Effect of piperine on pentobarbitone induced hypnosis in rats

Piperine (1-peperoyl piperidine), a major alkaloid isolated from Piper nigrum Linn, potentiated pentobarbitone sleeping time in dose dependant manner, with peak effect at 30 min. Blood and brain pentobarbitone levels were higher in piperine treated animals. Piperine treatment in rats, treated chronically with phenobarbitone, significantly potentiated pentobarbitone sleeping time, as compared to the controls. There was no alteration in barbital sodium sleeping time. It is possible that, piperine inhibits liver microsomal enzyme system and thereby potentiates the pentobarbitone sleeping time.     

Variation in pentobarbitone sleeping time in mice. 2. Variables affecting test results

The effect of some environmental factors on the pentobarbitone sleeping time (PST) in inbred strains of mice has been investigated. Age, dose level and fasting before the test significantly altered the PST while the source of the drug and regular handling of the mice had no effect. None of these factors affected strains differentially. Unsystematic effects such as litter differences contributed only a small proportion of the total variation in the experiments. The strain rankings were different from those obtained in some previous experiments. The effects of some of the environmental factors on the PST did not always agree with previous work. The implications of these results for the design of similar experiments and the relevance of baseline values in laboratory animals are discussed.     

CNS activity of Vitex negundo Linn. in mice

Methanolic extract (ME) of the leaves of V. negundo potentiated significantly the sleeping time induced by pentobarbitone sodium, diazepam and chlorpromazine in mice. ME possesses analgesic properties and potentiated analgesia induced by morphine and pethidine. ME also showed significant protection against strychnine and leptazole induced convulsions. The results suggest that ME exhibits CNS depressant activity in a dose dependent manner.     

Neurophysiological alterations following fluvalinate administration in mice.

Median lethal dose (LD50) of fluvalinate (Marvik 25EC) was 105 (94.6-116.5 mg/kg, ip) in albino mice. Gross observable signs were dose dependent and indicative of central and peripheral nervous system stimulation. Fluvalinate, at 10.5 and 21.0 mg/kg, ip doses in mice, facilitated maximal electroshock seizures, reduced reaction time in analgesic test and enhanced duration of ether anaesthesia. Acute and subacute (7 days) treatment at lower and higher doses enhanced pentobarbitone sleeping time. Acute and subacute treatment (7 days) with phenobarbitone (50 mg/kg, ip) prior to fluvalinate enhanced toxicity of fluvalinate.     

Variation in pentobarbitone sleeping time in mice. 1. Strain and sex differences

A set of 23 inbred strains of mice was tested for their sleeping time under sodium pentobarbitone anaesthetic. Highly significant strain differences were found. Estimates of the proportion of the variation accounted for by genetic differences ranged from 28% to 42%. In general, males slept longer than females but the size of the sex differences was not consistent across strains. Sleeping times on different test days also varied, indicating that environmental factors were affecting the results. A specially designed experiment failed to detect any differences in within-strain variation.     

Role of 5-hydroxytryptamine in Moringa oleifera induced potentiation of pentobarbitone hypnosis in albino rats

The role of 5-hydroxytryptamine (5-HT) in pentobarbitone (PB) sleeping time, gross behaviour, electrical activity of the brain and serum 5-HT level was studied in Holtzman strain adult albino rats following treatment with M. oleifera (MO). MO (350mg/kg) caused inhibition of awareness, touch response, motor activity, righting reflex, and grip strength. It significantly increased the PB sleeping time, serum 5-HT level (P<0.001) and alpha-wave activity. These observations indicate that the aqueous extract of MO potentiated PB induced sleeping time and increased the alpha-wave activity through 5-HT.     

Effects of phenobarbitone on hepatic microsomal enzyme activity and liver blood flow in spontaneously hypertensive rats.

Hepatic microsomal enzyme activity, liver blood flow and pentobarbitone sleeping time were determined in spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR) after pretreatment with saline or phenobarbitone. In NR and SHR the increases in total liver blood flow produced by phenobarbitone were sufficient to maintain liver perfusion despite the increase in liver weight and in both strains of rat the increase was entirely due to increased portal venous return. Saline pretreated SHR had shorter pentobarbitone sleeping times than control NR and their livers had greater total cytochrome c reductase activities and total microsomal protein than those of NR but cytochrome P-450 contents were not significantly different. Phenobarbitone significantly shortened sleeping times in both strains but NR still slept longer than SHR. Total microsomal protein, cytochrome P-450 content and cytochrome c reductase activity were increased by phenobarbitone in both SHR and NR but the increases in cytochrome P-450 and cytochrome c reductase were greater in the hypertensive rats.     

Influence of Chlorella powder intake during swimming stress in mice

We used the forced swimming test to investigate the influence of Chlorella powder intake during muscle stress training in mice. After day 14, swimming time was about 2-fold longer for Chlorella intake mice than for control swimming mice. Microarray analysis revealed that the global gene expression profile of muscle from the Chlorella intake mice was similar to that of muscle from the intact (non-swimming) mice, and the profile of these two groups differed from that of the control (swimming) mice. Gene ontology and pathway analyses of gene expression data showed that oxidoreductase activity and the leukotriene synthesis pathway were repressed in the Chlorella intake mice following the swimming test. In addition, measurements of free fatty acids, glucose, triglycerides, and lactic acid in the blood of Chlorella intake mice were higher than that of control mice. These findings suggest that metabolism in tissues is altered by Chlorella intake.     

CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats

Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.     

Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK

It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac remodeling. 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. To evaluate the molecular mechanism underlying swimming stress-induced cardiac remodeling, we examined the role of 14-3-3 protein and MAPK pathway by pharmacological and genetic means using transgenic mice with cardiac-specific expression of dominant-negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38alpha/beta MAPK (DNp38alpha and DNp38beta) mice. p38 MAPK activation was earlier, more marked, and longer in the myocardium of the TG group compared with that of the nontransgenic (NTG) group after swimming stress, whereas JNK activation was detected on day 5 and decreased afterward. In contrast, ERK1/2 was not activated after swimming stress in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were greatly increased in the TG group compared with those in the NTG group. Moreover, we found a significant correlation between p38 MAPK activation and apoptosis in the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic peptide expression. In contrast, DNp38alpha and DNp38beta mice exhibited reduced mortality and increased resistance to cardiac remodeling after 28 days of swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in the survival rate in the TG group. These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress.     

The comparison of immobility time in experimental rat swimming models

Rat swimming models have been used in studies about stress and depression. However, there is no consensus about interpreting immobility (helplessness or adaptation) in the literature. In the present study, immobility time, glucose and glycogen mobilization, corticosterone and the effect of desipramine and diazepam were investigated in two different models: swimming stress and the forced swimming test. Immobility time was lower in swimming stress than in the forced swimming test. Both swimming models increased corticosterone levels in comparison with control animal levels. Moreover, swimming stress induced higher corticosterone levels than the forced swimming test did [F(2,14)=59.52; p<0.001]. Liver glycogen content values differed from one another (swimming stress相似文献   

Hepatoprotective and antioxidant activities of flowers of Calotropis procera (Ait) R. Br. in CCl4 induced hepatic damage

Hepatoprotective activity of 70% ethanolic extract of flowers of C. procera was studied against CCl4 induced hepatic injury in albino rats and mice. In addition, antioxidant activity was studied by in vitro models. Pre-treatment with 70% ethanolic extract (CPA) reduced the biochemical markers of hepatic injury like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, cholesterol, HDL and tissue glutathione (GSH) levels. Similarly pretreatment with CPA reduced the CCl4 induced elevation in the pentobarbitone sleeping time. Histopathological observations also revealed that pretreatment with CPA protected the animals from CCl4 induced liver damage. CPA demonstrated dose dependant reduction in the in vitro and in vivo lipid peroxidation induced by CCl4. In addition it showed dose dependant free radical scavenging activity. The results indicate that flowers of C. procera possess hepatoprotective property possibly because of its anti-oxidant activity. This property may be attributed to the quercetin related flavonoids present in the flowers of Calotropis procera.     

Attenuated stress-induced catecholamine release in mice lacking the vasopressin V1b receptor

Vasopressin V(1b) receptor is specifically expressed in the pituitary and mediates adrenocorticotropin release, thereby regulating stress responses via its corticotropin releasing factor-like action. In the present study we examined catecholamine release in response to two types of stress in mice lacking the V(1b) receptor gene (V(1b)R(-/-) mice) vs. wild-type mice. There were no significant differences in the basal plasma levels of catecholamines between the two genotypes. In response to stress induced by forced swimming, norepinephrine (NE), but not epinephrine (E) or dopamine (DA), was increased in wild-type mice, whereas the increases in NE and DA were not observed in V(1b)R(-/-) mice. In wild-type mice, E, but not NE or DA, was increased in response to social isolation stress, whereas the increase in E was not observed in V(1b)R(-/-) mice. These results suggest that the V(1b) receptor regulates stress-induced catecholamine release. Because it has been suggested that arginine-vasopressin (AVP) is related to the development of depression, we also evaluated immobility time in the forced swimming test, and we found no significant change in V(1b)R(-/-) mice. Taken together, these findings suggest that, in addition to the previously elucidated effect on the hypothalamic-pituitary-adrenal axis, vasopressin activity via V(1b) receptors regulates stress-induced catecholamine release.     

五加皮及其混乱品种的药理作用研究

本文对刺五加、细柱五加、红毛五加、香加皮的醇提物及红毛五加水提物五种药液的药理作用进行了比较研究。结果如下：（１）分组腹腔注射五种药液对巴豆油引起的小鼠耳部炎症均有显著的抑制作用,其中以红毛五加水提物的抗炎作用最强。（２）灌胃给五种药液只有红毛五加水提物和刺五加醇提物能明显延长小鼠游泳时间。（３）对环磷酰胺所致白细胞数减少的小鼠分组灌胃五种药液,结果表明红毛五加水提物、刺五加醇提物及细柱五加醇提物均有明显的升白作用。（４）在研究五种药液影响巴比妥钠诱导小鼠睡眠的实验中,结果显示灌胃刺五加醇提物能明显延长小鼠的睡眠时间,香加皮和红毛五抓醇提物则明显缩短小鼠的睡眠时间,细住五加醇提物和红毛五加水提物对小鼠睡眠时间无影响。     

Pharmacological and haematological study of shol fish (Channa striatus) skin extract on experimental animal

Snake head fish Channa striatus (locally called 'shol') skin extract (SFSE) was examined for certain pharmacological and haematological effects on experimental animals. LD50 of SFSE was found to be 6 mg/20gm (iv) in male albino mice. SFSE potentiated pentobarbitone induced sleeping time in male albino mice and produced hypothermia. Low dose of SFSE decreased respiratory rate in rat and guineapig and high dose produced apnoea leading to death. On isolated toad and guineapig heart, SFSE significantly decreased rate and amplitude of contraction leading to temporary blockade, which returned after repeated wash. On isolated nerve muscle preparations, SFSE produced irreversible blockade of twitch response. SFSE induced quick contraction on isolated guineapig ileum, which was antagonised by atropine and cyproheptadine. SFSE did not possess haemolytic and haemorrhagic activity but produced anaemia in male albino mice. A neurotoxic compound (fluoroscent and ninhydrin positive) was isolated from SFSE by thin layer chromatography. This compound (CS-NT) was lethal in male albino mice, produced death by apnoea in rat and produced irreversible blockade of isolated nerve-muscle preparation. This study confirms that the skin of Channa striatus possesses toxic, and lethal components, which needs further detailed study.     

Involvement of diazepam binding inhibitor and its fragment octadecaneuropeptide in social isolation stress-induced decrease in pentobarbital sleep in mice.

Diazepam binding inhibitor (DBI) and its fragment, octadecaneuropeptide (ODN), are putative endogenous ligands for benzodiazepine (BZD) receptors and have been shown to act as an inverse BZD receptor agonist in the brain. A previous study suggested that the social isolation stress-induced decrease in pentobarbital sleep in mice was partly due to endogenous substances with an inverse BZD receptor agonist-like property. In this study, we examined the effects of DBI and ODN on pentobarbital sleep in group-housed and socially isolated mice to test the possible involvement of DBI and ODN in a social isolation-induced decrease in pentobarbital sleep. The socially isolated mice showed significantly shorter durations of pentobarbital (50 mg/kg, intraperitoneally, i. p.) sleep compared to the group-housed animals. When injected intracerebroventricularly (i.c.v.), DBI and ODN (3 and 10 nmol) dose-dependently shortened the pentobarbital-induced sleeping time in group-housed mice at the same dose range, but these peptides had no effect on the sleeping time in socially isolated animals. In contrast, flumazenil (16.5-33 nmol, i.c.v.), a BZD receptor antagonist, reversed the pentobarbital sleeping time in socially isolated mice to the level of group-housed animals without affecting the sleeping time in group-housed animals. The effects of DBI and ODN in group-housed mice were significantly blocked by flumazenil (33 nmol, i.c.v.). Moreover, the effect of flumazenil in socially isolated mice was significantly attenuated by DBI and ODN (10 nmol, i.c.v.). These results suggest that the changes in the activity of DBI and/or ODN are partly involved in the social isolation-induced decrease in the hypnotic action of pentobarbital in mice.     

Enhancement of pentobarbital effect by continuous administration of morphine in the mouse

These studies demonstrated that continuous morphine treatment from implantation of a 75 mg morphine pellet for 3 days potentiated pentobarbital narcosis and enhanced pentobarbital hypothermia. In the morphine implant mice, sleeping time after two different doses of pentobarbital was greater than 2.5 × the sleeping time in placebo pellet implant animals and also greater than sleeping time in animals treated acutely with morphine prior to pentobarbital. Moreover, in the morphine implant mice both the degree and duration of pentobarbital induced hypothermia were enhanced. The above findings were due to slower rate of metabolism of pentobarbital as evidenced by inhibition of hepatic N-demethylation, and higher levels of brain and serum pentobarbital in the morphine implant mice compared to both placebo and acute morphine mice.     

白灵菇多糖对运动小鼠氧化应激的影响

体外研究表明,白灵菇多糖具有较高的清除自由基能力。然而,白灵菇多糖在体内对运动引起的氧化应激的影响尚不清楚。本研究将100只SPF级雄性昆明小鼠随机分为5组,低剂量组、中剂量组和高剂量组昆明小鼠分别按照50 mg·kg^-1·d^-1、100 mg·kg^-1·d^-1和200 mg·kg^-1·d^-1的剂量灌胃白灵菇多糖溶液,对照组和模型组昆明小鼠灌胃等体积的蒸馏水,连续灌胃4周。研究显示,白灵菇多糖溶液以浓度依赖性方式提高了小鼠的力竭游泳时间(p<0.05)。白灵菇多糖以浓度依赖性方式降低了小鼠血清AST、ALT和CK水平,并显著减少了骨骼肌的病理变化(p<0.05)。白灵菇多糖以剂量依赖方式升高力竭游泳小鼠体内SOD、CAT和GSH-PX水平,并降低了MDA水平(p<0.05)。此外,对小鼠灌胃白灵菇多糖可以剂量依赖方式提高小鼠血清总抗氧化活性(p<0.05)。上述研究表明,白灵菇多糖可有效提高力竭游泳小鼠的抗疲劳能力,减轻运动引起的心肌、肝脏、骨骼肌和氧化应激损伤,提高机体的抗氧化能力。     

植物提取物槲皮素调节小鼠的能量代谢和氧化应激

为了探讨植物提取物槲皮素对负重游泳小鼠的能量代谢和氧化应激的影响,本研究将45只SPF级雄性昆明小鼠随机分为正常对照组、游泳组和槲皮素组,每组15只。槲皮素组小鼠喂养2 g/kg的槲皮素饲料,其他组小鼠喂养标准饲料,共喂养14 d。然后将游泳组和槲皮素组小鼠按照体重的3%进行负重游泳1 h,测定各组小鼠的血糖、乳酸、尿素氮、游离脂肪酸、琥珀酸脱氢酶、三磷酸腺苷、丙二醛、谷胱甘肽过氧化物酶和总抗氧化活性。结果显示,负重游泳后,槲皮素组血清乳酸和尿素氮水平显著低于游泳组,并且槲皮素组游离脂肪酸水平显著高于游泳组。负重游泳后,游泳组小鼠的肝脏和肌肉组织中的琥珀酸脱氢酶含量均显著降低,槲皮素组小鼠游泳后未见明显降低。负重游泳后,游泳组小鼠肌肉组织中的ATP酶活性显著降低,槲皮素组小鼠游泳后未见明显降低。负重游泳后,槲皮素组的丙二醛含量显著低于游泳组。游泳组和槲皮素组小鼠负重游泳后的谷胱甘肽过氧化物酶含量均显著降低,槲皮素组小鼠的谷胱甘肽过氧化物酶含量未见明显降低。游泳组小鼠血清总抗氧化活性显著低于对照组,而槲皮素组与对照组无显著差异。本研究初步表明,槲皮素可调节负重游泳小鼠的能量代谢来起到抗疲劳作用,主要机制与增加脂肪动员、抑制蛋白质分解和加强三羧酸循环有关。另外,槲皮素可通过抑制脂质过氧化、清除超氧阴离子自由基来防止运动过程中的氧化应激损伤。     

Effect of cadmium on ethanol induced sleeping time in mice

The effect of cadmium on sleeping time induced by ethanol was studied in mice. When 0.25, 2.5 or 5.0 mg/kg of CdCl₂ was injected intraperitoneally (i.p.), the ethanol induced sleeping time was enhanced by 50 %, 100 % or 150 % from that of saline treated mice. The enhancement of ethanol induced sleeping time by cadmium was completely blocked by intracerebroventricular (i.vt.) pretreatment with CDTA, an agent that chelates cadmium ion. This indicates that the ethanol induced sleeping time was enhanced by a part of cadmium which passed through blood brain barrier after the i.p. injection.On the other hand, the ethanol induced sleeping time was also increased by 50 % with i.vt. injection of L-serotonin but not altered with L-dopamine or L-norepinephrine. In addition to this, i.vt. injection of L-serotonin plus L-norepinephrine enhanced by 170 % the ethanol induced sleeping time. Furthermore, the enhancement of ethanol induced sleeping time by cadmium was potentiated by i.vt. treatment of L-serotonin or L-norepinephrine but not by L-dopamine. These results suggest that the enhancement of ethanol induced sleeping time by cadmium may be caused by an increase in L-serotonin levels or both L-serotonin and L-norepinephrine levels but not by L-dopamine levels in brain of mouse.