Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Nigella sativa (NS) extract on memory performance and its possible mechanisms in scopolamine (Sco)-induced spatial memory impairment model using Morris water maze test.</p><p><b>METHODS</b>Thirty-two male Wistar rats were randomly divided into four groups. The control group received saline instead of both NS extract and Sco. The Sco group was treated by saline for two weeks, and was injected by Sco (2 mg/kg, intraperitoneally) 30 min before each trail in Morris water maze test. Sco+NS 200 and Sco+NS 400 groups were daily treated by 200 or 400 mg/kg of NS (intraperitoneally) for two weeks, respectively, and were finally injected by Sco 30 min before Morris water maze test. The brains of animals were removed to determine the acetylcholinesterase (AChE) activity and oxidative stress criteria in cortical tissues.</p><p><b>RESULTS</b>Time latency and path length in the Sco group were significantly higher than in the control group (P<0.01), while the Sco+NS 400 group showed a significantly shorter traveled path length and time latency compared with the Sco group (P<0.01). AChE activity in the cortical tissues of the Sco group was significantly higher than the control group (P<0.01), while AChE activity in the Sco+NS 200 and Sco+NS 400 groups was lower than the Sco group (P<0.01). Following Sco administration, malondialdehyde (MDA) concentrations were increased (P<0.01) in comparison with the control group, while cortical total thiol content decreased (P<0.01). Pretreatment with extracts caused a significant elevation in cortical total thiol content (P<0.01) and reduction in cortical MDA concentration (P<0.01) compared with the Sco group.</p><p><b>CONCLUSIONS</b>Hydro-alcoholic extract of NS prevents Sco-induced spatial memory deficits and decreases the AChE activity as well as oxidative stress of brain tissues in rats. Our results support the traditional belief about the beneficial effects of NS in nervous system. Moreover, further investigations are needed for better understanding of this protective effect.</p>

effects of nigella sativa hydro-alcoholic extract on memory and brain tissues oxidative damage after repeated seizures in rats

Regarding the therapeutic properties of Nigella sativa [NS], the effects of the plant hydro–alcoholic extract on learning, memory and brain tissues oxidative damage were investigated in penthylenetetrazole [PTZ]-induced repeated seizures. There were 4 experimental groups including: 1- control group; received saline, 2- PTZ group; received saline and PTZ [50 mg/Kg, i.p], 3- PTZ-NS 200 and 4- PTZ-NS 400 ; received 200 and 400 mg/Kg of NS extract respectively, before PTZ injection in 5 consecutive days. Seizure scores were lower in PTZ–NS 200 and 400, furthermore the seizure onset latencies were higher in these groups than PTZ group [P<0.05 and P<0.01]. In Morris water maze, the time spent in target quadrant by PTZ group was lower than control group [P<0.05]; while, 400 mg/Kg of the extract increased it [P<0.01]. In the passive avoidance test, delay time to enter the dark by PTZ group was lower than control at 1 and 24 hours after training [P<0.01 - P<0.001]; while, 400 mg/Kg of the extract increased it [P<0.05]. The total thiol concentration in hippocampal and cortical tissues of PTZ group was reduced while, MDA concentration was higher than control [p<0.05 - p<0.001]. Administration of the extract increased the total thiol and decreased the MDA concentrations [p<0.01 - p<0.001]. It is concluded that the hydro-alcoholic extract of NS possess beneficial effects on learning and memory impairments in repeated seizures model which is accompanied by antioxidant effects in the brain

The Effects of Soy Extract on Spatial Learning and Memory Damage Induced by Global Ischemia in Ovariectomised Rats

Background: The effects of soy extract on memory as well as the oxidative damage to brain tissue induced by ischemia was investigated in ovariectomised (OVX) rats. Methods: The rats were divided into: 1) Sham; 2) OVX; 3) Sham‑Ischemia; 4) OVX‑Ischemia; 5) OVX-‑Ischemia-‑S 20; and 6) OVX-‑Ischemia-‑S 60. The common carotid artery was occluded (30 minutes), and it was then re-‑perfused. The OVX-‑Ischemia-‑S 20 and OVX-‑Ischemia-‑S 60 groups received 20 or 60 mg/kg of soy extract for eight weeks before the ischemia. Results: The Sham-‑Ischemia and OVX-‑Ischemia groups took a longer time to reach the platform while, spent a shorter time in the target quadrant (Q1) than the Sham and OVX. The escape latencies in the OVX-‑Ischemia-‑S 20 and OVX-‑Ischemia-‑S 60 groups were lower while, time spent in the Q1 was higher than that of the OVX-‑Ischemia. In the rotarod test, there were no significant differences between the groups. The hippocampal concentrations of malondialdehyde (MDA) in the Sham-‑Ischemia and OVX-‑Ischemia groups were higher than the Sham and OVX. Pre-‑treatment by 20 and 60 mg/kg of the extract reduced the MDA. Conclusion: It is suggested that soy prevents memory impairment and brain tissue oxidative damage due to ischemia in OVX rats.

Single dose effect of diazinon on biochemical parameters in testis tissue of adult rats and the protective effect of vitamin E

Diazinon [DZN] is an organophosphate pesticide that widely used for agricultural pest control all over the world. DZN affects target organs including reproductive system by inhibiting the activity of acetylcholinesterase and inducing oxidative stress. Vitamin E [alpha-tocopherol] is a strong antioxidant which inhibits free radicals, and probably can reduce lipid perxidation effectively in biological systems. The present study, aimed to evaluate the effects of DZN on malondialdehyde [MDA] and glutathione [GSH] levels in testis of rats and protective effect of vitamin E. In this experimental study, thirty adult male Wistar rats [200-250 gr] were divided into 5 groups [n= 6]: control group [did not receive any material], sham group [received only pure olive oil], experimental group 1 [DZN, 60 mg/kg], experimental group 2 [Vit E, 200 mg/kg] and experimental group 3 [DZN+Vit E, with the same dose]. All groups were sacrificed after 6 weeks and right testis was used to measure the MDA and GSH levels. The amount of MDA was determined by the thiobarbituric acid assay and 5, 5-Dithio-bis [2nitrobenzoic acid] DTNB-recycling protocol was used for GSH assay. The results showed that DZN increased MDA level [p<0.001] and reduced GSH level [p<0.001]. Administration of DZN plus vitamin E decreased the MDA level [p<0.001] and increased GSH level [p=0.001]. DZN induced lipid peroxidation in the testis of rats. Vitamin E by its antioxidant activity was able to improve the toxic effect of DZN

[Assessment of erythrocyte and serum cholinesterase activity in male rats treated with diazinon, and protective role of vitamin E]

Background: Diazinon [DZN] is an organophosphate [OP] that inhibit cholinesterase activity and induce oxidative stress in the target tissues such as the the reproductive system .The aim of present study was to evaluate the effects of diazinon on cholinesterase activity in blood serum and erythrocytes of male rats and to assess the protective role of vitamin E.

Material and Methods: In this experimental study, thirty adult male wistar rats [200 - 250 gr] were divided into 5 groups [n = 6]: control group [did not receive any material], sham group [received only pure olive oil], experimental group 1 [DZN, 60 mg/kg], experimental group 2 [received DZN+Vit E daily, with the same dose] and experimental group 3[Vit E 200 mg/kg]. DZN and solvent was injected intraperitoneally [IP] and vitamin E was administrated by gavage. After 6 weeks, 3 ml blood from the heart tissue was taken and titrimetric and Ellman's method respectively was used for serum and erythrocyte cholinesterases activity evaluation. Data were analyzed using SPSS software. P<0.05 value was taken as statistically significant.

Results: The results showed that diazinon, reduced activity of acetylcholinesterase [P= 0.000] and pseudocholinesterase [P=0.01] in experimental group 1 compared to the control group. Inhibition in erythrocyte and serum cholinesterase activity was not recovered in experimental group 2 [use of diazinon plus vitamin E diazinon].

Conclusion: According to inhibit the activity of two important enzymes of erythrocyte and serum cholinesterase in rats treated with diazinon, there are possibility of cytotoxicity at farmers and people who are in contact with these compounds. On the other hand, cholinesterase activity did not recovered by vitamin E probably due to the competitive nature of enzyme inhibition by diazinon. Therefore, care should be taken to prevent from entering toxin to the body.

Effect of zirconium dioxide nanoparticles on glutathione peroxidase enzyme in PC12 and N2a cell lines

Today, special attention is paid to the use of zirconium dioxide nanoparticle [nano-ZrO[2]], a neutral bioceramic metal, particularly for drug and gene delivery in medicine. However, there are some reports implying that use of nano-ZrO[2] is associated with cytotoxic effects like inhibiting the cell proliferation, DNA damage and apoptosis. In the present study, we examined whether nano-ZrO[2] alters cell viability and glutathione peroxidase [GPx] activity in two neuronal cell lines. The PC12 and N2a cells were cultured in the absence or presence of varying concentrations [31.25-2000 micro g/mL] of nano-ZrO[2] for 12, 24 or 48 h. The cell viability was evaluated using 3-[4, 5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium [MTS] assay and GPx activity was determined by quantifying the rate of oxidation of the reduced glutathione to the oxidized glutathione. Nano-ZrO[2] caused a significant reduction in cell viability and GPx activity after 12, 24 and 48 h, as compared with control group. These effects were concentration dependent and started from 250 micro g/mL. The present study demonstrated that nano-ZrO[2], at concentrations of > 250 micro g/mL, has antiproliferative effects via reducing the cell defense mechanism against oxidative stress

Potentiating effects of Lactuca sativa on pentobarbital-induced sleep

Traditionally, Lactuca sativa [lettuce] has been recommended for its hypnotic property. The present study was planned to investigate sleep-prolonging effect of this plant. The hydro-alcoholic extract [HAE] of lettuce and its water fraction [WF], ethyl acetate fraction [EAF], and n-butanol fraction [NBF] were administrated [IP] to mice 30 min before the pentobarbital injection. Moreover, both in-vivo and in-vitro toxicity of the extracts were determined. The quality of HAE and NBF was also evaluated using HPLC fingerprint. The HAE prolonged the pentobarbital-induced sleep duration at dose of 400 mg/Kg. The NBF was the only fraction which could increase the sleep duration and decrease sleep latency. The effects of NBF were comparable to those of induced by diazepam. The LD[50]-value for HAE was found to be 4.8 g/Kg. No neurotoxic effect was observed either by HAE or by its fractions in cultured PC12 neuron-like cells. The results suggest that lettuce potentiates pentobarbital hypnosis without major toxic effect. The main component[s] responsible for this effect is most likely to be non-polar agent[s] which found in NBF of this plant

Effects of rutin on oxidative stress in mice with kainic acid-induced seizure / 中西医结合学报

<p><b>OBJECTIVE</b>Flavonoids are present in foods such as fruits and vegetables. Several studies have demonstrated a relationship between the consumption of flavonoid-rich foods and prevention of human disease, including neurodegenerative disorders. We assessed the effect of rutin (quercetin-3-O-rutinoside) on oxidative stress in kainic acid (KA)-induced seizure.</p><p><b>METHODS</b>Thirty-six BALB/c mice were randomly divided into three groups. In the control group, saline (intra-peritoneal, i.p.) was administered for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of saline. In rutin groups, mice were pretreated with rutin (100 and 200 mg/kg, i.p.) for 7 d, and on the last day, KA (10 mg/kg, i.p.) was injected 30 min after administration of rutin. Subsequently, behavioural changes were observed in mice. Lipid peroxidation and oxidative stress were measured respectively in the early and late phases after KA-induced seizures.</p><p><b>RESULTS</b>Seizure scores in the rutin groups were significantly lower than those in the control group (P < 0.01). Furthermore, rutin dose-dependently inhibited the number of wet-dog shakes (WDS) (P < 0.05). Malondialdehyde level in the hippocampus of the rutin groups was significantly lower than that in the hippocampus of the control group on days 1 and 21 after KA administration. In the rutin groups, the thiol levels observed on day 1 after KA administration were higher than that in the control group (P < 0.01).</p><p><b>CONCLUSION</b>These results indicate that rutin has potential anticonvulsant and antioxidative activities against oxidative stress in KA-induced seizure in mice.</p>

Effects of Coriandrum sativum extracts on glucose/serum deprivationinduced neuronal cell death

This study was planned to investigate whether Coriandrum sativum [C. sativum] is capable of protecting neurons against glucose/serum deprivation [GSD]-induced cytotoxicity. The PC12 cells were cultivated for 24 h in standard media [high-glucose DMEM containing Fetal Bovine Serum] or for 6 h in GSD condition [glucose-free DMEM, without serum] in the absence or presence of various concentrations [0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml] of hydro-alcoholic extract [HAE], water fraction [WF], ethyl acetate fraction [EAF] or N-butanol fraction [NBF] of this plant. At the end of the treatments, the cell viability was determined using MTT assay. With the exception of 1.6 mg/ml of EAF or NBF which decreased cell survival, the HAE and its fractions exhibited no cytotoxicity under standard condition. Exposure of the cells to GSD condition showed 52% decrease in the viability. In this condition, the HAE, EAF and NBF not only failed to increase cell viability but also increased the toxicity. On the other hand, WF at 0.4, 0.8 and 1.6 mg/ml significantly attenuated the GSD-induced decrease in cell survival. The present study revealed that C. sativum bearing water-soluble compound[s] could induce neuroprotective activity. Also, we showed that some constituents from this plant may serve as cytotoxic agents under stressful conditions like hypoglycemia and serum limitation

Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells

The discovery and development of natural products with potent antioxidant properties has been one of the most interesting and promising approaches in the search for treatment of CNS injuries. The most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability resulting cellular dysfunction. Serum/glucose deprivation [SGD] has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Nigella sativa [N. sativa] seeds and thymoquinone [TQ], its most abundant constituent, have been shown to possess antiinflammatory, antioxidant, chemopreventive and anti-neoplastic effects both in vitro and in vivo. Therefore, in this study we investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12 cells under SGD condition. PC12 cells were cultured in DMEM medium containing 10% [v/v] fetal bovine serum, 100 units/ml penicillin, and 100 micro g/ml streptomycin. Initially cells were pretreated with different concentrations of N. sativa extract [NSE], [10, 50, 250 micro g/ml] and TQ [1, 5, 10 micro g/ml] for 6 h and then deprived of serum/glucose [SGD] for 18 h. The alkaline comet assay was used to evaluate the effect of these compounds on DNA damage following ischemic insult. The amount of DNA in the comet tail [% tail DNA] was measured as an indicator of DNA damage. A significant increase in the% tail DNA was seen in nuclei of cells following SGD induced DNA damage [p<0.001]. In the control groups, no significant difference was found in the% tail DNA between NSE- or TQ-pretreated and vehicle-pretreated PC12 cells [p>0.05]. NSE and TQ pretreatment resulted in a significant decrease in DNA damage following ischemic insult [p<0.001]. This suppression of DNA damage by NSE and TQ was found to be dose-dependent. These data indicate that NSE and TQ have a genoprotective property, as revealed by the comet assay, under SGD condition in PC12 cells

Effect of berberine on pentylenetetrazol-induced seizures in rats

Antiepileptic drugs [AEDs] that are usually used for treatment of epilepsy have substantial side effects and about 30% of patients continue to have seizures with current AEDs therapy. Some herbs which traditionally used in the management of seizures of many rural areas of the developing countries have shown anticonvulsant activity in modern pharmacological bioassays. The aim of the present study was to evaluate the effects of berberine, an alkaloid from Berberis vulgaris, on seizures induced by pentylenetetrazol [PTZ] in rats. Rats [n=6-7] received berberine [100, 200 and 400 mg/kg, i.p.], diazepam [4mg/kg, i.p. as positive control], and vehicle [saline] and then 30 min later PTZ [110mg/kg, i.p.] were injected. Behavioral responses of the animals to PTZ administration were evaluated using these criteria: latency to first minimal clonic seizure [MCS], incidence of MCS, latency to the first generalized tonic-clonic seizures [GTCS], incidence of GTCS, protection against GTCS and mortality. Intraperitoneal administration of lower doses of berberine [100 and 200 mg/kg] had no significant effects on minimal clonic seizures [MCS] and generalized tonic-clonic seizures [GTCS] latencies, while injection of 400 mg/kg caused significant increase in both MCS and GTCS latencies [p<0.05]. In this study diazepam, [4 mg/kg] 30 min prior to PTZ, significantly increased GTCS latency. Berberine at tested doses had no protection against mortality following PTZ administration. It can be concluded that berberine at high doses could be a useful protective agent in PTZinduced epileptic seizures in rats

Review of the pharmacological and toxicological effects of Salvia leriifolia

Salvia leriifolia Benth. [vernacular names such as Nuruozak and Jobleh] is a perennial herbaceous plant that grows exclusively in south and tropical regions of Khorasan and Semnan provinces, I. R. Iran. Unlike other species of Salvia genus, the chemical constituents of S. leriifolia are not well recognized. The stem oil of the plant consisted mainly both monoterpenes and sesquiterpenes, while in leaf and flower oils monoterpenes predominated over sesquiterpenes. In recent years, the different properties of this plant such as the attenuation of morphine dependence, hypoglycemic, antinociceptive and anti-inflammatory, antioxidant, antiischemia, anticonvulsant, antiulcer effects, antibacterial activities and antimutagenic effects were evaluated. These effects introduce this plant for more toxicological and clinical trials evaluations as a herbal medicine