Effects of ginseng total saponin on morphine-induced hyperactivity and conditioned place preference in mice

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.     

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.     

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.     

逍遥散对慢性温和应激模型小鼠行为学及空间学习记忆能力的影响

目的:研究逍遥散对慢性温和应激模型小鼠行为学与空间学习记忆能力的影响,为其临床用于治疗抑郁症提供药理学依据。方法:采用慢性温和不可预见性的应激方法建立小鼠抑郁症模型,并于造模2周后开始给予逍遥散(30、20g/kg)进行治疗,同时继续造模4周。于造模后不同时间点测定小鼠体重、自主活动和糖水消耗量等行为学指标;并用Morris水迷宫测试小鼠空间学习记忆能力。结果:⑴经过6周的造模程序,与正常对照组比较,模型组小鼠体重增长缓慢(P<0.01),活动次数明显减少(P<0.05),糖水消耗量显著降低(P<0.01);而与模型组比较,逍遥散30g/kg组能使小鼠体重增长数明显增高(P<0.05),逍遥散30、20g/kg能增加模型小鼠的活动次数(P<0.05),并且在治疗3、4周时显著提高模型小鼠的糖水消耗量(P<0.05)。⑵经过6周的造模程序,与正常组比较,模型组小鼠学习记忆成绩及穿越原平台时间占总时间的百分比显著降低(P<0.01或P<0.05)。给予逍遥散30、20g/kg治疗4周后模型小鼠的学习记忆成绩明显提高(P<0.05),并表现出增加小鼠穿越原平台象限时间百分比的趋势。结论:逍遥散能改善慢性轻度应激模型小鼠体重、自主活动与糖水消耗量的异常,并能提高其空间学习记忆能力,表现出抗抑郁作用。     

Therapeutic effect of Korean red ginseng on inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury

This study aims to identify the therapeutic effect of Korean red ginseng (KRG) on the expression of inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) for two hours. They were fed KRG extract (100 mg/kg/day per orally) or saline after reperfusion. Tests for neurological deficits, using the modified neurologic severity score and the corner turn test, were performed before the ischemic event, and one, three, and seven days after tMCAO. Serum levels of cytokines were measured three and seven days after the operation, using enzyme-linked immunosorbent assays. The infarct volume was assessed after seven days by staining brain tissue with 2% 2, 3, 5-triphenyltetrazolium chloride. Oral administration of KRG significantly reduced the infarct volumes and rapidly improved neurological deficits. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were higher in tMCAO-operated rats than in the sham-operated rats. These changes were attenuated by daily KRG intake for seven days. Serum IL-10 levels were significantly increased in KRG-fed rats, as compared to sham-operated and saline-fed rats. Our results suggested that KRG provides neuroprotection for rats with focal cerebral ischemia/reperfusion injury. This neuroprotection may be due to raised IL-10 expression and a reduction in the serum levels of TNF-α, IL-1β, and IL-6.     

芍药苷对小鼠学习记忆能力的影响

目的:观察芍药苷对东莨菪碱致小鼠记忆形成障碍、亚硝酸钠致记忆巩固障碍和乙醇致记忆再现障碍的影响。方法:采用小鼠跳台法和Y型迷宫法。结果:芍药苷7.5、15、30mg/kgiv3日对小鼠学习记忆功能有明显的促进作用,对东莨菪碱致小鼠记忆形成障碍、亚硝酸钠致记忆巩固障碍和乙醇致记忆再现障碍有明显的改善作用,且呈一定的剂量依赖关系。结论:芍药苷对东莨菪碱、亚硝酸钠和乙醇致小鼠记忆获得、巩固及再现障碍均有不同程度的改善作用。     

南沙参多糖改善东莨菪碱所致大鼠学习记忆障碍的研究

目的：探讨南沙参多糖（RAPS）对东莨菪碱所致大鼠学习记忆障碍的影响。方法：igRAPS500－2000mg/kg每天一次共15天,大鼠穿梭箱法测定学习记忆能力,化学荧光法测定单胺类递质的含量。结果：大鼠主动回避反应率显增加;大鼠脑中NE、DA、5－HT含量增加,AchE活性降低;血糖含量增加。结论：RAPS具有改善大鼠学习记忆的功能,其作用与影响鼠脑中神经递质及血糖有关。     

紫苏子油对小鼠学习记忆能力的影响

分别给予幼龄小鼠灌胃不同剂量的紫苏子油，连续１５ｄ，可减少小鼠跳台错误次数，能明显提高小鼠水迷路测验的正确百分率，缩短到达终点时间，并能促进小鼠脑内核酸及蛋白质的合成，调节小鼠脑内单胺类神经递质水平。结果提示紫苏子油能促进小鼠学习记忆能力并与小鼠脑内的核酸，蛋白质及单胺类神经递质含量有关。     

艾灸对缺氧缺血性脑病新生小鼠学习记忆的影响

目的:观察艾灸对缺氧缺血性脑病(HIE)新生小鼠脑组织磷酸化钙调蛋白依赖性蛋白激酶 Ⅱ α(pCaM KⅡα)、神经元核抗原(NeuN)表达和学习记忆的影响,探讨艾灸的作用机制.方法:将出生7 d的ICR小鼠随机分为假手术组、模型组和艾灸组.采用右颈总动脉结扎联合缺氧的方法制备新生HIE动物模型.艾灸组小鼠于"大椎"处...     

大豆异黄酮活性组分对阿尔茨海默病小鼠学习记忆能力的影响

目的探讨大豆异黄酮活性组分对阿尔茨海默病(AD)小鼠学习和记忆能力的改善作用。方法以D-半乳糖和三氯化铝建立AD动物模型,利用Y-型迷宫进行被动回避反应和信号方位辨别反应测试,观察大豆异黄酮活性组分对小鼠学习记忆能力及信号方位辨别能力的影响。结果实验组小鼠学习能力和记忆力均显著优于模型对照组(P<0.01)。结论大豆异黄酮活性组分能有效改善AD小鼠的学习和记忆能力。     

肉苁蓉多糖对小鼠学习记忆的影响

目的 观察肉苁蓉多糖对不同类型学习记忆障碍模型小鼠空间学习记忆能力的影响,探讨其作用机制.方法 120只小鼠按随机数字表法分为空白组,模型组,肉苁蓉多糖小、中、大剂量组,吡拉西坦组,每组20只.肉苁蓉多糖小、中、大剂量组分别灌胃肉苁蓉多糖溶液25、50、100 mg/kg,吡拉西坦组灌胃吡拉西坦10 mg/kg,空白组和模型组灌胃等体积蒸馏水.1次/d,连续给药6周.分别采用环己米特建立小鼠巩固性记忆障碍模型,采用乙醇建立小鼠再现性记忆障碍模型,采用水迷宫检测各组小鼠学习记忆能力,ELISA法检测各组小鼠脑组织内总蛋白、MDA、SOD水平.结果 与环己米特模型组比较,肉苁蓉多糖中、大剂量组逃避潜伏期[(9.45±2.86)s、(12.73±10.89)s比(48.15±30.33)s]、第1次到达站台时间[(19.33±3.27)s、(13.81±9.79)s比(40.71±16.76)s]缩短(P<0.05),肉苁蓉多糖小剂量组第1次到达站台时间[(11.58±7.04)s比(40.71±16.76)s]缩短(P<0.05),穿越站台次数[(5.46±2.09)次比(3.03±1.47)次]增加(P<0.05),肉苁蓉多糖大剂量组脑组织总蛋白含量[(0.76±0.25)g/L比(0.55±0.12)g/L]增加(P<0.05).与乙醇模型组比较,肉苁蓉多糖小、中、大剂量组逃避潜伏期[(22.67±18.35)s、(22.15±16.22)s、(18.00±13.44)s比(51.33±22.19)s]、第1次到达站台时间[(16.70±11.25)s、(19.75±14.62)s、(9.47±5.46)s比(30.09±13.63)s]缩短(P<0.05),肉苁蓉多糖小、大剂量组穿越站台次数[(5.15±1.28)次、(4.83±0.75)次比(1.34±0.83)次]增加(P<0.05),肉苁蓉多糖大剂量组脑组织总蛋白[(0.76±0.25)g/L比(0.56±0.12)g/L]含量增加(P<0.05).结论 肉苁蓉多糖可明显改善小鼠再现性记忆障碍、巩固性记忆障碍,其机制与促进脑内蛋白质合成有关.     

西红花苷对阿尔茨海默病大鼠空间学习记忆的影响

目的:探讨西红花苷对阿尔茨海默病(alzheimer's disease,AD)大鼠空间学习记忆的影响及机制。方法:72只SD大鼠随机分为正常对照组、模型对照组、白藜芦醇组(40mg/kg)和西红花苷低(20mg/kg)、中(40mg/kg)、高(80mg/kg)剂量组。侧脑室微量注射5μl Aβ25-35建立AD大鼠模型,从次日开始每天于固定时间给药,正常对照组和模型对照组注入等量的生理盐水,剂量均为10μl,连续注射14d。利用Morris水迷宫对大鼠进行行为学试验,检测血清活性氧基团(ROS)、超氧化物歧化酶(SOD)和丙二醛(MDA)的含量,免疫组化实验检测海马CA3区和前额叶皮层GAP-43蛋白的表达。结果:Morris水迷宫实验中,模型对照组大鼠逃避水下平台的潜伏期时间较正常组显著延长;白藜芦醇组和西红花苷各剂量组寻找水下平台的潜伏期时间从d2起,较模型对照组均显著缩短;西红花苷40、80mg/kg组潜伏期时间均显著短于20mg/kg组,但与白藜芦醇组之间在各实验日的潜伏期均未见有无显著性统计学差异。血清氧化应激因子的检测,白藜芦醇组和西红花苷各剂量组大鼠血清ROS、MDA含量均显著性高于正常组,低于模型对照组,SOD的变化与此相反。免疫组化实验中,白藜芦醇组和西红花苷各剂量组大鼠海马CA3区和前额叶皮层GAP-43的表达显著性低于正常组,高于模型对照组。结论:西红花苷可能通过抗氧化和增加海马及前额叶皮层GAP-43的表达对AD大鼠空间辨别性学习记忆能力有一定的改善作用。     

Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice

Aim of the study

Yokukansan (YKS) is a Japanese traditional herbal medicine and has been used for the treatment of the behavioral and psychological symptoms of dementia (BPSD). The present study aimed to clarify the effects of YKS on learning and memory impairments, and its mechanisms of action in olfactory bulbectomized (OBX) mice, one of the animal models of Alzheimer's disease (AD).

Materials and methods

OBX or sham-operated ddY mice were treated with YKS or donepezil (DPZ), a reference drug, and their cognitive performances were tested by the modified Y-maze test, novel object recognition test, and fear conditioning test to elucidate the spatial working memory, non-spatial short-term memory, and long-term memory, respectively. After completing the behavioral experiments, the expression level of cholinergic marker proteins and the activity of acetylcholinesterase (AChE) in the brain were analyzed by western blotting and Ellman's method, respectively.

Results

OBX caused spatial working memory and non-spatial working memory impairments that were reversed by YKS and also by DPZ; however, YKS failed to affect the long-term memory deficits. Amelioration of the spatial working memory by YKS was reversible by scopolamine, a muscarinic receptor antagonist. YKS treatment reversed OBX-induced down-regulation of choline acetyltransferase and muscarinic muscarinic M₁ receptor expression without affecting muscarinic M₃ receptor expression or AChE activity.

Conclusion

These results demonstrate that YKS improves short-term memory deficit caused by OBX and that the effect is at least partly mediated by muscarinic receptor stimulation and the normalization of central cholinergic systems. The present findings also suggest that YKS has a therapeutic effect not only on BPSD, but also on memory impairment of AD.     

类叶升麻苷对东莨菪碱致小鼠学习记忆障碍的改善作用

目的:探讨类叶升麻苷对痴呆小鼠学习记忆的影响.方法:连续灌服类叶升麻苷10d后,以东莨菪碱建立小鼠记忆获得性障碍模型,采用行为学实验(跳台法)检测动物学习记忆能力,行为学测试结束后,进行小鼠大脑皮层和海马组织中生化指标检测,包括谷胱甘肽过氧化物酶(GSH-Px)、总超氧化物歧化酶(T-SOD)、丙二醛(MDA)、乙酰胆碱酯酶(TChE)以及脑组织蛋白含量的测定.结果:预先给予小鼠类叶升麻苷10 d可以改善东莨菪碱导致的记忆获得性障碍,与模型组比较,类叶升麻苷可显著延长小鼠跳台潜伏期,减少跳台错误次数;类叶升麻苷可使小鼠脑组织中T-SOD,GSH-Px,TChE活性、脑组织蛋白含量升高,MDA含量降低.结论:类叶升麻苷对东莨菪碱致小鼠学习记忆获得性障碍具有显著的改善作用,其作用机制可能与其对抗小鼠体内自由基生成以及改善中枢胆碱能系统功能有关.     

Effects of Korean red ginseng extract on the prevention of atopic dermatitis and its mechanism on early lesions in a murine model

Ethnopharmacological relevance

Korean red ginseng (KRG) has been shown to possess various biological activities including anti-inflammatory properties.

Aim of the study

We aimed to investigate the effects and mechanism of KRG on the prevention of atopic dermatitis (AD) using a mouse model.

Materials and methods

The effect of KRG in trinitrochlorobenzene (TNCB)-treated NC/Nga mice was assessed by measuring ear thickness, transepidermal water loss (TEWL), total serum IgE, histologic changes of lesional skin, mRNA and protein expression of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor (TNF)-α, immunohistochemistry for tissue interleukin (IL)-4, IL-17, and interferon (IFN)-γ.

Results

KRG significantly reduced ear thickness. Oral administration of KRG significantly prevented the increase in TEWL induced by TNCB. The serum IgE level was significantly lower in the KRG group. Histologically, lymphocyte infiltration was markedly decreased by KRG. CD1a positive (CD1a+) cells were diminished by KRG. Immunohistochemically, KRG significantly suppressed the protein expression of TSLP and TNF-α. The mRNA expression of TSLP in the lesions was significantly reduced by KRG. These results demonstrate that oral administration of KRG may inhibit the development of AD-like skin lesions in NC/Nga mice by modifying TSLP, DCs, and at least in part, the Th2 response.

Conclusion

KRG may be a potential therapeutic modality for the prevention of AD.     

Age- and individual-related specificities in the effects of standardized ginseng extract on learning and memory (experiments on rats)

Using a two-way active avoidance with punishment (electric shock) reinforcement (shuttle box) we investigated the effects of Panax ginseng extract, standardized according to the content of ginsenosides on learning and memory in 2-, 10-, and 22-month old Wistar rats and in rats of the same age (5-month old) which, after a preliminary training with the same method, had been classified as ‘good’, ‘poor’ and ‘satisfactory’ learners. In experiments on rats of different ages G115 was administered orally daily for 10 consecutive days before training at increasing doses of 3, 10, 30 and 100 mg/kg body weight. The animals were trained for 5 days and the retention test was given 14 days after the last administration of G115 (10 days after the last training session). In experiments on rats with different learning capabilities G115 was administered orally at a dose of 10 mg/kg for 10 days after shuttle box training. The retention test was performed on the day following the last treatment with G115. It was found that G115 exerted the most favourable effects on learning and memory when these processes were decayed as a result either of senescence or of individual specificities.     

三七总皂苷对糖尿病小鼠空间认知功能改善及海马神经的保护作用研究

目的:评价三七总皂苷(PNS)对糖尿病模型小鼠空间学习记忆能力改善及海马神经的保护作用。方法:45只昆明种小鼠随机分为正常对照组(NC组)、模型组(DM组)、PNS治疗组(PNS组),每组15只。PNS组按200 mg/kg剂量灌胃给予PNS水溶液,其余两组给予等量双蒸馏水灌胃,每天1次,连续30 d。对各组动物进行Morris水迷宫学习记忆行为学检测及对大脑海马进行病理学分析。结果:定位航行实验中,与DM组比较,PNS组逃避潜伏期明显缩短(P<0.05);空间探索实验中,与DM组比较,PNS组表现出较好的原平台搜索策略,可延长其目标象限游泳时间(P<0.01);病理结果显示:PNS组神经元形态和数量均有不同程度的改善,神经元数量与DM组比较有显著性差异(P<0.01)。结论:三七总皂苷对糖尿病模型小鼠空间认知功能有改善作用,对海马神经具有一定保护作用。