A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover

Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence.     

Wound healing and protease inhibition activity of Bacoside‐A,isolated from Bacopa monnieri wettest

Bacopa monnieri (L.) Wettest. (Scrophulariaceae) is a well‐known medicinal herb. In the Indian system of medicine it is known as Brahmi (Sanskrit) and Indian water hyssop. Methanolic extract of Bacopa monnieri and its isolated constituent Bacoside‐A were screened for wound healing activity. Bacoside‐A was screened for wound healing activity by excision, incision and dead space wound on Swiss albino rats. Significant wound healing activity was observed in both extract and the Bacoside‐A treated groups. The SDS‐PAGE caseinolytic zymogram analysis of inhibition of matrix metalloproteases (MMPs) enzyme from the excision wound by Bacoside‐A, an isolated constituent, was done with the concentrations 100 and 200 μmg/ml. In Bacoside‐A treated groups, epithelialization of the excision wound was faster with a high rate (18.30 ± 0.01 days) of wound contraction. The tensile strength of the incision wound was increased (538.47 ± 0.14 g) in the Bacoside‐A treated group. In the dead space wound model, the weight of the granuloma was also increased (89.15 ± 0.08 g). The histological examination of the granuloma tissue of the Bacoside‐A treated group showed increased cross‐linking of collagen fibers and absence of monocytes. The wound healing activity of Bacoside‐A was more effective in various wound models compared to the standard skin ointment Nitrofurazone. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of crocus sativus L. (saffron) stigma and its constituents,crocin and safranal,on morphine withdrawal syndrome in mice

Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine‐withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5 h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3 mg/kg) or normal saline. Naloxone was injected (5 mg/kg i.p.) 2 h after the final dose of morphine and the number of episodes of jumping during 30 mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30 mm prior and 1 and 2 h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320 mg/kg) and the ethanolic extract decreased it in the dose of 800 mg/kg in open field test. But crocin and the dose of 400 mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome. Copyright © 2009 John Wiley & Sons, Ltd.     

Bacopa monnieri‐Induced Protective Autophagy Inhibits Benzo[a]pyrene‐Mediated Apoptosis

Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P‐induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P‐induced apoptosis through autophagy induction. Pretreatment with BM rescued the reduction in cell viability in B[a]P‐treated human keratinocytes (HaCaT) cells indicating the cytoprotective potential of BM against B[a]P. Moreover, BM was found to inhibit B[a]P‐mediated reactive oxygen species (ROS)‐induced apoptosis activation in HaCaT cells. Furthermore, BM was found to preserve mitochondrial membrane potential and inhibited release of cytochrome c in B[a]P‐treated HaCaT cells. Bacopa monnieri induced protective autophagy; we knocked down Beclin‐1, and data showed that BM was unable to protect from B[a]P‐induced mitochondrial ROS‐mediated apoptosis in Beclin‐1‐deficient HaCaT cells. Moreover, we established that B[a]P‐induced damaged mitochondria were found to colocalize and degraded within autolysosomes in order to protect HaCaT cells from mitochondrial injury. In conclusion, B[a]P‐induced apoptosis was rescued by BM treatment and provided cytoprotection through Beclin‐1‐dependent autophagy activation. Copyright © 2016 John Wiley & Sons, Ltd.     

粉防己碱与可乐定对小鼠和大鼠吗啡躯体依赖的影响

目的:观察粉防己碱(Tet)与可乐定对吗啡依赖小鼠和大鼠催促戒断症状的影响。方法:采用剂量递增方式皮下注射酸吗啡,建立吗啡依赖小鼠和大鼠模型,用纳洛酮催瘾。结果:Tet 15,30或60 mg/kg,可明显抑制小鼠催促戒断后的体重下降及一些戒断体征,大鼠给予 Tet 15,30或60 mg/kg 预处理,可抑制1 h 体重下降,明显改善戒断时的行为表现,戒断症状评分随剂量增加而下降。Tet 15 mg/kg 与可乐定0.075 mg/kg 联用,对吗啡依赖小鼠和大鼠催促戒断症状有明显对抗作用。但以上处理对小鼠和大鼠的跳跃反应均无影响。结论:Tet 可缓解吗啡依赖小鼠和大鼠的戒断症状,小剂量 Tet 与可乐定联用可能是一种较好的用药方案。     

Yiguanjian cataplasm attenuates opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome

OBJECTIVE:To investigate the effect of Yiguanjian(YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome.METHODS:One hundred Swiss albino mice,of equal male to female ratio,were randomly and equally divided into 10 groups.A portion(3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment.Morphine(5 mg/kg) was intraperitoneally administered twice daily for 5days.YGJ cataplasm was prepared and pasted on the bare region of the mice immediately beforemorphine administration on day 3 and subsequently removed at the end day 5.On day 6,naloxone(8mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome.Behavioral observation was performed in two 30-min phases immediately after naloxone injection.RESULTS:The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone-induced experimental opioid withdrawal,in terms of withdrawal severity score and the frequencies of jumping,rearing,forepaw licking,and circling behaviors.However,YGJ cataplasm treatment did not alter the acute analgesic effect of morphine.CONCLUSION:YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms.Therefore,YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.     

Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer's disease model

Ethnopharmacological relevance

Bacopa monnieri (L.) Wettst., a plant belonging to the family Scrophulariaceae, has been used in the traditional system of Ayurvedic medicine to improve intelligence and memory for a long time. Therefore, the potential of this plant to protect against Alzheimer's disease has been raised but less supported document is available.

Aim of the study

To determine the effect of alcoholic extract of Bacopa monnieri on cognitive function and neurodegeneration in animal model of Alzheimer's disease induced by ethylcholine aziridinium ion (AF64A).

Materials and methods

Male Wistar rats were orally given the alcoholic extract of Bacopa monnieri at doses of 20, 40 and 80 mg/kg BW via feeding needle for a period of 2 weeks before and 1 week after the intracerebroventricular administration of AF64A bilaterally. Rats were tested for spatial memory using Morris water maze test and the density of neurons and cholinergic neurons was determined using histological techniques 7 days after AF64A administration.

Results

Bacopa monnieri extract improved the escape latency time (p < .01) in Morris water maze test. Moreover, the reduction of neurons and cholinergic neuron densities were also mitigated.

Conclusion

These findings suggest that Bacopa monnieri is a potential cognitive enhancer and neuroprotectant against Alzheimer's disease.     

Effect of Linalool on Morphine Tolerance and Dependence in Mice

Linalool, a terpene alcohol, has been shown to interact with the opioid system and N‐methyl‐ d ‐aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and100 mg/kg), clonidine (positive control), alpha‐2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail‐flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. Copyright © 2012 John Wiley & Sons, Ltd.     

Bacopa monnieri Increases Cerebral Blood Flow in Rat Independent of Blood Pressure

Bacopa monnieri (L.) Wettst. (Brahmi in India and Thailand) is an ayurvedic dementia treatment, but its effect on cerebral blood flow (CBF) is still unknown. We sought to test its chronic and acute effects on CBF compared with Ginkgo biloba and donepezil. CBF was measured by laser Doppler from rat cerebral cortex after 8 weeks of daily oral dosing of these drugs. Systolic blood pressure was also measured using the tail cuff method or via arterial cannulation. In rats treated with B. monnieri (40 mg/kg), CBF was 25% increased [2927 ± 123 perfusion units, (PU)] compared with shams (2337 ± 217 PU, p < 0.05, nine rats). G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20–60 mg/kg) had marked dose‐dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%. Likewise, CBF fell slightly with acute intravenous sodium nitroprusside and rose with noradrenaline. Donepezil (1 mg/kg) was slightly hypotensive without affecting CBF. Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile. Copyright © 2012 John Wiley & Sons, Ltd.     

Bacopa monnieri as augmentation therapy in the treatment of anhedonia,preclinical and clinical evaluation

Bacopa monnieri (L.) is widely used in Ayurvedic medicine as a neural tonic for improving intelligence and memory. Several studies highlighted its efficacy in neuropsychiatric diseases but there is no evidence regarding anhedonia. Aim of the present work was to preclinically and clinically test against anhedonia a standardized B. monnieri extract (20% bacosides). In a mouse model of a depressive‐like syndrome induced by lipopolysaccharide (LPS), the daily administration of the extract (50–200 mg kg^?1, p.o.) for 1 week, dose‐dependently counteracted the immobility time in Porsolt and Tail suspension tests (p < .01). At the sucrose preference test (directly related to the ability for feeling pleasure) the extract treatment (100 and 200 mg kg^?1) counteracted the reduction of sucrose intake induced by LPS (p < .01). Moreover, B. monnieri significantly reduced cytokines, cortisol, and artemin LPS‐dependent alterations in plasma while increased the brain‐derived neurotrophic factor levels (p < .05). The efficacy of the same extract was tested in a clinical study in which 42 patients with significant degree of anhedonia (evaluated as Snaith‐Hamilton Pleasure Scale [SHAPS] score ≥ 3) were enrolled. Patients were divided into two groups and treated with citalopram or citalopram associated with B. monnieri (300 mg bid) for 4 weeks. The Pears Sample T‐test showed a significant improvement (p < .05) in relevant scales (Hamilton depression rating scale, SHAPS, and strength and difficulties questionnaire) in the extract‐treated group in comparison to citalopram alone was recorded. These data suggest that B. monnieri extract may be effective for the management of anhedonia and therefore should be considered for future controlled trials.     

An Acute,Double‐Blind,Placebo‐Controlled Crossover Study of 320 mg and 640 mg Doses of a Special Extract of Bacopa monnieri (CDRI 08) on Sustained Cognitive Performance

Standardized extracts of the traditional Ayurvedic medicine Bacopa monnieri (BM) (Brahmi) have been recently shown to have cognitive enhancing effects in chronic administration studies. Pre‐clinical work has also identified a number of acute anxiolytic, nootropic, and cardiovascular effects of BM. There has, however, been little research on the acute effects of BM on cognitive function. The current study aimed to assess the acute effects of a specific extract of BM (KeenMind® ‐ CDRI 08) in a double‐blind, placebo‐controlled study in normal healthy participants who completed a cognitively demanding series of tests. Twenty‐four healthy volunteers completed six repetitions of the Cognitive Demand Battery (CDB) after consuming a placebo, 320 mg BM or 640 mg of BM in a cross‐over design and provided cardiovascular and mood assessments before and after treatment. Change from baseline scores indicated that the 320 mg dose of BM improved performance at the first, second, and fourth repetition post‐dosing on the CDB, and the treatments had no effect upon cardiovascular activity or in attenuating task‐induced ratings of stress and fatigue. It was concluded that assessment of an earlier pharmacological window and use of less memory‐specific cognitive tests together with more temporally sensitive measures of brain activity may improve our understanding of the acute neurocognitive properties of BM. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of Jitai Tablet,A Traditional Chinese Medicine,on Spontaneous Withdrawal Symptoms and Modulation of Dopaminergic Functions in Morphine‐Dependent Rats

Chronic opioid abuse can cause damage to dopamine neurons. However, there are currently no effective pharmacotherapies to reverse this damage, even though progress has been made in the development of therapeutic strategies for opioid dependence. The Jitai tablet (JTT) is a traditional Chinese medicine formulation most commonly used for opioid addiction treatment in China. In a morphine spontaneous withdrawal rat model we investigated the effects of JTT, either given before (pre‐treatment) or after (post‐treatment) morphine administration, on the dopamine system. Our study has shown the following: (1) pre‐ and post‐treatment with JTT were effective at alleviating the wet dog shakes and episodes of writhing; (2) pre‐treatment with JTT inhibited the morphine‐induced decreases in dopamine transporter (DAT), dopamine D₂ receptor (D₂R) and tyrosine hydroxylase (TH) levels in the striatum (p < 0.01, compared with morphine group) and maintained them at normal levels; and (3) post‐treatment with JTT restored the densities of DAT, D₂R and TH in the striatum to normal levels (p < 0.01, compared with morphine group). These results support the notion that modulation of the dopamine system in the striatum may play a role for JTT's therapeutic effect on the alleviation of opioid withdrawal symptoms. Copyright © 2015 John Wiley & Sons, Ltd.     

Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: Effect of Bacopa monnieri and bacoside-A

Aim of the study

Gamma-aminobutyric acid A receptors are the principal mediators of synaptic inhibition in striatal neurons and play an important role in preventing the spreading of seizures through the striatum. In the present study, effect of Bacopa monnieri (L.) Pennel and its active component bacoside-A on spatial recognition memory deficit and alterations of GABA receptor in the striatum of epileptic rats were investigated.

Materials and methods

Total GABA and GABA_A receptor numbers in the control and epileptic rats were evaluated using [³H]GABA and [³H]bicuculline binding. GABA_Aα1, GABA_Aα5, GABA_Aγ3 and GABA_Aδ gene expressions were studied. Behavioral performance was assed using Y-maze.

Results

Scatchard analysis of [³H]GABA and [³H]bicuculline in the striatum of epileptic rats showed significant decrease in B_max compared to control. Real-Time PCR amplification of GABA_A receptor subunits such as GABA_Aα1, GABA_Aα5 and GABA_Aδ, were down regulated (p < 0.001) in the striatum of epileptic rats compared to control. Epileptic rats have deficit in Y-maze performance. Bacopa monnieri and bacoside-A treatment reversed these changes to near control.

Conclusion

Our results suggest that decreased GABA receptors in the striatum have an important role in epilepsy associated motor learning deficits and Bacopa monnieri and bacoside-A has a beneficial effect in the management of epilepsy.     

Effect of crocin on the morphine‐induced antinociception in the formalin test in rats

In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra‐plantar (i.pl.) injection of formalin (50 μL, 1%), and the time spent licking and biting of the injected paw was measured for 1 h. Formalin induced a marked biphasic (first phase: 0–5 min and second phase: 15–45 min) pain response. Morphine (1 mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2 mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2 mg/kg) significantly (p < 0.05) prevented morphine (1 mg/kg)‐induced antinociception. Crocin at doses of 50, 100 and 200 mg/kg significantly (p < 0.05) attenuated pain. Crocin (100 mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1 mg/kg, s.c.)‐induced antinociception. Naloxone (2 mg/kg) did not reverse the suppressive effect of crocin (100 mg/kg) on pain. Crocin at a dose of 400 mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone‐sensitive mechanism produced analgesia. Crocin produced a dose‐dependent antinociceptive effect. In addition, crocin increased morphine‐induced antinociception, but naloxone did not change the antinociceptive effect of crocin. Copyright © 2009 John Wiley & Sons, Ltd.     

Hypnotic, anticonvulsant and muscle relaxant effects of Rubus brasiliensis. Involvement of GABAA-system

Rubus brasiliensis hexanic fraction induced anxiolysis in rodents, which was reversed by flumazenil, a specific GABA_A-benzodiazepine receptor antagonist (Nogueira and Nogueira). Then, we investigated if this hexanic fraction was able to induce hypnotic, anticonvulsant and muscle relaxant effects, and the involvement of GABA_A-system. The hexanic fraction (50, 100, 150 and 300 mg/kg, vo) was administered to male Swiss mice, 30 min before the tests. Only the dose of 300 mg/kg of this fraction decreased the latency and increased sleeping time in the barbituric-hypnosis test (sodium pentobarbital, 30 mg/kg, ip), prevented the pentylenetetrazol seizures (70 mg/kg, ip) and induced muscle relaxant (inclined plane) in 100% of animals. These effects were reversed by flumazenil (3 mg/kg, ip). In conclusion: (1) R. brasiliensis hexanic fraction induced hypnotic, anticonvulsant and muscle relaxant effects, in mice, and the GABA_A–benzodiazepine receptor may play an important role in the effects of this fraction; (2) it is strongly suggested that this fraction contains a benzodiazepine-like principle.     

Effect of Curcumin Against Pentylenetetrazol‐Induced Seizure Threshold in Mice: Possible Involvement of Adenosine A1 Receptors

Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20–120 mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80 mg/kg) was prevented by 8‐phenyltheophylline (0.5 mg/kg, i.p., non‐selective adenosine receptor antagonist) and 8‐cyclopentyl‐1,3‐dipropylxanthine (5 mg/kg, i.p., adenosine A₁ receptor antagonist) but not by 8‐(3‐cholorostryl)caffeine (4 mg/kg, i.p., adenosine A_2A receptor antagonist). Further, 5′‐N‐ethylcarboxamidoadenosine (0.005 mg/kg, i.p., non‐selective A₁/A₂ receptor agonist), or N⁶‐cyclohexyladenosine (0.2 mg/kg, i.p., adenosine A₁ receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5′‐(N‐cyclopropyl) carboxamidoadenosine (0.1 mg/kg, i.p., adenosine A_2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A₁ but not A_2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions. Copyright © 2013 John Wiley & Sons, Ltd.     

针灸"肾俞"穴对吗啡依赖大鼠戒断反应和成瘾脑区神经元活动的影响

目的:探讨电针肾俞穴对吗啡戒断的影响及其作用机制.方法:建立急性吗啡成瘾模型,采用瞬时基因c-fos表达作为神经元活动的标志,运用免疫组化技术,对电针"肾俞"穴对抗吗啡戒断症状以及可能涉及的脑区进行研究.结果:电针"肾俞"穴能明显抑制大鼠戒断症状,降低导水管周围灰质区、下丘脑室旁核、海马CA1区、CA3区和齿状回和下丘脑外侧区的c-fos表达,但增加杏仁基底外侧核、杏仁中央核和伏隔核核区(core)的c-fos表达.结论:电针"肾俞"穴能有效抑制吗啡戒断症状,电针对抗阿片类药物依赖涉及多个中枢核团.     

丹参提取物对小鼠吗啡身体依赖性形成的影响及其机制

目的观察丹参提取物(含隐丹参酮85.11%)对小鼠吗啡身体依赖性形成及其对脑内环磷酸腺苷(cAMP)和一氧化氮(NO)生成的影响。方法剂量递增sc吗啡建立小鼠吗啡依赖模型,观察丹参提取物对盐酸纳洛酮催促吗啡依赖小鼠戒断症状的影响,并分别用放射免疫分析法、硝酸还原酶法测定小鼠脑内cAMP和NO水平。结果丹参提取物(80 mg/kg)可显著降低吗啡依赖小鼠催促戒断症状;对吗啡依赖小鼠脑内cAMP无明显影响,但可显著降低吗啡依赖小鼠脑内NO水平。结论丹参提取物能缓解吗啡依赖小鼠的戒断症状,其机制可能与下调脑内NO水平有关。     

青风藤及青藤碱对吗啡依赖小鼠位置偏爱效应及脑内组胺水平的影响

目的:探讨青风藤及其有效成分青藤碱对吗啡诱导的小鼠条件性位置偏爱(CPP)及脑内组胺(HA)水平的影响。方法:连续给予吗啡(9mg/kg,sc)6d,引起小鼠产生显著的条件性位置偏爱效应。在位置偏爱训练的第4天开始每天sc吗啡前45min分别给予青风藤醇提液(10g/kg,ig)、青藤碱(60mg/kg,im)、苯海拉明组(30mg/kg,ip)、CP48/80组(5mg/kg,sc)或L组氨酸组(750mg/kg,ip),连续给药3天。用荧光分光光度法测定脑内组胺含量。同时检测对小鼠的奖赏效应或厌恶效应。结果:吗啡模型组小鼠在伴药箱中停留的时间明显延长,小鼠脑内HA水平显著升高。青风藤或青藤碱可显著抑制吗啡引起的小鼠位置偏爱的形成,降低脑内的HA含量。青风藤、青藤碱及L组氮酸对正常小鼠脑内组脑水平有升高作用,但三药本身并不使小鼠产生奖赏或厌恶效应。CP48/80对正常及吗啡依赖小鼠脑内组胺含均有明显减少作用,但该药对CPP无明显影响。结论:吗啡诱导的小鼠位置偏爱效应与脑内HA水平升高、中枢组胺能神经系统激活有关。青风藤及青藤碱能消除吗啡诱导的小鼠条件性位置偏爱的形成,对脑内组胺水平的改变具有调节作用。     

Central Nervous System Activities of Hypericum origanifolium Extract via GABAergic and Opioidergic Mechanisms

Pharmacological effects of hydroalcoholic extract prepared from Hypericum origanifolium Willd. (Guttiferae) on behavioral parameters and pain perceptions of mice were investigated in this study. Depression, anxiety, spontaneous locomotor activity, and motor coordination parameters of mice were assessed by modified forced swimming, hole board, activity cage, and rota‐rod tests, respectively. In addition, antinociceptive effect was evaluated by performing hot‐plate, tail‐clip, and formalin tests. Reboxetine (20 mg/kg), diazepam (1 mg/kg), and morphine (10 mg/kg) were used as reference antidepressant, anxiolytic, and analgesic drugs, respectively. Phytochemical analyses exhibited that chlorogenic acid (2317.12 ppm) and rutin (2108.79 ppm) were the main phenolic compounds in the H. origanifolium extract. The extract (50, 100, and 250 mg/kg) induced significant antidepressant, anxiolytic, and antinociceptive activities following the acute administrations. Anxiolytic effect was antagonized by flumazenil (a benzodiazepine receptor antagonist, 2.5 mg/kg, i.p.) pre‐treatment, which indicated the participation of GABA(A)‐benzodiazepine receptor complex in the activity. Moreover, centrally and peripherally mediated antinociception reversed by naloxone (a non‐selective opioid receptor antagonist, 5 mg/kg, i.p.) pre‐treatment, indicating the involvement of opioid system in the pharmacological action. These findings are the first to indicate the pharmacological effects of the H. origanifolium extract on the emotional state and pain perceptions of mice. Copyright © 2012 John Wiley & Sons, Ltd.