil at the dose of 100mg/ml/kg for seven days, donepezil which received donepezil intraperitoneally at the dose of 1mg/ml/kg for seven days. To assess memory and cognition Elevated Plus Maze and Morris Water Maze tests were performed. Rats were sacrificed after behavioral analysis and their brains were removed for biochemical assays including lipid peroxidation and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase. Acetylcholine esterase activity and acetylcholine levels were also determined. Our results showed that both curcumin and donepezil improved memory and inhibited acetylcholinesterase, however curcumin inhibited AchE with more potency than donepezil when compared to vehicle control rats. Moreover curcumin exhibited greater antioxidant potential to decrease the load of oxidative stress in brain cells than donepezil as compared to vehicle control rats. In conclusion present study proposed that increased antioxidant potential of curcumin may be responsible for its increased acetylcholine levels and associated enhanced memory performance.

Enriched environment palliates nicotine-induced addiction and associated neurobehavioral deficits in rats.

This study was designed to investigate the role of enriched environment in preventing and/or reducing the neurobehavioral deficits produced after nicotine administration in albino Wistar rats. Equal numbers of rat in two groups were either placed in social environment (control group) or social along with physically enriched environment for four weeks before the administration of nicotine. Exposure to different environmental conditions was followed by the intraperitoneal injection of nicotine at the dose of 0.6 mg/kg for seven consecutive days during which addictive behavior was monitored using conditioned placed preference paradigm. Behavioral responses to locomotor activity, anxiety and retention of short term memory were investigated in control and nicotine injected groups exposed to different environments. Results of this study showed that the rats pre-exposed to physical along with social enrichment exhibited a decrease in drug seeking behavior, hyper locomotion, anxiogenic effects along with improvement of working memory as compared to control and nicotine injected groups that were kept in social environment alone. This behavioral study suggests that the exposure to physical enrichment along with socialization in young age can later reduce the chances of compulsive dependence on nicotine and related neurobehavioral deficits.

Pretreatment with curcumin attenuates anxiety while strengthens memory performance after one short stress experience in male rats.

It is observed that memories are more strengthened in a stressful condition. Studies have also demonstrated an association between stressful events and the onset of depression and anxiety. Considering the nootropic, anxiolytic and antidepressant-like properties of curcumin in various experimental approaches, we appraised the beneficial effects of this herb on acute immobilization stress-induced behavioral and neurochemical alterations. Rats in test group were administrated with curcumin (200mg/kg/day), dissolved in neutral oil, for 1 week. Both control and curcumin-treated rats were divided into unstressed and stressed groups. Rats in the stressed group were subjected to immobilization stress for 2h. After stress, the animals were subjected to behavioral tests. Immobilization stress induced an anxiogenic behavior in rats subjected to elevated plus maze test (EPM). Locomotor activity was also significantly increased following the acute immobilization stress. Pre-administration of curcumin prevented the stress-induced behavioral deficits. Highest memory performance was observed in stressed rats that were pre-treated with curcumin in Morris water maze (MWM). Brain malondialdehyde (MDA) levels, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and acetylcholinesterase (AChE) activities were also estimated. Present study suggests a role of antioxidant enzymes in the attenuation of acute stress induced anxiety by curcumin. The findings therefore suggest that supplementation of curcumin may be beneficial in the treatment of acute stress induced anxiety and enhancement of memory function.

Altered brain serotonergic neurotransmission following caffeine withdrawal produces behavioral deficits in rats.

Caffeine administration has been shown to enhance performance and memory in rodents and humans while its withdrawal on the other hand produces neurobehavioral deficits which are thought to be mediated by alterations in monoamines neurotransmission. A role of decreased brain 5-HT (5-hydroxytryptamine, serotonin) levels has been implicated in impaired cognitive performance and depression. Memory functions of rats were assessed by Water Maze (WM) and immobility time by Forced Swim Test (FST). The results of this study showed that repeated caffeine administration for 6 days at 30 mg/kg dose significantly increases brain 5-HT (p<0.05) and 5-HIAA (p<0.05) levels and its withdrawal significantly (p<0.05) decreased brain 5-HT levels. A significant decrease in latency time was exhibited by rats in the WM repeatedly injected with caffeine. Withdrawal of caffeine however produced memory deficits and significantly increases the immobility time of rats in FST. The results of this study are linked with caffeine induced alterations in serotonergic neurotransmission and its role in memory and depression.