Effect of Indian Hypericum perforatum Linn on animal models of cognitive dysfunction

The effect of a standardised 50% ethanolic extract of Indian Hypericum perforatum (IHp) was investigated for its putative nootropic activity on various experimental paradigms of learning and memory, viz. transfer latency (TL) on elevated plus-maze, passive avoidance (PA), active avoidance (AA), scopolamine and sodium nitrite induced amnesia (SIA & NIA) in albino rats. Pilot studies indicated that single dose administration of IHp had little or no acute behavioural effects, hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.), once in daily for three consecutive days, while piracetam (500/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard drug. Control rats were treated with equal volume of vehicle (0.3% carboxymethyl cellulose (CMC)). IHp and piracetam when given alone shortened the TL on day 1, 2, 9 and also antagonised the amnesic effects of scopolamine and sodium nitrite on the TL significantly. IHp had no significant per se effect on the retention of the PA in rats. Only the higher dose (200 mg/kg, p.o.) produced a significant reversal of scopolamine induced PA retention deficit but no significant reversal was observed with sodium nitrite. Piracetam showed significant per se facilitatory effect on PA retention and also reversed the scopolamine and sodium nitrite induced impaired PA retention. In the AA test, IHp in both the doses, and piracetam, facilitated the acquisition and retention of AA in rats and the IHp effects were found to be dose dependent. Both the doses of IHp and piracetam significantly attenuated the scopolamine and sodium nitrite induced impaired retention of AA. These results indicate a possible nootropic action of IHp, which was qualitatively comparable with that induced by piracetam.     

Effects of red ginseng saponins and nootropic drugs on impaired acquisition of ethanol-treated rats in passive avoidance performance

Effects of single and repeated administration of red ginseng total saponins (ROTS) and nootropic drugs were examined on impairment of acquisition induced by single oral administration of 3 g/kg ethanol (EtOH) in a step through test. The inhibitory effect of EtOH on acquisition was significantly reduced following single or repeated RGTS administration. The nootropic drugs, piracetam and N-methyl-D-glucamine, given orally significantly reduced impairment of acquisition induced by EtOH. On the other hand, the inhibitory effect of repeated RGTS on the EtOH-induced amnesia was blocked by the pretreatment of alpha-methyl-p-tyrosine (alpha-MT), an inhibitor of catecholamine synthesis, in a dose-dependent manner but not p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, whereas the inhibitory effect of repeated N-methyl-D-glucamine on the EtOH-induced amnesia was blocked neither by alpha-MT nor PCPA. These results suggest that repeated RGTS and N-methyl-D-glucamine ameliorate the impairing effect of EtOH on acquisition, and the effect of RGTS on EtOH-induced amnesia is dependent on the catecholaminergic but not serotonergic neuronal activity, while RGTS and N-methyl-D-glucamine seem to have a different mechanism on EtOH-induced amnesia.     

Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice

Ashwagandha (Withania somnifera L.) root extract (50, 100 and 200 mg/kg; orally) improved retention of a passive avoidance task in a step-down paradigm in mice. Ashwagandha (50, 100 and 200 mg/kg; orally) also reversed the scopolamine (0.3 mg/kg)-induced disruption of acquisition and retention and attenuated the amnesia produced by acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic treatment with ECS, for 6 successive days at 24 h intervals, disrupted memory consolidation on day 7. Daily administration of ashwagandha for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. Ashwagandha, administered on day 7, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On the elevated plus-maze, ashwagandha reversed the scopolamine (0.3 mg/kg)-induced delay in transfer latency on day 1. On the basis of these findings, it is suggested that ashwagandha exhibits a nootropic-like effect in naive and amnesic mice.     

Neuropharmacological profile of Eclipta alba (Linn.) Hassk

The present study deals with the investigation of standardized and phytochemically evaluated aqueous and hydroalcoholic extracts of the plant Eclipta alba for sedative, muscle-relaxant, anxiolytic, nootropic and anti-stress activities. The hydrolyzed fraction of the aqueous extract was also subjected to similar studies in rats. The aqueous and hydroalcoholic extracts were administered in a dose of 150 and 300 mg/kg, p.o., while the hydrolyzed fraction was administered in a dose of 30 mg/kg, p.o. The findings indicated nootropic activity of the aqueous extract (300 mg/kg, p.o.) and its hydrolyzed fraction (30 mg/kg, p.o.). The effect of the extracts on stress-induced alterations was evaluated. The aqueous extract and the hydrolyzed fraction provided protection against cold restraint induced gastric ulcer formation and also normalized the white blood cell count in the milk induced leukocytosis challenge model. The hydroalcoholic extract on the other hand demonstrated a significant effect only in the milk induced leukocytosis challenge model. The results point towards the potential neuropharmacological activity of the plant Eclipta alba as a nootropic and also having the property of attenuating stress induced alterations. Further neurochemical investigations can unravel the mechanism of action of the plant drug with respect to nootropic activity and help to establish the plant in the armamentarium of nootropic agents.     

Neuropharmacological evaluation of Ginkgo biloba phytosomes in rodents

On oral administration, Ginkgo biloba phytosomes significantly reduced pentobarbitone-induced sleeping time, produced an alteration in the general behaviour pattern, increased spontaneous motility and inhibited the chlorpromazine-induced blockade of conditioned and unconditioned responses in rodents. They exhibited both antiamnestic and antidepressant activities in the scopolamine-induced amnesia test and behavioural despair test, respectively. However, the phytosomes failed to show anticonvulsant activity. The observations suggest that the G. biloba phytosomes possess moderate antiamnestic/nootropic activity.     

基于内源性大麻素系统的抑郁症发病机制及其在中药研究中的应用

抑郁症是一种难以调控的疾病,目前缺乏高效、稳定且安全的抗抑郁药,寻找抑郁症发病新机制对抗抑郁药物的研发具有重要意义。近年来,研究发现抑郁症与内源性大麻素系统(endocannabinoid system,ECS)的紊乱密切相关,然而涉及的机制较为复杂,亟待整理。当下,通过ECS的调控来治疗抑郁症是一种新途径,而中药在该途径上存在天然优势,从中开发抗抑郁新药具有广泛的研究前景。鉴于此,对ECS与抑郁症的关系及中药介导ECS发挥抗抑郁作用的潜力进行了分析,以期为抑郁症发病机制的研究提供参考,为抗抑郁药物的研发提供新策略。     

Effect of Evolvulus alsinoides Linn. on learning behavior and memory enhancement activity in rodents

In the Ayurvedic system of medicine, the whole herb of ‘Shankhpushpi’ has been employed clinically for centuries for its memory potentiating, anxiolytic and tranquilizing properties. The present study was undertaken to investigate the effects of Evolvulus alsinoides (EA), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's pole climbing apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanol extract of EA and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg/kg p.o.) of the ethanol extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both doses of all the extracts of EA significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg/kg i.p.). Nootropic activity was compared using piracetam as the standard. EA also exhibited potent memory enhancing effects in the step‐down and shuttle‐box avoidance paradigms. Copyright © 2009 John Wiley & Sons, Ltd.     

An Acute,Double‐Blind,Placebo‐Controlled Cross‐over Study of 320 mg and 640 mg Doses of Bacopa monnieri (CDRI 08) on Multitasking Stress Reactivity and Mood

Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive‐enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co‐occur in humans. The current double‐blind, placebo‐controlled cross‐over study assessed the acute effects of a specific extract of BM (KeenMind® ‐ CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7‐day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853). Copyright © 2013 John Wiley & Sons, Ltd.     

Enhanced conditioned inhibitory avoidance by a combined extract of Zingiber officinale and Ginkgo biloba

Previous work has shown that intragastric administration of Zingicomb, a preparation consisting of Zingiber officinale and Ginkgo biloba extracts, has anxiolytic-like properties. The aim of the present study was to assess the effects of acute treatment with this preparation on inhibitory avoidance learning. The influence of pre-trial administered Zingicomb (ZC) on inhibitory avoidance conditioning was investigated in adult male Wistar rats, with a one-trial step-through avoidance task. The animals were treated intragastrically with either vehicle, 0.5, 1, 10 or 100 mg/kg ZC 60 min prior to the acquisition trial. When tested 24 h after training, rats which had received 10 mg/kg ZC exhibited significantly longer step-through latencies than vehicle treated animals. This result, thus, demonstrates the beneficial effects of Zingicomb on conditioned inhibitory avoidance. Unlike conventional anxiolytic drugs, such as the benzodiazepines, which tend to have amnesic properties, this phytopharmacon is a potent anxiolytic agent which, additionally, can facilitate performance on a learning task, indicating promising clinical applications.     

Nootropic activity of Albizzia lebbeck in mice

The effect of saponin containing n-butanolic fraction (BF) extracted from dried leaves of Albizzia lebbeck on learning and memory was studied in albino mice using passive shock avoidance paradigm and the elevated plus maze. Significant improvement was observed in the retention ability of the normal and amnesic mice as compared to their respective controls. We have also studied the effects of BF on the behavior influenced by serotonin (5-HT), noradrenaline and dopamine. The brain levels of serotonin, gamma-aminobutyric acid (GABA) and dopamine were also estimated to correlate the behavior with neurotransmitter levels. The brain concentrations of GABA and dopamine were decreased, whereas the 5-HT level was increased. The data indicate the involvement of monoamine neurotransmitters in the nootropic action of BF of A. lebbeck.     

Neurophysiological effects of an extract of Eschscholzia californica Cham. (Papaveraceae)

An aqueous alcohol extract of Eschscholzia californica (Ec) has been evaluated for benzodiazepine, neuroleptic, antidepressant, antihistaminic and analgesic properties, in order to complete the study of the sedative and anxiolytic effects previously demonstrated. The plant extract did not protect mice against the convulsant effects of pentylenetetrazol, and did not cause muscle relaxant effects but appeared to possess an affinity for the benzodiazepine receptor: thus, flumazenil, an antagonist of these receptors, suppressed the sedative and anxiolytic effects of the extract. The Ec extract induced peripheral analgesic effects in mice but did not possess antidepressant, neuroleptic or antihistaminic effects.     

Effects of Methyl and Isopropyl N‐methylanthranilates from Choisya ternata Kunth (Rutaceae) on Experimental Anxiety and Depression in Mice

Choisya ternata Kunth (Rutaceae) is a plant species used in Mexican folk medicine for its antispasmodic and simulative properties. Recently, we identified a new alkaloid, isopropyl N‐methylanthranilate, and a related one, methyl N‐methylanthranilate, from the essential oil of this species and have proven them to possess antinociceptive activity even at 0.3 mg/kg. In the present study, anxiolytic and antidepressant effects of the two compounds have been studied in open field, horizontal wire, light/dark, forced swimming and tail suspension tests, as well as the effect on the onset and duration of diazepam‐induced sleep in BALB/c mice. The volatile alkaloids (50–200 mg/kg, administered intraperitoneally), without having a muscle relaxant effect, caused a significant increase in the time the animals spent in an unsecured and putatively dangerous area when compared with the control group but had no effect on the number of crossings between the light/dark compartments. In addition to this anxiolytic activity, a significantly antidepressant‐like effect was apparent at all tested doses, which was not due to an increase in locomotive activity. The anthranilates administered on their own did not induce sleep in mice but significantly prolonged the diazepam‐induced sleep, in a dose‐dependent way, suggesting an interaction with the gamma‐aminobutyric acid receptor complex. Copyright © 2012 John Wiley & Sons, Ltd.     

Anxiolytic and antidepressant activities of Pelargonium roseum essential oil on Swiss albino mice: Possible involvement of serotonergic transmission

The anxiolytic and antidepressant activities of the Reunion Geranium (Pelargonium roseum Willd) essential oil (EO) were evaluated in male Swiss albino mice by intraperitoneal administration of 10, 20, and 50 mg/kg bw using elevated plus maze (EPM), open‐field test (OFT), and forced swimming test (FST). Moreover, we evaluated whether the 5‐HT_1A and GABA_A–benzodiazepine receptor systems are involved in the anxiolytic effects through the coadministration of WAY‐100635 (a selective 5‐HT_1A receptor antagonist) and flumazenil (an antagonist of benzodiazepine). GC–MS revealed the monoterpene alcohols citronellol (35.9%) and geraniol (18.5%) as the main components of the P. roseum EO. EO was effective in increasing the total number of entries and time spent in the open arms of EPM whereas number of rearing in OFT was significantly decreased in comparison with the control. In the FST, immobility time decreased in EO treated mice. Pretreatment with WAY‐100635, but not Flumazenil, was able to reverse the effects of the EO in the EPM and FST, indicating that the EO activity occurs via the serotonergic but not GABAergic transmission. Overall, results of this work showed significant anxiolytic and antidepressant activity of P. roseum EO and confirmed the traditional uses of Pelargonium species as calming agents.     

Differentiation of acupuncture and nonacupuncture points by difference of associated opioids in the spinal cord in production of analgesia by acupuncture and nonacupuncture point stimulation, and relations between sodium and those opioids

Antiserum of methionine-enkephalin (Met-Enk) applied intrathecally abolished acupuncture analgesia (AA) caused by low frequency stimulation of an acupuncture point (tibial muscle, APS) of rats, but antisera of leucine-enkephalin (Leu-Enk) and dynorphin (Dyn) did not. Antiserum of Dyn applied intrathecally abolished analgesia (NAA) produced by stimulation of a nonacupuncture point (NAPS) which was revealed by lesion in the analgesia inhibitory system (AIS), whereas antisera of Met-Enk and Leu-Enk did not. NAA was antagonized by the kappa-receptor antagonist, Mr2266, and analgesia was produced by the kappa-agonist, U50-488H, in the AIS lesioned rats. Potentials in the dorsal periaqueductal central gray (D-PAG) evoked by APS were antagonized by naloxone and antiserum of Met-Enk, and those in the lateral PAG (L-PAG) evoked by NAPS were antagonized by Mr2266 and antiserum of Dyn. After adrenalectomy, AA, potentials in the D-PAG, and analgesia caused by stimulation (SPA) of the D-PAG were abolished 12 hour; and NAA, potentials in the L-PAG, and SPA of the L-PAG were abolished in 24 hour. All were then restored one hour after intravenous application of 1 ml of 5% NaCl solution. AA and NAA which were augmented for several hours before their abolition after adrenalectomy were not antagonized by naloxone nor M 2266, respectively. However naloxone and Mr2266 did antagonize AA and NAA, respectively, one hour after treatment with 1 ml of 5% NaCl solution.     

Effects of Hypericum perforatum extract on diabetes‐induced learning and memory impairment in rats

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin‐induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients. Copyright © 2010 John Wiley & Sons, Ltd.     

柠檬醛对大鼠及人血小板聚集作用的影响

柠檬醛是山鸡椒的有效成份之一。研究结果表明:Citral对ADP-Collagen诱导的大鼠血大板聚集有明显的抑制作用(P <0.01),对AA诱导的人外周血血小板聚集也有明显的抑制作用。大鼠口服1g/kg citral也能抑制由AA诱导的血小板聚集。另外,Citral还能抑制血小板聚集时产生的TxA_2样物质的释放。     

Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant

Many epileptic patients suffer from cognitive impairments; both the underlying pathology and antiepileptic drug therapy can cause such deficits. Phenytoin, one of the widely used anticonvulsants, is known to adversely affect cognitive function. A reputed Indian nootropic plant Bacopa monniera (BM) was evaluated alone and in combination with phenytoin for its effect on (a) passive-avoidance (PA) task; (b) maximal electroshock seizures; and (c) locomotor activity in mice. Phenytoin (PHT, 25 mg/kg po x 14 days) adversely affected cognitive function in the PA task. BM extract (40 mg/kg x 7 days), given along with phenytoin in the second week of the two-week regimen, significantly reversed PHT-induced impairment. Both acquisition and retention of memory showed improvement without affecting its anticonvulsant activity. The observed cognitive effects of PHT and BM were found to be independent of motor stimulation. The results provide evidence for potential corrective effect of BM in cognitive deficit associated with PHT therapy.     

Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats

Aim of the Study

Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats.

Materials and Methods

4-5 weeks Spraque-Dawley rats were administered with concentration 1, 3, 5, 10, 30 mg/kg of A-A, baclofen, scopolamine and saline intra peritoneally and were evaluated for passive avoidance (PA), active avoidance (AA) and changes in blood pressure (BP).

Results

Treatment 30 mg/kg of A-A resulted in significantly dose-dependently improved memory, with increased retention latency to enter difference compartment in PA test compared to baclofen, saline and scopolamine. Furthermore, 30 mg/kg of A-A was significantly higher on learning abilities on 1st day but there was no significantly difference on avoidance memory ability after 7 days of retention. Low reading in blood pressure dose-dependent significantly difference was observed in the 30 mg/kg of A-A group compared to saline group.

Conclusions

Administration A-A facilitated PA and AA on memory and learning and but had no effect on active avoidance on memory. Hence, may serve useful memory and learning with less effect in blood pressure in promoting memory and learning increases.     

Immune Tolerance Effect in Mesenteric Lymph Node Lymphocytes of Geniposide on Adjuvant Arthritis Rats

Rheumatoid arthritis (RA) is a systemic, Th1 cytokine‐predominant autoimmune disease result in a chronic and inflammatory disorder. Geniposide (GE), an iridoid glycoside compound that is purified from Gardenia jasminoides Ellis, has antiinflammatory and other immunoregulatory effects, but its exact mechanism of actions on RA is unknown. The aim of this study was to elucidate antiinflammation effects of GE on adjuvant arthritis (AA) rats and its possible immune tolerance mechanisms. Male Sprague–Dawley rats were administered with GE (30, 60, and 120 mg/kg) orally from day 17 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Levels of interleukin‐2 (IL‐2), IL‐4, and transforming growth factor‐β1 were tested by ELISA. The expression of β2‐AR, GRK2, and β‐arrestin‐1 and β‐arrestin‐2 was detected by western blot. Geniposide was found to relieve the secondary hind paw swelling and arthritis scores, along with attenuating histopathologic changes and decreasing IL‐2 and increasing IL‐4, transforming growth factor‐β1 in mesenteric lymph node (MLN) lymphocytes of AA rats. In addition, GE in vivo increased the expression of β2‐AR and decreased the expression of GRK2, β‐arrestin‐1 and β‐arrestin‐2, and level of cyclic adenosine monophosphate of MLN lymphocytes in AA rats. From these results, we can infer that GE on immune tolerance effects, β2‐AR desensitization, and β2‐AR‐AC‐cyclic adenosine monophosphate transmembrane signal transduction of MLN lymphocytes plays crucial roles in antiinflammatory and immunoregulatory pathogeneses of RA. Copyright © 2017 John Wiley & Sons, Ltd.     

雷公藤多苷对大鼠佐剂性关节炎黏膜免疫的影响

目的观察雷公藤多苷对大鼠佐剂性关节炎(AA)黏膜免疫的影响。方法完全弗氏佐剂免疫大鼠,以雷公藤多苷治疗,观察大鼠黏膜免疫各项指标。结果雷公藤多苷可以改善AA大鼠病理改变,并调节AA大鼠的黏膜免疫功能。结论雷公藤多苷对AA模型大鼠有抗炎和免疫抑制作用。