Danshensu attenuates scopolamine and amyloid-ß-induced cognitive impairments through the activation of PKA-CREB signaling in mice.

Alzheimer's disease (AD) is an important chronic neurodegenerative disorder and is mainly associated with cognitive dysfunction. At present, bioactive compounds from traditional medicinal plants have received much attention for the enhancement of cognitive function. Danshensu, a phenolic acid isolated from herbal medicines, has various pharmacological activities in the central nervous system, including anxiolytic-like and neuroprotective properties. The present study aimed to investigate the ameliorating effects of danshensu on scopolamine- and amyloid-ß (Aß) protein-induced cognitive impairments in mice. Danshensu (3 and 10 mg/kg, p.o.) effectively ameliorated scopolamine-induced cognitive dysfunction in mice, as measured in passive avoidance and Y-maze tasks. In a mechanistic study, danshensu inhibited monoamine oxidase A (MAO-A) activity but not MAO-B. Additionally, danshensu treatment increased the dopamine level and the phosphorylation levels of protein kinase A (PKA) and cAMP response element binding protein (CREB), in the cortex of the brain. Furthermore, the ameliorating effect of danshensu against scopolamine-induced cognitive impairment was fully blocked by H89, a PKA inhibitor. Finally, danshensu also ameliorated Aß-induced cognitive impairments in an animal model of AD. The results revealed that danshensu treatment significantly improved scopolamine and Aß-induced cognitive impairments in mice by facilitation of dopamine signaling cascade such as PKA and CREB due to MAO-A inhibition. Thus, danshensu could be used as a promising therapeutic agent for preventing and treating AD.

Datura and Brugmansia plants related antimuscarinic toxicity: an analysis of poisoning cases reported to the Taiwan poison control center.

INTRODUCTION: Datura and Brugmansia plants, especially Datura species, have been used for their hallucinogenic effects in the United States and Europe; whereas Datura plants have been used as a traditional medicine in many Asian countries. This study was conducted to better understand the pattern and outcome of Datura/Brugmansia plant related poisoning in Taiwan. METHODS: This is a retrospective case series study of all cases with Datura/Brugmansia exposure reported to the Taiwan Poison Control Center between 1986 and 2015. Data for patients with relevant poisoning were reviewed and abstracted. Logistic regression analysis was used to identify potential predictors of the severity of poisoning; bivariate analysis was employed to assess the effectiveness of physostigmine in the treatment of Datura/Brugmansia poisoning. RESULTS: A total of 203 cases involving 114 Datura exposures and 89 Brugmansia suaveolens exposures were eligible for analysis. Using Datura/Brugmansia for a medicinal purpose by the patients without consulting Chinese medicine practitioners was the most common reason of poisoning (81.2%); whereas only 2% of the patients were poisoned after medicinal use associated with the prescription from Chinese medicine practitioners. None of the 203 patients had used Datura/Brugmansia plant for recreational purpose. Most frequently observed clinical effect was mydriasis (53.2%), followed by confusion (40%), tachycardia (35.5%), dry mouth (35.5%), dizziness (34%), dry skin (32.5%), and delirium (31%). Seventy-three cases (36%) had severe effects; none of them died. Misidentification of the plants and ingestion of plant parts other than flowers were positively associated with the severity of poisoning. Forty patients (19.7%) received physostigmine therapy and patients receiving physostigmine had an earlier resolution of central nervous system toxicity than those who did not. CONCLUSIONS: Medicinal use without consulting Chinese medicine practitioners is the main reason for Datura/Brugmansia poisoning in Taiwan. Consumption of parts other than flowers and misidentification of the plants predicted the severity of poisoning in this study. Patients who received physostigmine appear to have earlier improvement in the central nervous system effects. No adverse events were reported from physostigmine administration.

Effect of hydroalcoholic Echium amoenum extract on scopolamine-induced learning and memory impairment in rats.

CONTEXT: Scopolamine, a muscarinic receptor antagonist, causes memory loss that resembles Alzheimer's disease (AD). Echium amoenum L. (Boraginaceae) is a famous medicinal plant of Iran that is traditionally used as a sedative and mood enhancer. OBJECTIVE: This study evaluates the effect of hydroalcoholic extract of E. amoenum flowers on scopolamine-induced memory impairment in rats. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into five groups. Control group received normal saline, model group received scopolamine (0.7 mg/kg, IP, daily for 21 days), and test groups received E. amoenum extract (50, 75, and 100 mg/kg, IP, daily for 21 days) 30 min before each scopolamine injection. The elevated plus maze (EPM), shuttle box, novel object and rotarod tests were performed after treatment. Brain levels of malondialdehyde (MDA) and total antioxidant capacity (TCA) were also determined. RESULTS: Scopolamine-treated rats spent more time exploring the novel object compared to the control, and E. amoenum extract at all three doses significantly decreased the time spent exploring the novel object (p < 0.05). E. amoenum extract (75 and 100 mg/kg) significantly elongated the secondary latency in rats receiving scopolamine in the shuttle box test (p < 0.05). In addition, treatment with 75 and 100 mg/kg doses of E. amoenum extract significantly ameliorated scopolamine-induced motor in coordination in rotarod test (p < 0.05). It also significantly increased the time spent in the open arms and reduced the time spent in the closed arms of EPM (p < 0.05). Treatment of scopolamine-exposed rats with E. amoenum extract significantly increased TCA and reduced MDA level of brain (p < 0.05). DISCUSSION AND CONCLUSIONS: E. amoenum extract shows protective effect against scopolamine-induced impairment and is suggested to be tested in clinical trials to evaluate the efficacy on AD.

Sesame indicum, a nutritional supplement, elicits antiamnesic effect via cholinergic pathway in scopolamine intoxicated mice.

PURPOSE: Present study was undertaken to evaluate the antiamnesic effect of Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content) in scopolamine, a muscarinic antagonist intoxicated mice. METHODS: Male Swiss albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds (MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3 mg/kg, i.p.) was injected on day 14, 45 ± 10 min after MSSE administration. Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. To unravel the mechanism of action, we examined the effects of MSSE on the genes such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM1 ), and brain derived neurotrophic factor (BDNF) expression within hippocampus of experimental mice. Further, its effects on bax and bcl-2 were also evaluated. Histopathological examination of hippocampal CA1 region was performed using cresyl violet staining. RESULTS: MSSE treatment produced a significant and dose dependent increase in step down latency in passive avoidance test and decrease in transfer latency in elevated plus maze in scopolamine intoxicated injected mice. MSSE down-regulated AChE and mAChRM1 and up-regulated BDNF mRNA expression. Further, it significantly down-regulated the bax and caspase 3 and up-regulated bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE showed increased neuronal counts in hippocampal CA1 region when compared with scopolamine-vehicle treated mice. CONCLUSION: Sesame seeds have the ability to interact with cholinergic components involved in memory function/restoration and also an interesting candidate to be considered for future cognitive research. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016.

Cognitive enhancing effect of the fermented Gumiganghwal-tang on scopolamine-induced memory impairment in mice.

Gumiganghwal-tang (GT) is a traditional herbal medicine that is widely used for its anti-inflammatory, analgesic, and antipyretic actions. Fermented GT has been reported to inhibit acetylcholinesterase (AChE) activity and to exert a neuroprotective effect. In this study, we investigated the effect of fermented GT against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance tests. The results of the Morris water maze test indicated that fermented GT significantly decreased escape latency, as compared with that observed in the scopolamine-treated group. In the prove test, fermented GT attenuated the decreased time spent in the target quadrant observed after scopolamine treatment. The results of the passive avoidance test indicated that the treatment with fermented GT increased latency time when compared with the scopolamine-treated group. Moreover, fermented GT inhibited AChE activity in the hippocampi of the treated mice. These results suggest that fermented GT reduced scopolamine-induced amnesia in mice through AChE inhibition. Therefore, we hypothesize that fermented GT may be a useful therapeutic agent for the prevention or treatment of neurodegenerative diseases.

Antidiarrhoeal activity of aqueous leaf extract of Caladium bicolor (Araceae) and its possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Caladium bicolor (Araceae) is a horticulture plant also used by some traditional medicine practitioners in the treatment of diarrhoea and other gastrointestinal disorders. This study was conducted to evaluate the antidiarrhoeal activity of the aqueous leaf extract of C. bicolor and its possible mechanisms of action in rodents. MATERIALS AND METHODS: Normal and castor oil-induced intestinal transit and castor oil-induced diarrhoea tests were carried out in mice while gastric emptying and enteropooling tests were conducted in rats following the administration of distilled water (10 ml/kg, p.o.), C. bicolor extract (1-50mg/kg, p.o.) and loperamide (5mg/kg, p.o.). The probable mechanisms of action of C. bicolor was investigated following pre-treatment with yohimbine (10mg/kg, s.c.; α2-adrenoceptor antagonist), pilocarpine (1mg/kg, s.c.; non-selective muscarinic receptor agonist), prazosin (1mg/kg, s.c.; α1-adrenoceptor antagonist) and propranolol (1mg/kg, i.p.; non-selective ß-adrenoceptor antagonist) 15 min prior to administration of C. bicolor extract (50mg/kg, p.o.). After 30 min of pre-treatment with these drugs, the mice were subjected to the castor oil-induced intestinal transit test. RESULTS: C. bicolor extract did not produce significant (p>0.05) effect on normal intestinal transit unlike loperamide which caused significant (p<0.001) inhibition (61.57%). The extract caused significant (p<0.001) dose-dependent inhibition of castor oil-induced intestinal transit with peak effect, 100% inhibition, elicited at the dose of 50mg/kg compared to 86.97% inhibition for loperamide. Yohimbine and pilocarpine most significantly (p<0.001) reversed this effect of the extract. In the castor oil-induced diarrhoea test, the extract (1mg/kg) and loperamide significantly (p<0.05, 0.01) delayed the onset of diarrhoea. For diarrhoea score, the extract (1 and 50mg/kg) inhibited diarrhoea development (47.53% and 43.83% inhibition, respectively) like loperamide (5mg/kg; 54.94%). The in vivo antidiarrhoeal index of the extract at 1 and 50mg/kg was 50.07% and 42.81% respectively compared to 58.15% for loperamide. CONCLUSIONS: The results obtained in this study suggest that the aqueous leaf extract of C. bicolor possess antidiarrhoeal activity due to its anti-motility effect possibly via antagonist action on intestinal muscarinic receptors and agonist action on intestinal α2-adrenoceptors. This justifies the use of the extract in traditional medicine for the treatment of diarrhoea.

The effects of Zibu Piyin Recipe components on scopolamine-induced learning and memory impairment in the mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: The Zibu Piyin Recipe (ZBPYR) is derived from Zicheng Decoction, a traditional Chinese medicine formula recorded in the book of Bujuji, written by Wu Cheng in the Qing dynasty and used for clinical treatment of amnesia. Our aim was to study the effects of Zibu Piyin Recipe (ZBPYR) fractions on scopolamine-induced learning and memory impairment in the mouse. MATERIALS AND METHODS: Crude extracts were prepared using various solvents, and individual fractions produced following D101 macroporous resin column chromatography. The passive avoidance task, step down test and Morris water maze test were then performed in mice for the evaluation of learning and memory alterations. The effective fractions were then analyzed using GC-MS and polysaccharide measurement methods, respectively. RESULTS: The treatment group latency for the alcohol precipitation from water part (EP) and 95% ethanol part (95%E) following D101 macroporous resin column chromatography was significantly prolonged when compared to that of the scopolamine treated groups for both the passive avoidance task and step down test. In the Morris water maze tests, treatment with EP and 95%E resulted in a significantly shorter escape latency time (from the fourth day and the second day) and swimming distance (on the third day and from the third day) in scopolamine-induced mice. In the memory retention test, treatment with EP and 95%E dramatically shortened the latency to cross platform location and increased the numbers of platform location crosses in the scopolamine-induced mice. The polysaccharide content in EP was determined to be 69.79%. The 95%E was found to mainly contain asarone, α-cadinol, isocalamendiol, 2,4,7,14-tetramethyl-4-vinyl-tricyclo[5.4.3.0(1,8)]tetradecan-6-ol, 3-isopropyl-6,7-dimethyltricyclo[4.4.0.0(2,8)]decane-9,10-diol, 2-methyl-9-(prop-1- -en-3-ol-2-yl)-bicyclo[4.4.0]dec-2-ene-4-ol, diepicedrene-1-oxide, 7-methoxy-6-(3- -methyl-2-oxobutyl)-2H-1-benzopyran-2-one and diisooctyl phthalate when assessed using GC-MS analysis. CONCLUSION: These findings suggest that the polysaccharide and volatile oil present in ZBPYR exhibit ameliorating effects on scopolamine-induced memory dysfunction.

Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice.

Emblica officinalis, commonly known as amla, is an important medicinal plant of India. Its fruits have potent antioxidant activity due to the presence of tannoids, tannins, vitamin C and flavonoids. The aim of this study was to investigate the beneficial effect of the hydroalcoholic extract of the fruits of Emblica officinalis (EO) on memory impairment in Swiss albino mice. Scopolamine (1 mg kg(-1), i.p)was administered to induce amnesia and the memory was evaluated by using elevated plus-maze and passive avoidance tests. Piracetam (200 mg kg(-1), i.p.) was used as a standard nootropic agent. The EO extract was administered intraperitoneally in four graded doses (150, 300, 450 and 600 mg kg(-1)) for 7 consecutive days to different groups of mice. The mice were sacrificed on the 8th day following assessment of memory. The brain malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase (AchE)) activity was determined. It was observed that EO extract reversed the amnesia induced by scopolamine. The mean transfer latency and retention latency in the EO extract 600 mg kg(-1) group vs the vehicle treated scopolamine group was 13.46 sec (p<0.001) and 134.4 sec (p<0.001) vs 23.99 sec and 44.55 sec, respectively. EO extract treatment also significantly (p<0.001) ameliorated the oxidative stress induced by scopolamine administration. The mice brain MDA and GSH levels in the EO extract 600 mg kg(-1) group vs the scopolamine group were 29.95 nmol g(-1) of wet tissue and 51.87 microg g(-1) tissue vs 55.22 nmol g(-1) of wet tissue and 28.33 microg g(-1) tissue, respectively. Further, EO extract (300, 450 and 600 mg kg(-1), i.p) significantly (p<0.001) reversed the rise in brain acetyl cholinesterase (AchE) level induced by scopolamine. The mice brain Ach E levels in the EO extract 600 mg kg(-1) group as compared to the scopolamine group was 70.23 vs 151.49 U mg(-1) protein(-1), respectively. These results suggestthat EO possesses memory enhancing, antioxidant and anti-cholinesterase activity. It may be useful for the treament of cognitive impairments induced by cholinergic dysfunction. Its potential in the management of dementia and Azheimer disease needs to be further explored.

Improvement of pentylenetetrazol-induced learning deficits by valproic acid in the adult zebrafish.

Pentylenetetrazol (PTZ) has been shown to induce seizure-like behavior, learning deficits in passive avoidance response test, and an increase in hsp70 (heat shock protein 70) mRNA expression in the adult zebrafish; PTZ has been increasingly appreciated as an excellent model system for the study of seizures. In this study, we demonstrate that valproic acid (VPA), an antiepileptic drug, suppresses seizure-like behavior and improves learning ability in adult zebrafish treated with PTZ. Pretreatment with VPA significantly reduces rapid involuntary movement and abrupt changes in moving direction in the PTZ-treated zebrafish. PTZ-induced learning impairments were also improved in the zebrafish pretreated with 200 or 500 microM VPA. However, the scopolamine-induced impairments of learning ability were not improved by VPA pretreatment. It is worth noting that while the zebrafish treated with 500 microM VPA for 1-3 weeks learned the passive avoidance response, those treated with 1 or 2mM VPA for 3h didn't. Furthermore, the increased level of hsp70 expression induced by PTZ, a stress marker protein, was significantly reduced in the VPA-pretreated zebrafish brains. Collectively, our data show the antiepileptic effects of VPA in the adult zebrafish, which coincides with reduced hsp70 mRNA expression, rescued learning impairment under PTZ-treated conditions.

Aclidinium bromide, a novel long-acting muscarinic M3 antagonist for the treatment of COPD.

Aclidinium bromide is a novel, inhaled, long-acting antimuscarinic agent being developed by Almirall Prodesfarma SA and Forest Laboratories Inc as a once-daily treatment for COPD. In preclinical studies, aclidinium bromide demonstrated a comparable profile to tiotropium bromide, with a slightly quicker onset of action but shorter duration of action. Clinical trials have demonstrated an unquestionably interesting pharmacological profile characterized by a faster rate of onset of the smooth muscle relaxing activity than tiotropium bromide and a rapid plasma hydrolysis in human plasma to inactive metabolites that may account for its favorable cardiovascular safety profile. However, the disappointing efficacy results of the recent phase III trials have cast doubt on the real advantage of introducing this drug on the market. Discussions with the FDA concluded that more trials are needed to assess selected dosing regimens, including higher and/or more frequent doses. At the time of publication, further phase III trials with aclidinium bromide were ongoing, and the developing companies were also extending development to combinations of aclidinium bromide with formoterol or an undisclosed inhaled corticosteroid.

Mangiferin ameliorates scopolamine-induced learning deficits in mice.

The aim of this study was to evaluate the effects of Anemarrhena asphodeloides BUNGE (AA) on cholinergic memory deficits in mice. This agent has previously been used as an antipyretic, anti-inflammatory, anti-diabetic, and antidepressant in traditional Chinese medicine. Mangiferin was isolated from AA and showed a dose-dependent inhibition of acetylcholinesterase (AChE) activity (IC(50) value, 62.8 microM). Cholinergic dysfunction was induced in mice by administering scopolamine, and the animals were then tested using the passive avoidance test as well as the Morris water maze test. Mangiferin (20 mg/kg, p.o.) significantly reversed scopolamine-induced deficits in the passive avoidance test, and also improved escape latencies in training trials and increased swimming times in the Morris water maze test (p<0.05). Mangiferin also reduced acetylcholine and tumor necrosis factor (TNF)-alpha levels induced by scopolamine in mice brain (p<0.05) and inhibited nuclear factor (NF)-kappaB activation in scopolamine or TNF-alpha-stimulated BV-2 microglial cells. These results suggest that mangiferin can improve long-term cholinergic memory deficits by AChE inhibition or cholinergic receptor stimulation and inhibition of NF-kappaB activation.

Using the zebrafish lateral line to screen for ototoxicity.

The zebrafish is a valuable model for studying hair cell development, structure, genetics, and behavior. Zebrafish and other aquatic vertebrates have hair cells on their body surface organized into a sensory system called the lateral line. These hair cells are highly accessible and easily visualized using fluorescent dyes. Morphological and functional similarities to mammalian hair cells of the inner ear make the zebrafish a powerful preparation for studying hair cell toxicity. The ototoxic potential of drugs has historically been uncovered by anecdotal reports that have led to more formal investigation. Currently, no standard screen for ototoxicity exists in drug development. Thus, for the vast majority of Food and Drug Association (FDA)-approved drugs, the ototoxic potential remains unknown. In this study, we used 5-day-old zebrafish larvae to screen a library of 1,040 FDA-approved drugs and bioactives (NINDS Custom Collection II) for ototoxic effects in hair cells of the lateral line. Hair cell nuclei were selectively labeled using a fluorescent vital dye. For the initial screen, fish were exposed to drugs from the library at a 100-muM concentration for 1 h in 96-well tissue culture plates. Hair cell viability was assessed in vivo using fluorescence microscopy. One thousand forty drugs were rapidly screened for ototoxic effects. Seven known ototoxic drugs included in the library, including neomycin and cisplatin, were positively identified using these methods, as proof of concept. Fourteen compounds without previously known ototoxicity were discovered to be selectively toxic to hair cells. Dose-response curves for all 21 ototoxic compounds were determined by quantifying hair cell survival as a function of drug concentration. Dose-response relationships in the mammalian inner ear for two of the compounds without known ototoxicity, pentamidine isethionate and propantheline bromide, were then examined using in vitro preparations of the adult mouse utricle. Significant dose-dependent hair cell loss in the mouse utricle was demonstrated for both compounds. This study represents an important step in validating the use of the zebrafish lateral line as a screening tool for the identification of potentially ototoxic drugs.

Effects of an aqueous extract of Puerariae flos (Thomsonide) on impairment of passive avoidance behavior in mice.

The effects of an aqueous extract of Puerariae flos (Thomsonide) on ethanol-induced learning and memory impairment and scopolamine-induced amnesia were investigated. Thomsonide exerted an ameliorating effect on the impairment of both memory registration and memory retrieval induced by ethanol. These results indicate that Thomsonide has an antiamnesic effect on the central nervous system in alcoholic intoxication and support the traditional use of Puerariae flos for the treatment of alcoholic intoxication. Thomsonide also improved the scopolamine-induced impairment of memory registration in passive avoidance behavior in mice. The results of this study suggest that it may be possible to use Thomsonide for the treatment of age-related memory impairment and dementia.

New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids.

Five new piperidine alkaloids were designed from natural (-)-3-O-acetyl-spectaline and (-)-spectaline that were obtained from the flowers of Senna spectabilis (sin. Cassia spectabilis, Leguminosae). Two semi-synthetic analogues (7 and 9) inhibited rat brain acetylcholinesterase, showing IC50 of 7.32 and 15.1 microM, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1mg/kg, i.p.) was fully efficacious in reverting scopolamine-induced amnesia in mice. The two active compounds (7 and 9) did not show overt toxic effects at the doses tested in vivo.

Impairment of male fertility induced by muscarinic receptor antagonists in rats.

Male rats were treated with a muscarinic receptor antagonist at 3, 10, and 100mg/kg/day for 4 weeks prior to mating with untreated females and their reproductive status was determined on gestation days (GD) 15-17. Treatment-related decreases in the pregnancy rate were observed at 100mg/kg/day without any effects on mating performance. Impairment of male fertility by this compound was also observed after treatment for 1 week, but there were no effects after a 1-week withdrawal period suggesting reversibility of the effect. There were no treatment-related effects on sperm production or motility, or testicular histopathology in any group. In order to determine whether the reduced fertility was a class effect of muscarinic receptor antagonists, atropine was examined. Males received atropine for 1 week at 62.5 and 125 mg/kg/day and were mated with untreated females. A low pregnancy rate associated with a decrease in the number of implantations was observed at 125 mg/kg/day. The effect on implantation was also observed at 62.5mg/kg/day. These findings suggest that the impairment of fertility in male rats induced by muscarinic receptor antagonists is a class effect, and has a relatively short onset of effect and is quickly reversible.

Hypericum perforatum as a nootropic drug: enhancement of retrieval memory of a passive avoidance conditioning paradigm in mice.

Depression, among other non-cognitive symptoms, is common in patients with dementia. The effect of Hypericum perforatum (St. John's Wort) extract, with well-documented antidepressant activity, was tested on memory retrieval 24 h after training on a one-trial passive avoidance task in mice. Acute administration of Hypericum extract (4.0, 8.0, 12.0, and 25.0 mg/kg i.p.) before retrieval testing increased the step-down latency during the test session. The same doses of Hypericum extract, on the other hand, failed to reverse scopolamine-induced amnesia of a two-trial passive avoidance task. The involvement of serotonergic, adrenergic, and dopaminergic mechanisms in the facilitatory effect of Hypericum extract on retrieval memory was investigated. Pretreatment of the animals with serotonergic 5-HT1A receptor antagonist (-)-pindolol (0.3, 1.0, and 3.0 mg/kg), serotonergic 5-HT2A receptor blocker spiperone (0.01, 0.03, and 0.1 mg/kg), alpha adrenoceptor antagonist phentolamine (1, 5, and 10 mg/kg), beta receptor antagonist propranolol (5, 7.5, and 10 mg/kg), dopaminergic D1 receptor antagonist SCH 23390 (0.01, 0.05, and 0.1 mg/kg), and dopaminergic D2 receptor antagonist sulpiride (5, 7.5, and 10 mg/kg) revealed the involvement of adrenergic and serotonergic 5-HT1A receptors in the facilitatory effect of Hypericum extract on retrieval memory. It is concluded that Hypericum extract may be a better alternative for treatment of depression commonly associated with dementia than other antidepressants known to have anticholinergic side effects causing delirium, sedation and even exacerbating already existing impaired cognition. In dementias of old age, Hypericum perforatum would, therefore, serve as one medication targeting both depression and amnesia with lower potential side effects.

Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia.

In the present study, the effects of vitamins E and C on the levels of neurotransmitters and acetylcholinesterase activity in the brains of rats treated with scopolamine, an inducer of dementia, were examined. Fifty male Sprague-Dawley rats at the age of 5 wk were divided into five groups after 1 wk of adaptation and fed five different diets for 6 wk: a no-scopolamine group, which was a scopolamine-untreated group fed only a basal diet: a scopolamine-treated group fed a basal diet; a vitamin E-supplemented scopolamine-treated group: a vitamin C-supplemented scopolamine-treated group; and a vitamins E and C-supplemented scopolamine-treated group. Scopolamine was twice administered by intraperitoneal injection (300 mg/kg, body weight), 3 d and 20 min prior to sacrifice. Brain acetylcholinesterase activity was markedly reduced by scopolamine injection. However, the supplementation of vitamins E and C in the diet significantly increased the reduced brain acetylcholinesterase activity up to the level of the scopolamine-untreated group. Brain serotonin concentration in the vitamin C-supplemented scopolamine-treated group was significantly higher than that in the scopolamine-treated group. However, there were no significant differences in brain dopamine and norepinephrine concentrations among all groups. In conclusion, supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase activity at the normal level and serotonin concentration for some extent under the condition to induce dementia by scopolamine administration.

Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice.

Polyacetylenic alcohols and their linoleates isolated from Panax ginseng C. A. MEYER and Cirsium japonicum DC., of which the lipophilic extracts had been found to affect the neuritogenesis of cultured paraneurons, were demonstrated to have a significant neuritogenic effect on PC12h and Neuro2a cells. Panaxynol and the acetylenic triol in particular were highly efficient at concentrations > or = 2 microm. Panaxynol (20 mg/kg/d, i.p., for 3 d) was confirmed to improve scopolamine-induced memory deficit in mice (Y-maze task). It is suggested that the promotion of neuritogenesis in cultured paraneurons by the addition of panaxynol is related its ability to improve memory deficits in animals.

[The evaluation of the specific activity and side effects of the m-cholinergic blocker pentifin compared to other antiparkinson agents]. / Otsenka spetsificheskoi aktivnosti i pobochnykh éffektov m-kholinoblokatora pentifina v sravnenii s drugimi antiparkinsonicheskimi sredstvami.

Experiments on rodents showed that pentifin, a muscarine antagonist belonging to the group of acetylene amines, possesses a pronounced antiparkinsonian activity. Pentifin is superior in the breadth of therapeutic action and tolerance characteristics to the conventional agents used for Parkinson's disease treatment.

Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice.

The effects of two ginseng saponins having a different ratio of protopanaxadiol (PD) and protopanaxatriol saponins (PT) on the learning impairment induced by scopolamine, and learning and memory in mice were investigated in a passive avoidance task and a Morris water maze task. The ratio of PD and PT was 1.24 and 1.46, respectively. Before training, the ginseng saponins were administered intraperitoneally at doses of 50 and 100 mg/kg. The two saponins improved the scopolamine-induced learning impairment at different dosages in mice, 50 and 100 mg/kg, respectively. However, the two saponins did not show a favorable effect on learning and memory in normal mice. Korean red ginseng saponin with a low PD/PT ratio had an improving effect on spatial working memory, but the saponin with a high PD/PT ratio did not. This finding suggests that the PD/PT ratio of the ginseng saponins may be an important factor in the pharmacological role of red ginseng as a medicinal herb.