Effect of cerebralcare granule®combined with donepezil on Alzheimer’s disease

Background:The current prevalence of Alzheimer’s disease(AD)in the elderly has risen from 1%at 65 to 40%to 50%at 95,and the overall proportion is rising.Emerging evidence suggests that ros-driven oxidative stress is a crucial mediator of the aging process.Thus,in recent years,oxidative damage and inflammation have become targets for exploring pharmacological strategies for treating age-related diseases.Methods:In C57BL/6J mice,to determine whether the mechanism of action of cerebralcare granule®(CG)combined with donepezil(Don)treatment is better than dementia alone,we constructed a mouse model and treated it with CG in combination with Don.Results:A combination of Don and CG significantly reduces the damage caused by lipid peroxidation in the hippocampus of AD mice,reduces oxidative damage,and reduces inflammation,increases the activity of antioxidant enzymes,which is finally manifested as the improvement effect on the learning and memory impairment of AD mice.Conclusion:CG combined with Don has a better effect on improving cognitive and behavioral deficits caused by D-galactose in AD mice than Don alone.The mechanism may be related to reducing inflammation via the NF-κB pathway,resisting oxidative damage and increasing acetylcholine levels.

Bushen Yizhi Formula regulates the IRE1αpathway to alleviate endoplasmic reticulum stress in an Alzheimer’s disease rat model

While the Bushen Yizhi Formula can treat Alzheimer’s disease(AD),the yet to be ascertained specific mechanism of action was explored in this work.Methods:Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide(Aβ)were used to treat rat pheochromocytoma cells(P12)and human neuroblastoma cells(SH-SY5Y).Cell morphological changes were observed to determine the in vitro cell damage.Cell Counting Kit(CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle,respectively.Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress(ERS)-related proteins(GRP78 and CHOP),p-IRE1α,IRE1α,ASK1,p-JNK,JNK,Bax,Bcl-2,XBP-1,and Bim.Fura 2-acetoxymethyl ester(Fura-2/AM)was used to determine the intracellular calcium(Ca^(2+))concentration.Also,an AD model was constructed by injecting Aβinto the CA1 area of the hippocampus in Sprague Dawley rats.AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days.The Morris water maze experiment was conducted to test the learning and memory of rats.Hematoxylin&Eosin(H&E)and Terminal-deoxynucleotidyl Transferase(TdT)-mediated dUTP Nick-End Labeling(TUNEL)staining were done to determine histopathological changes in the brain.Results:Bushen Yizhi Formula relieved the Aβ-induced effects including cell injury,decreased viability,increased apoptosis,G0/G1 phase cell cycle arrest,upregulation of GRP78,CHOP,p-IRE1α,p-JNK,Bax,XBP-1 and Bim,as well as down-regulation of Bcl-2.These results were also seen with IRE1αsilencing.While Aβsuppressed the learning and memory abilities of rats,the Bushen Yizhi Formula alleviated these effects of Aβ.Brain nerve cell injury induced by Aβcould also be treated with Bushen Yizhi Formula.Conclusion:Bushen Yizhi Formula could influence ERS through the IRE1αsignaling pathway to achieve its therapeutic effects on AD.

Yizhijiannao Granule and a combination of its effective monomers,icariin and Panax notoginseng saponins,inhibit early PC12 cell apoptosis induced by beta-amyloid(25-35)

One of our previous studies showed that Yizhijiannao Granule,a compound Chinese medicine, effectively improved the clinical symptoms of Alzheimer’s disease.In the present study,we established a model of Alzheimer’s disease using beta-amyloid（25-35）in PC12 cells,and treated the cells with Yizhijiannao Granule and its four monomers,i.e.,icariin,catechin,Panax notoginseng saponins,and eleutheroside E.Flow cytometry showed that Yizhijiannao Granule-containing serum, icariin,Panax notoginseng saponins,and icariin＋Panax notoginseng saponins were protective against beta-amyloid（25-35）-induced injury in PC12 cells.Icariin in combination with Panax notoginseng saponins significantly inhibited early apoptosis of PC12 cells with beta-amyloid （25-35）-induced injury compared to icariin or Panax notoginseng saponins alone.The effects of icariin＋Panax notoginseng saponins were similar to the effects of Yizhijiannao Granule.The findings indicate that two of the effective monomers of Yizhijiannao Granule,icariin and Panax notoginseng saponins,can synergistically inhibit early apoptosis of PC12 cells induced by beta-amyloid（25-35）.

Shenqi Xingnao Granules ameliorates cognitive impairments and Alzheimer’s disease-like pathologies in APP/PS1 mouse model

Objective:Alzheimer’s disease(AD)is along with cognitive decline due to amyloid-β(Aβ)plaques,tau hyperphospho rylation,and neuron loss.Shenqi Xingnao Granules(SQXN),a traditional Chinese medicine,significantly ameliorated the cognitive function and daily living abilities of patients with AD.However,till date,no study has investigated the mechanism of action of SQXN on AD.The present study aimed to verify the effects of SQXN treatment on cognitive impairments and AD-like pathologies in APP/PS1 mice.Methods:Four-month-old APP/PS1 transgenic(Tg)mice were randomly divided into a model group and SQXN-treated(3.5,7,14 g/kg per day)groups.Learning-memory abilities were determined by Morris water maze and object recognition test.All mice were sacrificed and the brain samples were collected after 75 d.The soluble Aβcontents were detected by Elisa kit;The levels of expression of NeuN,APP,phosphorylated tau and related protein were measured by Western blotting;The inflammation factors were detected by the proinflammatory panel kit.Results:Four-month-old APP/PS1 mice were administered SQXN by oral gavage for 2.5 months.Using the Morris water maze tests and Novel object recognition,we found that SQXN restored behavioral deficits in the experimental group of Tg mice when compared with the controls.SQXN also inhibited neuronal loss(NeuN marker).SQXN treatment decreased soluble Aβ42 through inhibiting the expression of sAPPβand BACE-1 without regulating full-length amyloid precursor protein(FL APP).Insulin degrading enzyme(IDE),the Aβdegrading enzyme,were increased by SQXN.In addition,SQXN reduced hyperphosphorylated tau protein levels and prevented excessive activation of p-GSK-3βin the brain of APP/PS1 mice.Compared with APP/PS1 transgenic negative mice,IFN-γ,IL-1β,IL-2,IL-4,IL-5,IL-6,IL-12 p70,KC/GRO and TNF-αwere not obviously changed in the brain of 6.5-month-old APP/PS1 transgenic(Tg)mice.However,SQXN could inhibited the expression of IL-2.Conclusion:These results demonstrate that SQXN ameliorates the cognitive impairments in APP/PS1 mice.The possible mechanisms involve its inhibition of neuronal loss,soluble Aβdeposition,tau hyperphosphorylation and inflammation.

Neuroprotective Effects of Tongmai Yizhi Decoction(通脉益智汤)against Alzheimer's Disease through Attenuating Cyclin-Dependent Kinase-5 Expression

Objectives： To explore the protective effects of Tongmai Yizhi Decoction（通脉益智汤, TYD）, a Chinese herb complex prescription against the impairment of cognitive functions and memory loss in amyloid beta 1–40（Aβ1-40） peptide and ibotenic（IBO）-induced Alzheimer＇s disease（AD） model rats. Methods： The in vivo model was established by injecting Aβ1-40 and IBO into left hippocampal CA1 area of Sprague-Dawley（SD） rat to mimic AD. Totally 32 SD rats were divided into 4 groups, including sham operation group, AD model group, TYD group [AD rats treated with TYD at the dosage of 19.44 g/（kg·d） for 4 weeks] and huperzine A group [AD rats treated with huperzine A at the dosage of 40.5 μg/（kg·d） for 4 weeks]. Spatial learning and memory level was detected by Morris Water Maze test. Histological morphology in the hippocampus was tested by hematoxylin-eosin（HE） staining. Cyclin-dependent kinase-5（Cdk5） protein and gene expression level were investigated by Western blot analysis and real-time quantitative polymerase chain reaction（RT-q PCR）, respectively. Results： Aβ1-40 and IBO treatment induced longer escape latency of rats, compared with sham operation group from day 25（P〈0.01）. However, TYD and huperzine A obviously shortened the escape latency from day 26（P〈0.01）. Moreover, the effect of TYD was similar to huperzine A（P〉0.05）. Furthermore, HE staining also showed that TYD and huperzine A reversed the neuropathological changes in the hippocampus triggered by Aβ1-40 and IBO. TYD and huperzine A effectively reduced the expression levels of Cdk5 protein and gene located in rat hippocampus, compared with the AD model group（P〈0.01）. Conclusion： TYD could be a promising neuroprotective agent for protecting neuron from AD injury through inhibiting Cdk5 expression.

益智健脑颗粒对SAMP/8快速老化小鼠行为学及神经元凋亡的影响

目的:检测益智健脑颗粒浓缩液(YCF)对SAMP/8快速老化小鼠模型行为学、海马神经元凋亡率及凋亡基因Bc l-2和Bax表达的影响,探讨益智健脑颗粒浓缩液改善学习记忆能力的部分作用机制。方法:6月龄SAMP/8快速老化小鼠模型随机分为中药组、西药组、老年对照组,4月龄SAMP/8作为青年对照组,各组给予不同药物干预,8周后水迷宫实验观察行为学改变,应用流式细胞技术、逆转录-聚合酶链反应(RT-PCR)方法测定海马神经元凋亡率和Bc l-2和Bax mRNA的表达。结果:与老年对照组相比,中药组逃避潜伏期缩短,跨平台象限次数增多,凋亡率显著降低;Bc l-2 mRNA表达上调,Bax mRNA表达下调,Bc l-2 mRNA/Bax mRNA相对表达量比率增高。结论:中药益智健脑颗粒能促进Bc l-2表达,抑制Bax的表达,维持Bc l-2/Bax的平衡,降低凋亡率,这可能是其改善SAMP/8快速老化小鼠学习记忆能力的部分作用机制。

益智清心方单次给药毒性试验研究

目的:观察24 h内益智清心方经口灌胃后的急性毒性反应和死亡情况,评价益智清心方的安全性,为进一步的重复给药毒性试验以及临床用药提供参考。方法:选取24~33 g ICR小鼠,雌雄各半,随机分为益智清心方组和空白对照组,采用最大给药量法,以最大灌胃体积40 mL/kg计,分别给予等体积的益智清心方药液和纯水,2次/d,给药期间定期监测小鼠一般状况和体质量,14 d后,收集血、尿样本,并进行大体解剖,评价益智清心方对脏器系数、血常规、尿常规等安全性指标的影响。结果:ICR小鼠按40 mL/kg经口灌胃给予最大可配制浓度为0.36 g干浸膏/mL的益智清心方药液,当日2次,累积剂量为98.6 g生药/kg体质量,约相当于成人临床拟用剂量的298倍(按公斤体质量计算)和38倍(按体表面积计算)。各组小鼠均未发现毒性相关的症状和死亡,益智清心方组小鼠在体质量、脏器系数、血常规、尿常规指标方面与对照组小鼠比较差异均无统计学意义(均P>0.05)。结论:本试验条件下,益智清心方的单次给药毒性试验中未见明显的急性毒性反应及死亡,提示其最大耐受量(MTD)>98.6 g生药/kg体质量。

益智健脑颗粒对快速老化小鼠SAMP8海马Pin1和HMGB1 mRNA表达的影响

目的:研究益智健脑颗粒对快速老化小鼠SAMP8海马肽基脯氨酰顺反异构酶(peptidylprolyl-cis-trans isomerase A,Pin1)和高迁移率族蛋白B1(high mobility group box1,HMGB1)mRNA表达的影响。方法:6月龄快速老化小鼠SAMP8随机分为中药治疗组和模型组,6月龄正常老化小鼠SAMR1为正常对照组。中药组以益智健脑颗粒浓缩液灌胃;正常对照组和模型组以双蒸水灌胃。8周后,采用逆转录-聚合酶链反应(RT-PCR)方法检测海马组织中Pin1和HMGB1 mRNA的表达。结果:与模型组比较,中药治疗组Pin1 mRNA相对表达量上调(P<0.05);HMGB1mRNA相对表达量下调(P<0.05)。结论:益智健脑颗粒可能通过上调Pin1 mRNA表达,下调HMGB1 mRNA表达,来达到防治阿尔茨海默病的作用。

芪归健脑颗粒对老年性痴呆大鼠学习记忆及脑组织nNOS、COX-2蛋白表达的影响

目的:观察芪归健脑颗粒对老年性痴呆(AD)大鼠学习记忆能力的保护作用,并探讨其作用机制。方法:W istar雄性大鼠70只,随机分为7组,每组10只,即芪归健脑颗粒高剂量组、芪归健脑颗粒中剂量组、芪归健脑颗粒低剂量组、吡拉西坦组、模型组、假手术组与正常组,采用海马区注射Aβ-40溶液制作AD大鼠模型。各组大鼠在造模后第7天开始给药治疗,正常组、假手术组与模型组大鼠给予等容积生理盐水,连续21天。观察AD大鼠学习记忆能力,并用免疫组化法检测脑组织中氧化亚氮合酶(nNOS)和环氧化酶2(COX-2)蛋白表达的影响。结果:芪归健脑颗粒能明显缩短Aβ-40所致AD模型大鼠的潜伏期,增加穿越平台的次数,显著降低AD模型大鼠海马COX-2阳性表达,提高nNOS阳性表达。结论:芪归健脑颗粒对Aβ-40所致AD模型大鼠学习记忆障碍具有明显的改善作用,其机制可能是芪归健脑颗粒通过COX-2,nNOS等信号转导途径,减轻Aβ-40毒性作用所致脑组织神经元损伤,从而改善学习记忆障碍,起到防治AD的作用。

Modulatory effects of acupuncture on brain networks in mild cognitive impairment patients

Functional magnetic resonance imaging has been widely used to investigate the effects of acupuncture on neural activity. However, most functional magnetic resonance imaging studies have focused on acute changes in brain activation induced by acupuncture. Thus, the time course of the therapeutic effects of acupuncture remains unclear. In this study, 32 patients with amnestic mild cognitive impairment were randomly divided into two groups, where they received either Tiaoshen Yizhi acupuncture or sham acupoint acupuncture. The needles were either twirled at Tiaoshen Yizhi acupoints, including Sishencong（EX-HN1）, Yintang（EX-HN3）, Neiguan（PC6）, Taixi（KI3）, Fenglong（ST40）, and Taichong（LR3）, or at related sham acupoints at a depth of approximately 15 mm, an angle of ± 60°, and a rate of approximately 120 times per minute. Acupuncture was conducted for 4 consecutive weeks, five times per week, on weekdays. Resting-state functional magnetic resonance imaging indicated that connections between cognition-related regions such as the insula, dorsolateral prefrontal cortex, hippocampus, thalamus, inferior parietal lobule, and anterior cingulate cortex increased after acupuncture at Tiaoshen Yizhi acupoints. The insula, dorsolateral prefrontal cortex, and hippocampus acted as central brain hubs. Patients in the Tiaoshen Yizhi group exhibited improved cognitive performance after acupuncture. In the sham acupoint acupuncture group, connections between brain regions were dispersed, and we found no differences in cognitive function following the treatment. These results indicate that acupuncture at Tiaoshen Yizhi acupoints can regulate brain networks by increasing connectivity between cognition-related regions, thereby improving cognitive function in patients with mild cognitive impairment.

地黄益智方对APP/PS1双转基因小鼠海马神经元凋亡和Nrf2通路蛋白的影响

目的观察地黄益智方对APP/PS1转基因小鼠海马神经元凋亡及Nrf2/ARE通路蛋白表达的影响。方法以APP/PS1双转基因小鼠为阿尔茨海默病模型动物,给予盐酸多奈哌齐(西药组)和地黄益智方干预12周,TUNEL染色检测细胞凋亡,试剂盒检测Caspase-3活性,ELISA检测血清核因子E_(2)相关因子2(Nrf2),血红素加氧酶1(HO-1)和醌氧化还原酶1(NQO1)。结果TUNEL染色发现模型组细胞核皱缩,神经元凋亡多于正常组(P<0.001);西药组及地黄益智方各剂量组凋亡神经元均少于模型组(P<0.01)。模型组Caspase-3活性高于正常组(P<0.001),西药组及地黄益智方各剂量组Caspase-3活性较模型组降低(P<0.05)。模型组Nrf2、HO-1和NQO1蛋白表达均低于正常组,西药组及地黄益智方各剂量组Nrf2、HO-1和NQO1水平升高(P<0.05)。结论地黄益智方可以抑制APP/PS1双转基因阿尔茨海默病小鼠海马神经元凋亡,其机制可能与调控Nrf2/ARE信号通路,上调HO-1和NQO1,抑制Caspase-3活性相关。

健脾益智汤对阿尔茨海默病大鼠脑内尿素循环酶含量的调控

目的 观察健脾益智汤调控阿尔茨海默病(AD)模型大鼠的尿素循环相关酶的影响,探讨健脾益智汤改善模型大鼠脑内尿素代谢的可能机制。方法 采用SPF级雄性SD大鼠随机分为对照组、假手术组、模型组、健脾益智汤组、吡拉西坦组。采用海马区注射Aβ1-40的方法制备AD动物模型,两个给药组大鼠分别灌胃健脾益智汤和吡拉西坦7、14、28 d,随后处死取出全脑。采用ELISA法检测尿素循环相关酶精氨酸酶(ARG),精氨基琥珀酸合成酶(ASS)和精氨酸代琥珀酸裂解酶(ASL)的含量。结果 在治疗7、14、28 d时,与对照组比较,模型组脑内ARG、ASS含量均明显升高,P<0.01或P<0.05。与模型组相比,在治疗7 d时,健脾益智汤组与吡拉西坦组ARG、ASS含量有所下降;在治疗14和28 d时,健脾益智汤组与吡拉西坦组ARG、ASS含量明显下降,P<0.01或P<0.05。结论 健脾益智汤可能通过下调ARG、ASS酶活性,使尿素生成减少或降低炎症细胞因子的表达水平而达到改善学习记忆障碍的作用。

复方苁蓉益智胶囊联合奥拉西坦治疗老年阿尔茨海默病的临床疗效

目的:分析复方苁蓉益智胶囊联合奥拉西坦治疗老年阿尔茨海默病的临床疗效。方法:选取2018年1月至2021年9月北京市隆福医院收治的148例老年阿尔茨海默病患者作为研究对象,采用随机数字表法简单随机化分为对照组和观察组,每组74例。对照组采用奥拉西坦胶囊进行治疗,观察组在对照组的基础上联合复方苁蓉益智胶囊治疗,均治疗3个月。比较2组患者临床疗效、氧化应激指标、炎症介质、病情严重程度、胆碱能神经递质水平、血液流变学指标及简易精神状态量表(MMSE)评分。结果:治疗后,观察组总有效率高于对照组(P<0.05)。与治疗前比较,治疗后2组患者血清超氧化物歧化酶(SOD)、乙酰胆碱(ACh)、胆碱酯酶(AChE)水平、MMSE及画钟试验评分、即刻记忆、回忆、注意力及计算力、地点定向力、时间定向力、语言评分升高,观察组高于对照组(均P<0.05);2组患者血清丙二醛(MDA)、白细胞介素-1β(IL-1β)、核因子κB水平及临床痴呆量表(CDR)评分、全血高切黏度、全血低切黏度、红细胞聚集指数降低,观察组低于对照组(均P<0.05)。结论:复方苁蓉益智胶囊联合奥拉西坦可有效减轻老年阿尔茨海默病患者机体炎症反应和氧化应激反应,缓解患者病情进展,调节神经递质水平和血液流变学,改善其认知功能,具有较好的治疗效果。

养血清脑颗粒联合奥拉西坦治疗阿尔茨海默病临床研究

目的观察养血清脑颗粒联合奥拉西坦治疗阿尔茨海默病的临床效果。方法选取中南大学湘雅医学院附属海口医院2020年3月至2022年2月收治的阿尔茨海默病患者124例。按照随机数字表法分为对照组(奥拉西坦治疗,62例)和观察组(养血清脑颗粒联合奥拉西坦治疗,62例)。2组均持续治疗6个月。比较2组疗效,治疗前后痴呆病理行为评定表(BEHAVE-AD)、日常生活能力量表(ADL)、蒙特利尔认知评估量表(MoCA)评分、血清指标[高敏C反应蛋白(hs-CRP)、白细胞介素1β(IL-1β)、β淀粉样蛋白1-42(Aβ1-42)、Tau蛋白]水平和不良反应发生情况。结果观察组的临床总有效率高于对照组[91.9%(57/62)比77.4%(48/62)],差异有统计学意义(χ^(2)=5.035,P=0.025)。2组治疗6个月后BEHAVE-AD、ADL评分低于治疗前,MoCA评分高于治疗前,且观察组BEHAVE-AD、ADL评分低于对照组,MoCA评分高于对照组,差异均有统计学意义(均P<0.05)。2组治疗6个月后hs-CRP、IL-1β、Aβ1-42、Tau蛋白水平均低于治疗前,且观察组均低于对照组,差异均有统计学意义(均P<0.05)。观察组与对照组不良反应总发生率比较[12.9%(8/62)比11.3%(7/62)]差异无统计学意义(χ^(2)=0.076,P=0.783)。结论养血清脑颗粒联合奥拉西坦可有效改善阿尔茨海默病患者的临床症状,提高患者的认知功能和日常生活能力,调节血清hs-CRP、IL-1β、Aβ1-42、Tau蛋白水平。

补肾益智汤联合卡巴拉汀治疗阿尔兹海默症临床效果及对血清缓激肽水平的影响

目的：观察补肾益智汤联合卡巴拉汀治疗阿尔兹海默症的临床效果及对血清缓激肽水平的影响。方法：选择医院收治的70例符合入组标准的阿尔兹海默症患者作为研究对象,按随机数字表分为研究组（35例）和对照组（35例）,对照组患者给予卡巴拉汀治疗,研究组在对照组的基础上再口服补肾益智汤,4周为1个疗程,两组均治疗6个疗程,治疗前后进行中医症候积分、简易智能状态量表（mini-mantal state examination,MMSE）评分、修订韦氏记忆量表（WMS）、痴呆量表（Blessed-Roth）评分、阿尔兹海默症评定量表（ADAS-Cog）评分、日常生活能力量表（ADL）评分评判,取清晨空腹血,采用生物素双抗体夹心酶联免疫吸附法进行血清缓激肽（BK）检测,评价中医临床疗效,记录不良反应发生情况。结果：研究组治疗后记忆力减退、腰膝酸软、倦怠嗜卧、表情呆钝、善惊易恐、脑转耳鸣、面颊潮红等中医症候积分均较治疗前明显下降（P〈0.05）,而对照组仅记忆力减退明显改善（P〈0.05）。研究组和对照组治疗后MMSE、WMS明显升高（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显降低（P〈0.05）,且研究组治疗后MMSE、WMS明显高于对照组（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显低于对照组（P〈0.05）。研究组和对照组治疗后BK均明显降低（P〈0.05）,研究组治疗后BK明显低于对照组（P〈0.05）。研究组的中医临床疗效总有效率为82.86%,明显高于对照组62.86%,差异具有统计学意义（P〈0.05）。结论：阿尔兹海默症在卡巴拉汀治疗的基础上再加用补肾益智汤治疗的临床疗效明显,能有效改善患者认知功能、记忆功能、痴呆程度及日常生活能力,可能与其降低血清血清缓激肽水平有关。

益智聪明汤对Aβ25-35致阿尔茨海默病小鼠模型行为学及tau蛋白表达的影响

目的：探讨益智聪明汤对β-淀粉样蛋白（Aβ（25-35））致阿尔茨海默病模型（AD）小鼠的学习记忆改善作用及其对tau蛋白表达的影响。方法：选取60只昆明种小鼠,随机分为假手术组,模型组,益智聪明汤低、中、高剂量组及多奈哌齐组,海马内注射Aβ（25-35）后制作小鼠AD模型。各组小鼠按相应剂量灌胃给药,连续15 d,1次/d。Y迷宫和Morris水迷宫实验检测各组小鼠认知行为改变,免疫组织化学法测定tau蛋白磷酸化位点（Ser199）的影响。结果：益智聪明汤对AD模型小鼠的进臂总次数无影响,但可显著增加小鼠的自发交替反应率,缩短逃避潜伏期,减少总路程,延长游泳路程百分比;对游泳速度无影响,可减少tau蛋白磷酸化位点（Ser 199）的表达。结论：益智聪明汤课可通过抑制tau蛋白磷酸化的表达,进而对Aβ（25-35）致阿尔茨海默病模型小鼠学习记忆障碍具有改善作用。

复方益智颗粒治疗老年性痴呆有效成分的文献研究

文章主要通过文献研究的方法,对复方益智颗粒治疗老年性痴呆的有效成分进行了归纳和分析。结果表明,人参皂苷Rb_1、Rd、Re、Rg_1、Rg_2、Rg_3,能通过不同的分子机制对Aβ引起的神经细胞毒性起到抑制作用;三七皂苷R_1、R_2、R_4、R_6、Fa,也具有减轻细胞对Aβ的神经毒性反应和促进细胞突起生长的作用,对老年性痴呆的病理发展有拮抗作用;绞股蓝皂苷III、IV、Ⅻ、X、Ⅰ、A-AH,可以明显提高模型小鼠的学习记忆能力,改善海马胆碱能系统功能,对诱导Aβ的AD细胞模型具有保护作用;淫羊藿苷对Aβ_(25-35)所致神经细胞损伤具有保护作用,有利于老年性痴呆的治疗;原儿茶酸具有良好的神经保护作用;桑椹花色苷和氧化白藜芦醇都对神经系统有良好的保护作用。研究结果提示,皂苷类和黄酮类成分有可能是复方益智颗粒治疗老年性痴呆的物质基础,可为后续该制剂治疗老年性痴呆物质基础的研究奠定基础。

益智健脑颗粒水提浓缩液对P8系快速老化小鼠内嗅区组织差异蛋白质表达的影响

目的分析益智健脑颗粒水提浓缩液(Yizhi Jiannao Granule Concentration Fluid,YJGCF)干预前后P8系快速老化小鼠(senescence accelerated mouse P8,SAMP8)内嗅区组织的差异蛋白质表达,从蛋白质组学水平探讨中药益智健脑颗粒水提浓缩液治疗阿尔茨海默病(Alzheimer′s disease,AD)的作用机制。方法 6月龄SAMP8随机分为治疗组、模型组和对照组,每组10只。模型组不予处理,让其自由饮水,治疗组以YJGCF灌胃(0.3g/d),对照组以等剂量双蒸水灌胃。8周后、应用双向凝胶电泳技术分别分离3组SAMP8内嗅区组织总蛋白,得到差异蛋白质点,通过质谱分析得到相应肽质量指纹图谱,经蛋白质数据库查询,鉴定差异蛋白质点。结果治疗组与模型组存在32个差异点,初步鉴定了NADH脱氢酶铁硫蛋白6、Rho-GDP解离抑制因子α、β2珠蛋白、磷酸甘油酸激酶等14个差异蛋白质,其功能涉及线粒体能量代谢、氧化应激、神经元功能等方面。结论 YJGCF可调节SAMP8内嗅区组织的多种蛋白质表达,提示该药具有多靶点治疗的作用,且可能通过改善线粒体功能障碍、抗氧化应激、抑制神经细胞凋亡、保护神经元等途径来实现其治疗AD的作用。

补肾益智方治疗老年性痴呆模型大鼠的行为学测试

目的 :探讨补肾益智方对老年性痴呆 (AD)模型大鼠神经行为学的改善作用。方法 :用Mor ris水迷宫 (MWM )技术对青年组、老年正常组 (简称老年组 )、AD模型组 (简称模型组 )、石杉碱甲 (HupA)组和补肾益智方治疗组 (简称治疗组 )进行行为学测试。结果 :治疗组平均逃避潜伏期 (EL)变化曲线位于青年组、老年组和模型组、HupA组之间 ;中环游泳路程百分比、4 0cm环游泳时间、跨平台次数治疗组与老年组比较差异无显著性 ,与模型组比较差异有显著性 (P <0 0 5)。结论

补肾益智颗粒联合西药治疗阿尔茨海默病的临床观察

目的观察补肾益智颗粒联合西药治疗阿尔茨海默病(AD)的临床疗效。方法将100例AD患者随机分为观察组和对照组,观察组服用补肾益智颗粒和西药治疗,对照组单纯服用西药治疗。两组分别在治疗前后进行中医症状积分,AD评估量表-认知部分(ADAS-cog)、简易智能状态检查表(MMSE)和日常生活能力量表评分(ADL)。结果观察组治疗后临床疗效优于对照组(P<0.05);观察组治疗后中医症状积分、ADAS-cog及ADL量表积分较治疗前显著降低(P<0.05),MMSE积分较治疗前显著升高(P<0.05)。结论补肾益智颗粒联合西药治疗AD,可以显著改善AD患者的总体功能、认知障碍及日常生活能力,疗效优于单纯服用西药组。