Gefitinib loaded nanostructured lipid carriers: characterization, evaluation and anti-human colon cancer activity in vitro.

NLC containing Gefitinib (NANOGEF) was prepared using stearic acid, sesame oil and surfactants (sodium lauryl sulfate and tween 80). NANOGEFs were evaluated for particle size, polydispersity index (PdI), zeta potential, entrapment efficiency (EE), stability, release studies and cytotoxicity studies (MTT assay). The optimized NANOGEF exhibited particle size of 74.06 ± 9.73 d.nm, PdI of 0.339 ± 0.029 and EE of 99.76 ± 0.015%. The TEM study revealed spherical shape of NANOGEF formulations. The slow and sustained release behavior was exhibited by all NANOGEFs. The effects of surfactants were observed not only on particle size but also on zeta potential, entrapment efficiency, stability and release studies. The MTT assay revealed 4.5 times increase in cytotoxicity for optimized NANOGEF (IC50 = 4.642 µM) when compared with Gefitinib alone (IC50 = 20.88 µM in HCT-116 cells). Thus NANOGEF may be considered as a potential drug delivery system for the cure of colon cancer.

Development of Formulation Methods and Physical Characterization of Injectable Sodium Selenite Nanoparticles for the Delivery of Sorafenib tosylate.

BACKGROUND: Sorafenib is the first oral therapeutic agent to show the activity against human hepatocellular carcinoma. Sorafenib leads to severe toxicity due to the multiple-dose regimen. Reducing the overall dose of sorafenib through injectable dosage form to release sustainably is of therapeutically more important to combat drug-induced toxicity. OBJECTIVE: The purpose of this study was to formulate and evaluate the physical parameters of sorafenib- loaded Sodium Selenite Nanoparticles (SSSNP). METHODS: Two different methods: chemical crosslinking and solvent evaporation were applied for the formulation of nanoparticles using various crosslinkers such as formaldehyde, magnesium sulfate, tripolyphosphate, dextran sulfate, and aluminum hydroxide. Physical characterization was performed with zeta potential analysis, polydispersity index, particle size and scanning electron microscopic studies for morphological analysis for all the formulated nanoparticles developed using the chemical crosslinking technique based ionic interaction. RESULTS: Tripolyphosphate was selected as an ideal crosslinker and used for nanoparticle formulation with the solvent evaporation technique. Based on the physical characterization, SSSNP was formulated successfully with the solvent evaporation technique using tripolyphosphate as a cross-linker. The zeta potential of SSSNP was -37.5 mV, PDI was approximately 0.3 to 0.4, and the observed size (diameter) was in the range of 208 nm to 0.2 µm. Furthermore, the particles were smooth in morphology and appeared as crystals. CONCLUSION: The novel injectable sorafenib loaded sodium selenite nanoparticle dosage form will serve better than conventional oral dosage form to elicit a safe therapeutic effect.

Hepatoprotective Potential of Sargassum muticum against STZ-Induced Diabetic Liver Damage in Wistar Rats by Inhibiting Cytokines and the Apoptosis Pathway.

Liver inflammation and necrosis are the foremost problems interlinked with diabetes mellitus (DM). The methanolic extract of Sargassum muticum (MESM) plays a hepatoprotective role in streptozotocin- (STZ-) induced hepatic injury. In this study, STZ exposure induced diabetes that augmented hepatic damage, which was reflected in serum enzyme markers, the cytokine network, and caspase-3 and caspase-9 levels in Group 2. Exposure to the MESM tremendously modulated the levels of hepatic enzyme markers ALP, ACP, ALT, and AST in Groups 3 and 4. The cytokine network was well regulated by suppressing the release of cytokines, and the levels of caspase-3 and caspase-9 were also reduced in Groups 3 and 4. The present study suggests that MESM treatment at 200 and 500 mg protected the liver and also minimizes the glucose level. Thus, the MESM plays a key role in rejuvenating the liver and can modulate diabetes's pathogenic effect by reducing the glucose level.

Thymoquinone and fluoxetine alleviate depression via attenuating oxidative damage and inflammatory markers in type-2 diabetic rats.

The study was designed to find out the effect of thymoquinone (TQ) alone and combination of TQ + fluoxetine in depression of type-2 diabetic rats. Glucose level was significantly decreased in TQ alone treated group, whereas no significant change was recorded when TQ was combined with fluoxetine. Administration of TQ alone and combination of TQ and fluoxetine significantly decreased immobility time, increased latency to immobility and increased locomotor activity. Treatment with TQ alone significantly decreased level of TBARS, increased GSH and restored the activities of antioxidant enzymes (GPx, GR & CAT). However, TQ and fluoxetine combination reduced TBARS level, increased GSH content but no change in the antioxidant enzymes activities. Inflammatory markers (IL-1ß, IL-6 & TNF-α) levels were significantly reduced after the administration of TQ alone and TQ + fluoxetine. The study suggests that combination of TQ and fluoxetine can be used to control depression in type-2 diabetes mellitus.

Therapeutic potential of Vanillylacetone against CCl4 induced hepatotoxicity by suppressing the serum marker, oxidative stress, inflammatory cytokines and apoptosis in Swiss albino mice.

The aim of this research was to investigate the therapeutic potential of Vanillylacetone against carbon tetrachloride (CCl4) induced hepatotoxicity in mice through understanding the serum marker, oxidative stress mechanism and cytokine networks. Carbon tetrachloride is highly hepatotoxic used as research based on animal model. The mice were classified into five groups and each had eight mice. Group-I was controlled and the vehicle was given orally. Group-II was toxic and carbon tetrachloride (1.5 ml/kg) twice a week for 15 days was administered by intra-peritoneal injections. Group- III and IV were pre-treated with Vanillylacetone 50 & 100 mg kg-1 body weight given every day p.o. while, Group-V received only Vanillylacetone (100 mg kg-1 body weight) for 15 days orally. The finding indicates that the administration of CCl4 causes significant elevation of enzyme markers, oxidative stress, inflammatory cytokine and apoptotic markers in Group-II as compared to Group-I. The administration of Vanillylacetone (50 and100 mg kg-1) significantly suppresses the elevated serum enzymes, oxidative stress (TBARS), an inflammatory cytokine (IL2 and TNFα) and apoptotic markers (Caspase-3 and 9) in Group-III and IV as compared to Group-II. It was also noticed that the higher dose of Vanillylacetone (100 mg) is more effective than lower dose of Vanillylacetone (50 mg). There were no significant changes observed with higher dose of Vanillylacetone (100 mg kg-1) in Group-V as compared to Group-I. Histopathological analysis also supported the above findings. Overall, this results shows that Vanillylacetone has a good antioxidant and therapeutic properties which can help in preventing the chemically (CCl4) induced hepatotoxicity.

Thymoquinone Ameliorates Doxorubicin-Induced Cardiotoxicity in Swiss Albino Mice by Modulating Oxidative Damage and Cellular Inflammation.

Thymoquinone is the active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions. In present study, we have analyzed the effects of thymoquinone on doxorubicin (DOX) induced cardiotoxicity in mice. In this experiment, thirty mice (25-35 gm) were divided into five groups (Groups A, B, C, D, and E) each containing six animals. Normal saline was given to a control group (Group A) for 14 days. Cardiotoxicity was induced by DOX (15 mg/kg, i.p.) in Group B, once on the 13th day of the study, and Groups C and D also received DOX (15 mg/kg, i.p.) and were then treated with thymoquinone (10 and 20 mg/kg, b/w, p.o.), respectively, for 14 days. Group E was given only thymoquione (20 mg/kg b/w, p.o.). A blood serum marker (AST, ALT, CK-MB, and LDH) and oxidative stress marker (LPO, GSH, CAT, SOD, GPx, GR, and GST) were evaluated. Results revealed that serum enzyme marker like aspartate aminotransferase (AST), creatinine kinase-MB (CKMB), and lactate dehydrogenase (LDH) were significantly elevated in Group B as compare to Group A. Similarly, the oxidative stress marker lipid peroxidation (LPO) was also elevated in Group B while the antioxidant enzyme catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase (CAT, SOD, GPx, GR, and GST) were also decreased in Group B. The treatment with thymoquinone 10 and 20 mg/kg resulted in a significant decrease in the serum marker and increase in the antioxidant enzymes. In this study, we have found that thymoquinone prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels towards normalcy in Groups C and D. The effect of doxorubicin increases the inflammatory cytokine (IL2) in Group B as compared to Group A, and it overcomes by the thymoquinone in Groups C and D. Thus, thymoquinone may have utility as a potential drug for cardiomyopathy.

Nephroprotective Effect of Zingerone against CCl4-Induced Renal Toxicity in Swiss Albino Mice: Molecular Mechanism.

The protective effects of Zingerone against CCl4 induced nephrotoxicity in Swiss albino mice via modulation of metabolizing enzyme, oxidative stress, inflammatory cytokines, and apoptosis. The biochemical estimation indicated that the BUN and creatinine were significantly increased in group 2 (CCl4) compared to group 1 (normal) which was significantly reduced after treatment with Zingerone in group 3 when compared with group 2. The CCl4 treatment has significantly increased TBARS levels and reduced the antioxidant enzyme such as GSH, GPx, GR, GST, CAT, and SOD in group 2 compared to group 1, while the Zingerone treatment showed significant reduction in TBARS levels and increased the antioxidant enzymes in group 3 (CCl4 + Zingerone) as compared to group 2. Similarly, it was observed that CCl4 significantly increased the cytokines such as IL-1ß, IL-2, and TNFα levels in group 2 as compared to group 1. The treatment with Zingerone significantly attenuated the levels of IL-1ß, IL-2, and TNFα in group 3 compared to group 2. Caspase 3 and caspase 9 were also significantly increased in CCl4-treated group 2, whereas Zingerone treatment significantly reduced the elevated levels of caspases 3 and 9 in group 3 compared to group 2.

Catha Edulis Active Principle, Cathinone, Suppresses Motor Coordination, Accelerates Anxiety and Alters the Levels of Dopamine and its Metabolites in the Limbic Areas of Male Swiss Albino Mice.

Cathinone, the active principle of khat (Catha edulis), stimulates, excites and produces euphoric feelings in khat users. Locomotor and rearing activities, either individual or in groups, of male Swiss albino mice were decreased significantly compared to the control. Motor coordination tests (rotarod, rope climb and grip tests) have shown decreased motor performance in the mice treated with cathinone compared to the control. The elevated plus maze test has shown significant anxiety in the mice compared to the control. Contents of dopamine and its metabolite, homovanillic acid, were increased in the limbic areas compared to the control group. In contrast, contents of 3,4-dihydroxyphenyl acetic acid were depleted significantly and dose dependently compared to the control group in the limbic areas of mice. In conclusion, natural cathinone has depleted motor coordination, accelerated anxiety in mice and altered the contents of dopamine and its metabolites.

REPEATED EXPOSURE OF SODIUM TELLURITE ON THE RAT LIVER AND ON THE POTENTIAL MECHANISMS OF THE METALLOID-INDUCED HEPATOTOXICITY.

Tellurium (Te) is a semiconductor and is frequently doped with copper, tin, gold or silver. It is also used to color glass and ceramics and is one of the primary ingredients in blasting caps. Te is little known about its biological activity but it is well known for toxic to human and animals. It has inhibited the lipids profiles and oxidative stress in the brain of the mice. Sodium tellurite 4.15, 8.3 and 16.6 mg/kg (1/20, 1/10 and 1/5 of LD50, respectively) was given to male Wistar rats orally in saline for a period of 15 days. On day 16, the blood was collected and the livers were dissected out for biochemical assays. The hepatotoxicity biomarkers [biliru- bin, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP)] were ele- vated significantly and dose dependently in the serum of Te treated groups as compared to control group. The content of thiobarbituric acid reactive substances in Te treated groups was increased significantly and dose- dependently as compared to control group. Conversely, the content of glutathione and activities of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase) were decreased significantly in Te treated groups as compared to control group. No data of effect of inorganic Te compounds on the liver toxicity of rats are available. The aim of the present study was to evalu- ate the hepatotoxicity of inorganic Te compounds. In conclusion, Te accelerated hepatotoxicity and oxidative stress in liver tissue of rats.

REPEATED EXPOSURE OF SODIUM TELLURITE ON THE RAT LIVER AND ON THE POTENTIAL MECHANISMS OF THE METALLOID-INDUCED HEPATOTOXICITY.

Tellurium (Te) is a semiconductor and is frequently doped with copper, tin, gold or silver. It is also used to color glass and ceramics and is one of the primary ingredients in blasting caps. Little is known about Te biological activity but it is well known for toxicity to human and animals. It has inhibited the lipids profiles and oxidative stress in the brain of mice. Sodium tellurite 4.15, 8.3 and 16.6 mg/kg (1/20, 1/10 and 1/5 of LD50, respectively) was given to male Wistar rats orally in saline for a period of 15 days. On day 16, the blood was collected and the livers were dissected out for biochemical assays. The hepatotoxicity biomarkers [bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP)] were elevated significantly and dose dependently in the serum of Te treated groups as compared to control group. The content of thiobarbituric reactive substances in Te treated groups was increased significantly and dose-dependently as compared to control group. Conversely, the content of glutathione and activities of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase and catalase) were decreased significantly in Te treated groups as compared to control group. No data of inorganic Te compounds on the liver toxicity of rats are available. The aim of the present study was to evaluate the hepatotoxicity of inorganic Te compound. In conclusion, Te accelerated hepatotoxicity and oxidative stress in liver tissue of rats.

In Vitro Antibacterial Spectrum of Sodium Selenite against Selected Human Pathogenic Bacterial Strains.

The objective of this investigation was to predict the antibacterial properties of sodium selenite against selected human pathogens. A group of six human bacterial pathogens including Staphylococcus aureus, Streptococcus pyogenes, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella planticola were utilized for screening. The spectrum of activity was qualified based on zone of inhibition. Our study demonstrated that sodium selenite exhibits a strong spectrum of activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Klebsiella planticola. The spectrum of activity was compared with standard ciprofloxacin disc (5 µg/disc) and observed to have satisfactory effect.

Effect of hesperidin on neurobehavioral, neuroinflammation, oxidative stress and lipid alteration in intracerebroventricular streptozotocin induced cognitive impairment in mice.

Recent attention is given to the influence of dietary supplementation on health and mental well-being. Oxidative stress is associated with many diseases including neurodegenerative disorders. Dietary flavonoids exert chemopreventive and neuroprotective effects and comprise the most common group of plant polyphenols that provide much of the flavour and colour of the vegetables and fruits. Hesperidin is a flavanone glycoside found abundantly in citrus fruits, has been reported to have antioxidant, hypolipidaemic, analgesic and anti-hypertensive activity. Pretreatment of hesperidin (100 and 200mg/kg body weight orally once daily for 15 days) to Swiss male albino mice has prevented the cognitive impairment. The cognitive impairment was developed by giving single intracerebroventricular-streptozotocin (ICV-STZ) injection (2.57 mg/kg body weight each side) bilaterally. Hesperidin pretreatment improved memory consolidation process as tested by Morris water maze possibly through modulation of acetylcholine esterase activity (AChE). Moreover, hesperidin attenuated the depleted content of reduced glutathione (GSH) and elevated level of thiobarbituric acid reactive substances (TBARS) and also augmented lipid alteration significantly following ICV-STZ injection. We also demonstrated that the flavonoid hesperidin modulates neuronal cell death by inhibiting the overexpression of inflammatory markers like nuclear factor κB, inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein positive astrocytes. The results from the present study open the possibility of using flavonoids for potential new therapeutic strategies for sporadic dementia of Alzheimer's disease.

Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats.

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2h followed by 22h reperfusion in Wistar male rats (250-280g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1ß, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient.

Cathinone, an active principle of Catha edulis, accelerates oxidative stress in the limbic area of swiss albino mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cathinone hydrochloride is an active principle of the khat plant (Catha edulis) that produces pleasurable and stimulating effects in khat chewers. To the best of our knowledge no data of cathinone on oxidative stress in limbic areas of mice is available. This is the first study of cathinone on oxidative stress in limbic areas of the brain in Swiss albino male mice. MATERIALS AND METHODS: The animals were divided into four groups. Group-I was the control group and received vehicle, while groups-II to IV received (-)-cathinone hydrochloride (0.125, 0.25 and 0.5 mg/kg body wt., i.p.) once daily for 15 days. RESULTS: The level of lipid peroxidation (LPO) was elevated dose-dependently and was significant (p<0.05, p<0.01) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. In contrast, the content of reduced glutathione (GSH) was decreased significantly (p<0.01, p<0.001) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. The activity of antioxidant enzymes (GPx, GR, GST, CAT, and SOD) was also decreased dose-dependently: the decreased activity of GPx, GR, catalase and SOD was significant with doses of 0.25 and 0.5 mg of cathinone as compared to control group, while the activity of GST was decreased dose-dependently and was significant with 0.5mg of cathinone as compared to control group. CONCLUSIONS: The results indicate that the cathinone generated oxidative stress hampered antioxidant enzymes, glutathione and lipid peroxidation.

Pluchea lanceolata protects against Benzo(a) pyrene induced renal toxicity and loss of DNA integrity.

Evidence from epidemiological, experimental and clinical trial data indicates that a plant based diet can reduce the risk of chronic diseases and reduces toxic effects. In the present study, we report the antioxidant and anticlastogenic activity of Pluchea lanceolata (PL), an important medicinal plant, in both in vitro and in vivo model. Benzo(a)pyrene (B(a)P) administration leads to depletion of renal glutathione and its metabolizing enzymes. Pretreatment with PL (100 and 200 mg /kg b.wt) restored renal glutathione content and its dependent enzymes significantly (p<0.001) with simultaneous increase in catalase(CAT), quinone reductase(QR) in mouse kidney. Prophylactic administration of PL prior to B (a) P administration significantly decreased the malondialdehyde(MDA), H2O2 and xanthineoxidase (XO) levels at a significance of p<0.001, at both the doses. PL extract pretreated groups showed marked inhibition in B(a)P induced micronuclei formation in mouse bone marrow cells with simultaneous restoration of DNA integrity, viz. alkaline unwinding assay and DNA damage shown by gel-electrophoresis. HPTLC confirms the presence of quercetin in plant extract which could be responsible for PL protecting efficacy. In conclusion, the present findings strongly support the antioxidant efficacy of PL, possibly by modulation of antioxidant armory.

Delayed administration of zingerone mitigates the behavioral and histological alteration via repression of oxidative stress and intrinsic programmed cell death in focal transient ischemic rats.

The neuronal mitochondria succumb to ischemia-reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia-reperfusion-induced oxidative stress and molecular events in iPCD 24 h post ischemia-reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100 mg/kg b.wt. orally twice) at 5 h and 12 h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p<0.001). Zingerone treatment significantly improved behavioral outputs (p<0.05) and histological architecture (p<0.001) by reducing lipid peroxidation (p<0.01), augmenting the reduced glutathione content (p<0.01) and restoring Na(+)-K(+) ATPase and superoxide dismutase activities (p<0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p<0.05) and succeeded in lowering the expressions of pro-apoptotic proteins - Apaf-1 and Bax (p<0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress.

Isolation and screening of bioactive principle from Chaetomorpha antennina against certain bacterial strains.

Microbial pathogens develop resistance to a particular antibiotic after repeated administration during the treatment of infectious diseases. Moreover, multiple drug resistance is a very common problem especially in hospital acquired infections. Therefore, it is necessary to find out alternative antibacterial drugs and the present trend is focused on seaweeds. This preliminary research work was carried out to find out the antibacterial activity of petroleum ether extract of Chaetomorpha antennina. The extracts were tested against Staphylococcus aureus MTCC 121, Bacillus cereus MTCC 492, Bacillus subtilis MTCC 441, Klebsiella pneumoniae MTCC 530, Escherichia coli MTCC 443 and Pseudomonas aeruginosa MTCC 779 by agar well diffusion technique. It was observed that petroleum ether extract showed prominent zone of inhibition against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus even at 50 µg/ml concentration. The maximum spectrum of activity was observed against Staphylococcus aureus ranged from 7.3 ± 0.8 to 18 ± 2.4 mm at the concentration 50 to 500 µg/ml, respectively. Hence the most susceptible bacterium was Staphylococcus aureus among the tested organisms. However, Escherichia coli and Pseudomonas aeruginosa are also susceptible. But the Bacillus cereus and Klebsiella pneumoniae are resistant against the tested extract.

Taurine ameliorates neurobehavioral, neurochemical and immunohistochemical changes in sporadic dementia of Alzheimer's type (SDAT) caused by intracerebroventricular streptozotocin in rats.

Oxidative loads in the brain are involved in age related impairments like learning and memory as well as neurodegeneration. Taurine, the most abundant free amino acid in humans has many potential health benefits through its anti-oxidant and anti-inflammatory properties. Therefore, we investigated the neuroprotective potential of taurine on oxidative stress, neuronal loss and memory impairments in streptozotocin model of cognitive impairments in rats. The cognitive impairment was developed by giving single intracerebroventricular (ICV) injection of streptozotocin (STZ) 3 mg/kg body weight bilaterally. An increased latency and path length was observed in ICV-STZ group animals as compared to sham group animals and these were inhibited significantly in STZ group pre-treated with taurine (50 mg/kg body weight orally once daily for 15 days). Moreover, the significantly depleted content of GSH and elevated level of thiobarbituric acid reactive substances (TBARS) in ICV-STZ group animals were protected significantly with pre-treatment of taurine. The activity of antioxidant enzymes, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase was decreased in STZ group as compared to sham group and pre-treatment of STZ group with taurine has protected their activities significantly. Furthermore, the increased activity of acetylcholine esterase and decreased expression of choline acetyl transferase were attenuated by the pre-treatment of taurine. Taurine also protected the morphology of the hippocampal pyramidal neurons. This study concludes that the prophylactic intervention of taurine may be used to prevent the deterioration of cognitive functions and neurobehavioral activities, often associated with the generation of free radicals.

Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20mg/kgb wt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3mg/kgb wt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1ß levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT).

Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.

Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment.