淫羊藿苷对淀粉样β蛋白片段25-35所致大鼠学习记忆障碍的改善作用

目的观察淫羊藿苷对淀粉样β蛋白片段25-35(Aβ25-35)所致阿尔茨海默病(AD)模型大鼠学习记忆能力的保护作用,并探讨其可能的作用机制。方法Wistar雄性大鼠,右侧海马内注射Aβ25-3510μg制备AD模型,次日起淫羊藿苷30,60和120mg.kg-1灌胃给药,连续14d,d15～19Morris水迷宫检测大鼠空间辨别学习记忆能力;d20检测海马组织中谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)及一氧化氮合酶(NOS)的活性,免疫组化法检测海马内乙酰胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的表达。结果与模型对照组比较,淫羊藿苷给药14d明显改善大鼠学习记忆能力;海马组织中SOD和GSH-PX活性升高,NOS活性降低;海马内AChE及ChAT的表达增加。结论淫羊藿苷可以改善Aβ25-35海马内注射所致AD模型大鼠的学习记忆能力,其作用可能与其增加AChE和ChAT表达,增强SOD和GSH-PX等自由基清除酶活性,降低NOS活性,减少NO释放等多种机制,促进胆碱能递质系统功能的恢复有关。     

人参总皂苷联合淫羊藿苷对血管性痴呆大鼠学习记忆及海马神经细胞凋亡的影响研究

目的：研究人参总皂苷联合淫羊藿苷对血管性痴呆大鼠学习记忆、氧自由基及海马CA1区神经细胞凋亡的影响。方法：采用反复夹闭双侧颈总动脉再灌注同时腹腔注射硝普钠方法建立血管性痴呆大鼠模型,连续给药21d后,用八臂电迷宫法判断给药前后大鼠的学习和记忆能力,再进行脑组织SOD、MDA的测定和海马CA1区神经细胞凋亡检测。结果：与假手术组大鼠相比,模型大鼠电迷宫学习和记忆错误次数明显增加（P〈0.05）,大鼠造模前后连续灌胃给药21 d后,大鼠上述行为学指标得到明显改善（P〈0.05）,脑组织SOD活性提高（P〈0.05）和MDA含量降低（P〈0.01）,海马CA1区神经细胞凋亡数减少（P〈0.05）。结论：人参总皂苷联用淫羊藿苷对血管性痴呆大鼠学习记忆障碍有显著的预防和治疗作用,可能与通过改善血管性痴呆大鼠大脑自由基代谢和海马CA1区神经细胞损伤有关,从而起到保护大脑的作用。     

不同采收季节的淫羊藿中朝藿定C和淫羊藿苷的含量比较

目的比较3个贵州主流产淫羊藿药材在不同采收季节中朝藿定C和淫羊藿苷的含量。方法用高效液相色谱（HPLC）法测定粗毛淫羊藿、巫山淫羊藿、黔岭淫羊藿中朝藿定c和淫羊藿苷的含量。采用EliteSinoChromODS—AP柱（250mm×4．6mm,5．0Ixm）,流动相为乙腈（A）一水（B）梯度洗脱（0—22rain,27％_29％A;22～23rain,29％_÷100％A;23～34rain,100％A;34～36rain,loO％一27％A;36～50min,27％A）。结果朝藿定c和淫羊藿苷进样量分别在13．22～396．6Ixg（r=0．9999）和3．026～151．3斗g范围内与峰面积均呈良好线性关系（r=0．9999）,平均回收率均在98．0％一105．O％范围内;粗毛淫羊藿中朝藿定c和淫羊藿苷的含量分别为0．516％～2．973％,0．096％～0．216％;黔岭淫羊藿中朝藿定C和淫羊藿苷的含量分别为0．071％～0．185％,0．081％～0．164％;巫山淫羊藿含朝藿定c和淫羊藿苷中朝藿定c和淫羊藿苷的含量分别为1．015％～4．219％,0．080％～0．190％。结论巫山淫羊藿中朝藿定c和淫羊藿苷的含量最高,其次为粗毛淫羊藿、黔岭淫羊藿,说明不同产地、不同品种的淫羊藿药材中朝藿定c和淫羊藿苷的含量差异较大．     

淫羊藿苷药理研究概况

淫羊藿是小檗科淫羊藿属植物,包括粗毛淫羊藿（Epimedium acuminatum Franch．）、朝鲜淫羊藿（Epimedium koreanum Nakai）、心叶淫羊藿（Epimedium brevicornum Maxim．）、巫山淫羊藿（Epimedium wushanense）、箭叶淫羊藿（Epimedium sagittatum Maxim．）和柔毛淫羊藿（Epimedium pubescens）等。淫羊藿苷（Ica）是淫羊藿中的主要活性成分,分子式为C33H40O15,分子量为676．67。     

粗毛淫羊藿甙的分离和结构

粗毛淫羊藿Epimedium acuminatum Franch为小檗科植物,又名尖叶淫羊藿,分布于四川、云南、贵州和湖北,在当地作淫羊藿药用。对粗毛淫羊藿的化学成分研究尚未见报道。本文报道从四川产粗毛淫羊藿的地上部分分离到五个化合物并进行了结构研究。     

贵州产淫羊藿的质量研究

用ＲＰ－ＨＰＬＣ法，对产于贵州淫羊藿属植物９种２变种的６种主要黄酮类成分分析，确定贵州产的箭叶淫羊藿类群质量最好。另外除药典种类外，粗毛淫羊藿、黔北淫羊藿、不城淫羊藿等可药和，而分布较物黔岭淫羊藿不宜药用。我们建立的高效液相分析方法，可作为淫羊藿属植物的鉴定可靠手段。     

淫羊藿甙防治血管性痴呆的实验研究

目的观察淫羊藿甙(Icariin，ICA)对血管性痴呆(vascular dementia，VD)大鼠学习记忆的保护作用，探讨ICA防治VD的作用机制。方法采用永久性结扎双侧颈总动脉的方法(2-VO法)制作VD大鼠模型，利用Morris水迷宫检测ICA对大鼠空间辨别学习记忆能力的影响；用光化学法检测大脑皮层及海马组织中SOD)活性、     

基于FGFR1靶点分子虚拟对接筛选淫羊藿中抗骨质疏松的药效成分

目的基于FGFR1蛋白靶点筛选淫羊藿中抗骨质疏松的药效成分。方法采用维甲酸灌胃14 d复制大鼠骨质疏松模型,给予淫羊藿提取物进行干预;采用Western blotting法检测各组大鼠股骨FGFR1蛋白的表达,用UPLC-Q-TOF-MS确认提取物中化学成分。基于FGFR1靶点进行分子虚拟对接筛选药效成分。结果淫羊藿能够改善大鼠骨质疏松症状,并提高FGFR1蛋白的表达。淫羊藿提取物中指认出23种化合物,其中淫羊藿苷、淫羊藿次苷I、箭藿苷C可与FGFR1可以有效对接。结论淫羊藿中淫羊藿苷、淫羊藿次苷I、箭藿苷C可能通过上调FGFR1发挥抗骨质疏松作用。     

淫羊藿总黄酮及其含药血清对成骨细胞增殖及功能表达的影响

目的研究淫羊藿总黄酮及其含药血清对体外培养大鼠成骨细胞(ROB)增殖和功能表达的影响。方法将淫羊藿总黄酮(TFE)以0.2、2、20、100、200 mg.L-15种质量浓度、含淫羊藿总黄酮大鼠血清(SRAT)以2%、4%、8%、16%等4种体积浓度分别加入新生大鼠颅骨成骨细胞培养液中,研究其对细胞增殖和功能表达的影响。细胞增殖采用MTT法进行分析,细胞功能表达是于培养d 5、10、15、20分别检测碱性磷酸酶活性(比色法)、骨钙素分泌量(放射免疫法)、钙盐沉积量(比色法)和矿化结节(组织化学法)等。结果TFE5种质量浓度均对ROB细胞增殖和分化无影响,2%和4%SRAT则表现出强烈的刺激细胞增殖活性并提高碱性磷酸酶活性、骨钙素分泌量、矿化结节数和钙盐沉积量。结论淫羊藿治疗骨质疏松的直接物质基础可能并非TFE,而与其经口给予后吸收入血的TFE代谢产物及其诱生物有关。血清中的TFE代谢产物可促进细胞的功能表达增殖。     

药典内5种淫羊藿中黄酮类成分的反相高效液相色谱分析

报道了药典规定的5种淫羊藿──淫羊藿、箭叶淫羊藿、巫山淫羊藿、柔毛淫羊藿和朝鲜淫羊藿中9种黄酮──淫羊藿甙(icariin)、宝藿甙-Ⅰ(baohuosideI)、宝藿甙-Ⅱ(baohuosideⅡ)、淫羊藿甙A(epimedosideA)、箭藿甙B(sagittatosideB)、朝藿定B(epimedinB)、朝藿定C(epimedinC)、大花淫羊藿甙C(ikarisosideC)和大花淫羊藿甙F(ikarisosideF)的反相高效液相色谱测定。色谱柱为DISK-C_phenlyl,流动相为乙腈-乙酸液(水:36%乙酸=100:4),梯度洗脱,检测波长为272nm。     

葡萄籽原花青素对血管性痴呆大鼠空间学习记忆能力的影响

目的观察葡萄籽原花青素(GSP)对血管性痴呆(VD)大鼠空间学习记忆能力的影响,探讨其可能的作用机制。方法采用改良Pulsinelli四血管阻塞法建立VD大鼠模型,造模成功后,每天灌胃给药,Wistar大鼠分为假手术组,模型组,原花青素组(50 mg/kg和150 mg/kg),银杏叶片24 mg/kg。Morris水迷宫检测VD大鼠空间学习记忆能力;比色法检测脑组织超氧化物歧化酶(SOD)活性、总抗氧化能力(T-AOC)、谷胱甘肽(GSH)、丙二醛(MDA)含量;实时荧光定量PCR(Real-time PCR)法检测海马Bax、Bcl-2 mRNA的表达。结果与模型组比较,原花青素可明显改善VD大鼠空间学习记忆能力;提高脑组织SOD活性、GSH含量和总抗氧化能力,降低MDA含量;提高海马Bcl-2/Bax mRNA比值。结论原花青素可改善VD大鼠学习记忆功能,其机制可能与提高机体抗氧化能力、抑制海马神经元凋亡有关。     

二苯乙烯苷对慢性脑缺血大鼠学习记忆的影响

目的观察何首乌有效成分二苯乙烯苷(TSG)对慢性脑缺血大鼠学习记忆能力的影响,并探讨其可能机制。方法雄性SD大鼠双侧颈总动脉永久性结扎制备慢性脑缺血致痴呆模型。术前2周起,分别给TSG30,60及120mg·kg-1·d-1,ig,连续11周。术后8周时,分别用Morris水迷宫实验和避暗实验检测大鼠的空间学习记忆能力和被动回避学习记忆能力。术后9周时,采用生化方法检测海马乙酰胆碱酯酶(AChE)活性,免疫组化方法检测海马蛋白磷酸酶2A(PP-2A)和微管相关蛋白2(MAP-2)的表达。结果慢性脑缺血模型组大鼠空间和被动回避学习记忆能力明显降低,海马AChE活性显著升高,PP-2A和MAP-2表达明显减少。TSG给药10周可显著改善慢性脑缺血引起的学习记忆能力降低;给药11周明显抑制海马AChE活性增高,并增加PP-2A和MAP-2的表达。结论TSG可改善慢性脑缺血大鼠的学习记忆能力,其机制可能与抑制海马AChE活性,增加海马PP-2A和MAP-2的表达有关。     

阿魏酸对血管性痴呆大鼠学习记忆障碍的改善作用及其机制研究

血管性痴呆(vascular dementia,VD)是一种严重威胁老年人生命健康的神经退行性疾病,随着人口的老龄化,VD发病率逐年上升,寻找安全有效的抗VD药物已成为药物研究的热点[1,2]。近年来,中医药以活血化瘀法治疗VD取得了较大进展[3?5]。川芎是一种典型的活血化瘀中药,始载于《神农本草经》,具有活血行气、祛风止痛的功效,广泛用于VD     

Ameliorative Effect of a Selective Endothelin ETA Receptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia

The present study was designed to investigate the efficacy of selective ET_A receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from 5^th to 8^th week of L-methionine treatment). On 52^nd day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective ET_A receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.     

Protective roles of <Emphasis Type="Italic">N</Emphasis>-benzylcinnamide on cortex and hippocampus of aged rat brains

Brain aging has been associated with oxidative stress leading to inflammation and apoptosis. The protective effects and underlying mechanisms of N-benzylcinnamide (PT-3), purified from Piper submultinerve, on brains of 90-week-old Wistar rats were investigated following daily intraperitoneal injection with 1.5 mg of PT-3/kg of body weight for 15 days. PT-3 treatment improved spatial learning and memory of aged rats and caused significant changes in brain frontal cortex, hippocampus, and temporal cortex in parameters associated with oxidative stress (decreased reactive oxygen species production and iNOS and nNOS levels), inflammation (reduced levels of IL-1β and IL-6), apoptosis (reduced levels of Bax and activated caspase-3, and elevated level of Bcl-2), and signaling pathways related to inflammation and apoptosis (decreased amounts of phospho-JNK and -p38, increased phospho-Akt level and no change in phospho-ERK1/2 content) compared to controls. PT-3 treatment also inhibited aged rat brain AChE activity. These results suggest that PT-3 with its intrinsic antioxidant and AChE inhibitory properties has therapeutic potential in ameliorating, in part, age-associated damages to the brain.     

如意珍宝片对血管性痴呆模型大鼠的保护作用

目的 研究如意珍宝片对血管性痴呆(VD)大鼠的保护作用。方法 采用改良双侧颈总动脉永久性结扎法制备大鼠VD模型,以Y迷宫为学习记忆评价指标,并测定VD大鼠脑内多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)3种单胺类神经递质水平。结果 如意珍宝片能显著的增加Y迷宫的正确次数和提高脑内3种单胺类神经递质水平。结论 如意珍宝片能提高VD大鼠学习记忆能力,升高脑内单胺类神经递质水平,从而改善大脑皮层的兴奋性,激活脑损伤后的学习记忆过程。     

益智康脑丸对老年性痴呆大鼠行为学及脑组织Bcl-2和Bax蛋白表达的影响

目的:探讨益智康脑丸对老年性痴呆(AD)大鼠行为学及脑组织凋亡蛋白的影响。方法:复制D-半乳糖AD大鼠模型。实验分为4组,即空白、模型、益智康脑丸和脑复康组,检测大鼠行为学及脑组织抑制细胞凋亡基因Bcl-2和促凋亡基因Bax表达指标的改变。结果:模型组与空白组比较,学习记忆能力显著下降,Bcl-2/Bax比值下降;治疗组与模型组比较,学习记忆能力显著改善,Bcl-2/Bax比值增加。结论:益智康脑丸具有较好的治疗AD作用,其机制可能与促进AD大鼠脑组织Bcl-2的表达、降低Bax的表达有关。     

Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat

Curcumin, the principal curcuminoid of turmeric, exhibits beneficial role in several neurodegenerative disorders such as dementia of Alzheimer type. Recent evidences suggest the involvement of brain insulin receptors (IRs) in the pathophysiology of dementia disorders. Therefore, the present study was undertaken to investigate the effect of curcumin on memory functions, brain IRs, acetylcholinesterase (AChE) activity and oxidative stress in intracerebroventricular (ICV) administered streptozotocin (STZ) induced dementia in rats. Rats were injected with STZ (3 mg/kg, ICV) bilaterally twice, on day 1 and 3 and curcumin (200 mg/kg, po) was administered in pre- and post-treatment schedules. STZ (ICV) treated group had shown memory deficit as indicated by no significant decrease in latency time in Morris water maze test and significant decrease in IR protein level in both hippocampus and cerebral cortex. Pre- and post-treatment of curcumin in STZ (ICV) treated rats significantly restored the memory deficit and IR protein level in both the regions. Furthermore, STZ (ICV) resulted into enhanced AChE activity in hippocampus and cerebral cortex which was normalized by curcumin pre- and post-treatment. An increase in MDA level and decrease in GSH level were obtained in both hippocampus and cerebral cortex in STZ treated group, indicating state of oxidative stress, which was also attenuated by pre- and post-treatment of curcumin. The results suggest that besides the anticholinesterase and antioxidant activity, effect on brain IR may also be an important factor for protective effect of curcumin against STZ induced dementia model.     

Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil

Present study was designed to investigate modulation of experimental dementia by Pitavastatin and donepezil. Learning and memory of the swiss albino mice were studied on Morris water-maze. Celecoxib orally (p.o.)/Streptozotocin (STZ) intracerebroventricular administrations were used to induce experimental dementia. Brain acetyl cholinesterase activity was measured by EllMann's method to assess cholinergic activity of the brain. Brain thio barbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively, to assess total oxidative stress in brain. Total serum cholesterol level was measured by Allain's method. Celecoxib/STZ treatments produced a significant loss of learning and memory. Pitavastatin/Donepezil successfully attenuated this Celecoxib/STZ induced dementia. Higher levels of brain acetyl-cholinesterase (AChE) activity, TBARS and lower level of GSH were observed in Celecoxib/STZ treated animals, which were significantly attenuated by Donepezil. Pitavastatin also attenuated the Celecoxib/STZ induced high levels of TBARS & low levels of GSH without effecting AChE activity and total serum cholesterol levels. Celecoxib induced dementia noted in the present study may be attributed to its stimulatory effect on amyloid beta-42, brain AChE activity, and oxidative stress. Sub-diabetogenic STZ induced memory deficits closely related to Alzheimer's disease. Reversal of Celecoxib/STZ induced memory deficits by Pitavastatin may be due to its antioxidative, anti beta amyloid aggregatory property, and by Donepezil, due to its anticholinesterase and neuroprotective actions.     

Experimental study of icariin on vascular dementia in rats induced by 2-VO method

AIM: To study the effects of icariin (ICA) on the learning and memory of ischemic vascular dementia (VD) model of rats,and explore the protective mechanisms. METHODS: ICA was administered to the VD model rats induced by a permanent bilateral occlusion of both common carotids arteries(2-VO method) and by cerebral ischemia-reperfusion (I10-R 10-110 method). Morris water maze was used to examine the abilities of spatial learning and memory of VD model rats. The activity of SOD, level of