OBJECTIVE: To explore the mechanism of action of Xixin decoction(XXD) for the prevention and treatment of sporadic Alzheimer disease(SAD) by investigating the effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein. METHODS: Specific pathogen-free(SPF) male Sprague-Dawley(SD) rats with SAD were randomly divided into six groups: sham-operated, model(intracerebroventricular injection of Streptozotocin, ICV-STZ), donepezil(0.92 mg/kg), XXD low-dose(7.61 g/kg-1 ·d-1), moderate-dose(15.21 g/kg-1 ·d-1), and high-dose(30.42 g/kg-1 ·d-1). Immunohistochemistry and western immunoblotting were used to detect the phosphorylation at Thr231 and Ser422 sites of tau protein. RESULTS: XXD different dose groups decreased to varying degrees the expression of phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocam-pus of SAD rats. No significant difference was found between the donepezil and model group. CONCLUSION: XXD may prevent SAD pathological progress by inhibiting hyperphosphorylation at the key sites of tau proteins.
OBJECTIVE:To investigate the neuroprotective mechanism of combination extract of Renshen(Panax Ginseng),Yinyanghuo(Herba Epimedii Brevicornus),Yuanzhi(Radix Palygalae) and Jianghuang(Rhizoma Curcumae Longae)(GEPT) in treating Alzheimer's disease on the target of glycogen synthase kinase 3β(GSK-3β).METHODS:Three-month-old APPV717I transgenic mice were randomly divided into ten groups(n=12 per group) and intragastrically administrated vehicle or medicines:APP group was given 0.5% CMC,donepezil group was given donepezil(APP + D group)(0.92 mg/kg-1·day-1),and GEPT groups were given small dose of GEPT(APP+Gs group)(0.075 g/kg-1·day-1),medium dose(APP+Gm group)(0.15 g/kg-1·day-1),and large dose(APP+Gl group)(0.30 g/kg-1·day-1) for 4 or 8 months,respectively.Three-month-old C57BL/6J mice as vehicle controls(n=12) were given 0.5% CMC for 4 or 8 months as well.The GSK-3β expression in the cortex of 7-and 11-month-old APPV717I transgenic mice with and without GEPT or donepezil treatment and normal C57BL/6J mice were measured via Western blotting and Immunohistochemistry.RESULTS:Immunohistochemistry analysis showed significant increase of GSK-3β in the cerebral cortex of 7-month-old APP group(compare to control group P=0.003),while the GSK-3β expression of donepezil or GEPT group were all significantly decreased(Donepezil vs APP:P=0.041;Gl vs APP:P= 0.049;Gm vs APP:P=0.029;Gh vs APP:P=0.036).Western blot analysis showed similar results.The densitometric measures of GSK-3β in APP mice increased significantly as compared with the control group(P=0.008).And the GSK-3β expression in donepezil and GEPT groups were all decreased.There was significant difference between Gh group or donepezil group and the control group(P=0.05).Similar findings were shown in the 11-month-old mice in each group,except for greater decrease of GSK-3β in the GEPT group.CONCLUSION:GEPT can effectively decrease the level of GSK-3β expression in the brain cortex of APPV717I transgenic mice,and such effect is more significant in 11-month-old m
Jing ShiJinzhou TianXuekai ZhangChuiyou ZengMingqing WeiPengwen WangYongyan Wang
OBJECTIVE: To study the effects of Xixin decoction (XXD) on O-linked N-acetylglucosamine (O-GlcNAc) glycosylation of tau proteins in rat brain with sporadic Alzheimer disease (SAD), and discuss its possible mechanism on prevention and treatment of SAD. METHODS: The rat model of SAD was established by intracerebroventricular injection of streptozotocin. The specific pathogen free male Sprague-Dawley rats were randomly divided into sham-operation group (S), model group (M), donepezil group (D), XXD at a low dose group (XL), XXD at a medium dose group (XM) and XXD at a high dose group (XH). After treatment and praxiology test, immuno-histochemistry and western blotting were used to detect O-GlcNAc glycosylation level of tau proteins in rat brain with SAD. O-GlcNAc glycosylation and expression of tau proteins were detected by O-GlcNAc-specific antibodies RL2 and CTD110.6. RESULTS: O-GlcNAc glycosylated proteins enriched by succinylated wheat germ agglutinin significantly improved in the hippocampus of SAD rats. Thedifferences were statistically significant among XXD groups (P<0.05, P<0.01), while no obvious differences were observed between D group and M group (P>0.05). CONCLUSION: XXD can significantly improve O-GlcNAc glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe inhibit hyperphosphorylation of tau proteins on key sites and its toxicity, and prevent the pathological process of SAD.
背景:血管性痴呆是继阿尔茨海默病后的第二大常见痴呆类型。随着人口的老龄化,其患病率逐步上升。但目前尚无证实有效的药物,因此寻求中医治疗是非常必要的。瘀阻脑络证是血管性痴呆的主要中医证候。目的:观察活血化瘀中药治疗轻中度血管性痴呆的临床疗效及安全性。设计、场所、对象和干预措施:这是一项随机、双盲、安慰剂平行对照临床试验。自2009年3月至2010年12月共纳入48例轻中度血管性痴呆患者,随机分为活血化瘀中药组(n=24)和安慰剂对照组(n=24),所有患者接受2周的洗脱期,其后分别接受为期12周的活血化瘀中药治疗或安慰剂。安慰剂气味和外观均与活血化瘀中药相同。主要结局指标:主要疗效指标是阿尔茨海默病评估量表(认知部分)(Alzheimer's Disease Assessment Scale-cognitive subscale,ADAS-cog);次要疗效指标是简易精神状态检查量表(Mini-Mental State Examination,MMSE)和日常生活能力量表(Activities of Daily Living,ADL)。结果:基线时两组人口学及神经心理学量表得分均无差异。活血化瘀中药组治疗12周后ADAS-cog得分较基线无显著变化(P>0.05),安慰剂组12周后ADAS-cog得分较基线显著升高2.35分,两组间ADAS-cog变化值的差异具有统计学意义(P=0.027)。两组间MMSE和ADL得分与基线比较差异无统计学意义。两组间不良反应的发生率均较低,且两组间差异无统计学意义。结论:活血化瘀中药能维持患者认知功能,并且具有良好的安全性和耐受性,其远期疗效及安全性尚需大样本临床研究证实。
