Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Polygala tenuifolia and Acorus tatarinowii in the treatment of Alzheimer's disease: a systematic review and meta-analysis.

Background: The complexity of Chinese medicine treatment for Alzheimer's disease (AD) utilizing a multi-herb therapy makes the evidence in current studies insufficient. Herb pairs are the most fundamental form of multi-herb formulae. Among the Chinese herbal formulas for AD treatment, Polygala tenuifolia (PT) and Acorus tatarinowii (AT) appeared as the most commonly used herbal pairs in combination. Objective: The aim of this study is to evaluate the clinical efficacy and safety of the combination of PT and AT in the treatment of AD. Methods: We systematically searched and screened randomized controlled trials of pairing PT and AT for the treatment of AD patients in eight databases with a search deadline of June 26, 2023. Authors, year of publication, title, and basic information such as subject characteristics (age, sex, and race), course of disease, control interventions, dose, and treatment duration were extracted from the screened studies. Primary outcomes assessed included mini-mental state examination (MMSE), activities of daily living (ADL), and AD assessment scale-cognitive subscale (ADAS-cog), while secondary outcomes included efficiency and adverse events. The quality of the included studies was assessed using the Cochrane risk of bias tool. The mean difference with 95% confidence intervals (MD [95% CI]) and risk ratio (RR) was selected as the effect size, and the data were analyzed and evaluated using RevMan 5.4 and Stata 16. Results: A total of sixteen eligible and relevant studies involving 1103 AD participants were included. The combination of PT and AT plus conventional drugs was superior to single conventional drugs in MMSE [MD = 2.57, 95%CI: (1.44, 3.69); p < 0.00001; I 2 = 86%], ADL [MD = -3.19, 95%CI: (-4.29, -2.09); p < 0.00001; I 2 = 0%], and ADAS-cog scores [MD = -2.09, 95%CI: (-3.07, -1.10); p < 0.0001; I 2 = 0%]. The combination of PT and AT plus conventional drugs had a significantly more favorable benefit in clinical effectiveness [RR = 1.27, 95%CI: (1.12, 1.44); p = 0.0002; I 2 = 0%]. Adverse events were not increased with the combination of PT and AT plus conventional drugs compared to conventional drugs [RR = 0.65, 95%CI: (0.35, 1.19); p = 0.16; I 2 = 0%]. The experimental group treated with the combination of PT and AT alone for AD was comparable in MMSE, ADL, and ADAS-cog scores compared with the control group treated with single conventional drugs. Conclusion: Compared to single conventional drugs, the combination of PT and AT may be used as an alternative therapy to improve global cognition and functioning in AD, and the combination of PT and AT as adjunctive therapy appears to produce a better therapeutic response to AD in terms of efficacy without increasing the risk of adverse events. However, the very low to low quality of available evidence limits confidence in the findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023444156.

External therapy of Chinese medicine for postherpetic neuralgia: A protocol for systematic review and meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN), the most common complication of herpes zoster, brings about a health-care burden at both the individual and societal levels. External therapy of Chinese medicine (ETCM) is an effective treatment of PHN generally available in China, yet there is incomplete evidence to evaluate the efficacy and safety of it. METHODS: This protocol is based on the previous reporting items. We will search 3 English databases (PubMed, EMBASE, and the Cochrane Library) and 3 Chinese databases (CNKI, CBM, and Wan Fang Database) until January 2020. RCTs to evaluate the efficacy and safety of external therapy of Chinese medicine for postherpetic neuralgia will be included. The primary outcome will be assessed by VAS or NRS. We will use the criteria provided by Cochrane Handbook 5.3.0 for quality evaluation and risk assessment, and use the Revman 5.3 software for meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42020163511.

GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine.

BACKGROUND: Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. METHODS: Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC-MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step-down passive-avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T-SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. RESULTS: After one-half or 1 month of intragastric administration, GAPT can ameliorate scopolamine-induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine-treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. CONCLUSIONS: GAPT can improve the learning and memory ability of scopolamine-induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial.

BACKGROUND AND PURPOSE: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT). METHODS: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus). RESULTS: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found. CONCLUSIONS: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

Chinese herbal medicine Qinggongshoutao for the treatment of amnestic mild cognitive impairment: A 52-week randomized controlled trial.

INTRODUCTION: This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). METHODS: Patients with aMCI were randomly assigned to receive QGST, Ginkgo biloba extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale-cognitive subscale scores; secondary outcome measures included assessments for cognition and function. RESULTS: Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale-cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. DISCUSSION: In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.

Sequential Therapy Based on Evolvement of Patterns: A New Model for Treatment of Alzheimer's Disease.

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.

Effect of Chinese herbal compound GAPT on the early brain glucose metabolism of APP/PS1 transgenic mice.

A number of studies have shown that early-stage Alzheimer's disease (AD) is associated with abnormal brain glucose metabolism before cognitive decline, which may be the key pathological change of asymptomatic AD. The pathogenesis of AD in traditional Chinese medicine is kidney deficiency and turbid phlegm. Based on this, GAPT (a mixture of herbal extracts) was made to invigorate kidney Yang and eliminate phlegm. Previous studies have shown that GAPT can improve and delay the memory decline, but the specific therapeutic target of AD in an early stage has not been studied. The aim of this study was to investigate the effect of GAPT on glucose metabolism in the early stage of AD. Eighty-eight 3-month-old male APP/PS1 transgenic mice were randomly divided into model group; donepezil group; and low, middle and high GAPT dosage groups. Twelve 3-month-old C57BL/6J mice were used as a control group. The Morris water maze test and the Step-Down Passive-Avoidance test were used to evaluate learning and memory ability. Cerebral extraction and the accumulation of glucose were scanned with a micro-positron-emission tomography (PET) imaging system. Immunohistochemistry, western blot analysis and polymerase chain reaction (PCR) were used to detect the expression of the PI3K/AKT-mTOR signalling pathway-related proteins and messenger RNAs (mRNAs) in hippocampus of APP/PS1 transgenic mice after 3 months of drug administration. GAPT can shorten the escape latency and error numbers compared to the model group. In micro-PET imaging analysis, GAPT can increase the glucose uptake average rate in the frontal lobe, temporal lobe, parietal lobe and hippocampus. The immunohistochemistry, western blot analysis and PCR results indicated that GAPT can increase the expression of PI3K, AKT, GLUT1 and GLUT3 in the hippocampus of APP/PS1 transgenic mice. In summary, GAPT can improve brain glucose metabolism damage in APP/PS1 transgenic mice, mainly by increasing brain glucose uptake, increasing glucose transport and improving the insulin signalling pathway.

Efficacy and safety of Tianmabianchunzhigan in mild to moderate vascular dementia: Protocol of a randomized controlled IIa trial.

BACKGROUND: Vascular dementia (VaD) is the 2nd most common subtype of dementia after Alzheimer disease. Currently, there are no medications approved for treating patients with VaD. Tianmabianchunzhigan (TMBCZG) tablet is an active ingredient extracted from Gastrodia that has been reported to improve memory and other cognition. And the TBMCZG has been approved clinical trial with patients with VaD by center for drug evaluation of China (CFDA). To evaluate the efficacy, safety, and tolerability of TMBCZG tablets in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week, randomized, double-blind, parallel, placebo-controlled, multicenter trial. METHODS: A total of 160 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either TMBCZG high-dose group (TBMCZG 3 tablets, twice per day); TMBCZG middle-dose group (TMBCZG 2 tablets and placebo 1 tablet twice per day); TMBCZG low-dose group (TMBCZG 1 tablet and placebo 2 tablets, twice per day); placebo group (placebo 3 tablets, twice per day) for 24 weeks, with a follow-up 12 weeks after withdrawn drug treatment. The primary efficacy measurement will be the vascular dementia assessment scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes scale. The secondary efficacy measurements will include the mini mental state examination and activities of daily living. Adverse events will also be reported. DISCUSSION: This randomized trial will be the 1st rigorous study on the efficacy and safety of TMBCZG tablets for treating cognitive symptoms in patients with VaD using a rational design. TRIAL REGISTRATION: ClinicalTrials.gov NCT03230071. Registered on July 26, 2017.

Banxia Xiexin decoction ameliorated cognition via the regulation of insulin pathways and glucose transporters in the hippocampus of APPswe/PS1dE9 mice.

Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer's disease correlate with impaired cognition, and this information is evidence that Alzheimer's disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice. We used 3-month-old APPswe/PS1dE9 double transgenic mice as the case groups and wild-type littermates of the double transgenic mice from the same colony as the control group. Forty-five APPswe/PS1dE9 double transgenic mice were randomly divided into the model group, donepezil group and BXD group. The mice in the control and model groups were administered 0.5% carboxymethyl cellulose orally. The Morris water maze and step-down test were conducted to evaluate the cognitive performance of APPswe/PS1dE9 double transgenic mice after BXD treatment. Ultrastructure of synapses was observed in the hippocampal CA1 area. Proteins involved in insulin signalling pathways and glucose transports in the hippocampus were assessed through immunohistochemical staining and western blot. After 3 months intervention, we found that BXD treatment improved cognitive performance and the synaptic quantity and ultrastructure, restored insulin signalling and increased the expression of glucose transporter 1 (GLUT1) and GLUT3 levels. These findings suggest that the beneficial effect of BXD on cognition may be due to the improvement of insulin signalling, glucose metabolism and synaptic plasticity.

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer's disease: a retrospective analysis.

BACKGROUND: Conventional therapy (CT) such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer's disease (AD). The efficacy of them, however, drops below baseline level after 9 months. In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy combined with herbal therapy (CT + H) make add-on benefit? METHODS: In this retrospective cohort study, 344 outpatients diagnosed as probable dementia due to AD were collected, with the treatment of either CT + H or CT alone in clinical settings. All the patients were examined with coronary MRI scan. Cognitive functions were obtained by mini-mental state examination (MMSE) every 3 months with the longest follow-up of 24 months. RESULTS: Most of the patients were initially diagnosed with mild (MMSE = 21-26, n = 177) and moderate (MMSE = 10-20, n = 137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P = 0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P < 0.001) better. At 24 months, the patients with improved cognitive function (△MMSE ≥ 0) in CT + H was more than CT alone (33.33% vs 7.69%, P = 0.020). Interestingly, patients with mild AD received the most robust benefit from CT + H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE = -0.06), a significant improvement from CT alone (ΔMMSE = -2.66, P = 0.005). CONCLUSIONS: Compared to CT alone, CT + H significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Effect of GAPT extract on expression of tau protein and its phosphorylation related enzymes in hippocampal neurons of APPV717I transgenic mice.

OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg•d)], the low, medium and high dosage of GAPT groups [0.075, 0.15, 0.30 g/(kg•d), 12 in each group], and 12 three-month-old C57BL/6J mice were set as a normal control group, treatments were administered orally once a day respectively, and both the normal group and model group were given 0.5% sodium carboxymethyl cellulose solution. Immunohistochemistry (IHC) and Western blot analysis were used to detect the expression of total tau protein (Tau-5), cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in hippocampal neurons of experimental mice after 8-month drug administration (11 months old). RESULTS: In the model group, the expression of Tau-5 and CDK5 were increased, whereas the expression of PP2A was decreased in hippocampal neurons, which were signifificantly different compared with that in the normal group (all P<0.01). IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups, and an increase of PP2A. Compared with the model group, the changes were signifificant in GAPT groups (P<0.05 or P<0.01). Similar results were shown by Western blot. CONCLUSION: GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.

Efficacy and Safety of an Herbal Therapy in Patients with Amnestic Mild Cognitive Impairment: A 24-Week Randomized Phase III Trial.

OBJECTIVE: In the 24-week randomized, double-blind, double-placebo, parallel-controlled trial, we aimed to test the effects of herbal therapy with amnestic mild cognitive impairment (aMCI). METHODS: A total of 324 patients with aMCI entered a 2-week placebo run-in period followed by 24 weeks' treatment of either (a) herbal capsule (5 shenwu capsules/administration, 3 times/day) and placebo identical to donepezil tablets (n = 216) or (b) donepezil (5 mg/day) and placebo identical to herbal capsule (n = 108). RESULTS: Herbal therapy showed a significant improvement on the primary efficacy measure, measured by Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), and showed a mean decrease from baseline of 4.23 points at the endpoint, without a significant difference from the donepezil group. Secondary efficacy measurement of the Logical Memory II Delayed Story Recall subtest (DSR) showed modest improvement in those taking herbal capsule compared to baseline, and there was no significant difference from donepezil group. The frequency of adverse events was much less in the herbal therapy group than the donepezil. CONCLUSION: Herbal therapy demonstrated a significant improvement in cognition and memory, which were similar to the donepezil in patients with aMCI. Herbal therapy was safe and well tolerated. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov NCT01451749.

Efficacy and safety of SQJZ herbal mixtures on nonmotor symptoms in Parkinson disease patients: Protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: As a multisystemic neurodegenerative disorder, Parkinson disease (PD) has a broad spectrum of symptoms including motor and nonmotor symptoms (NMS). As shown in studies, NMS can also impact patient's quality of life, and many of them often go untreated. Chinese herbal medicines with multiconstituent may alleviate NMS in PD patients. This research is carried out to assess the efficacy and safety of a Chinese herbal formula for NMS, with its Chinese name acronym of SQJZ. METHODS/DESIGN: It will be a multicenter, randomized, double-blind, placebo-controlled trial. Idiopathic PD with a Hoehn and Yahr scale score ≤4, aged 18 to 80 years, will be involved. About 240 patients will be randomly assigned to either SQJZ or placebo in a 2:1 ratio. There is a 2-week run-in period before the randomization, and the follow-up will be 24 weeks, including 12-week treatment period, with visit once every 4 weeks and 12-week washout follow-up. All participants are asked to maintain the regular medication schedule. SQJZ formula will consist of Chinese herbs with effects for insomnia, constipation, anxiety, and so on. The primary outcome will be measured using NMS scale, and secondary outcomes will include unified PD rating scale, PD sleep scale, the Parkinson fatigue scale, the constipation severity instrument, and PD Questionnaire-39. The primary efficacy analysis will be based on the intention-to-treat method, and mixed-model repeated-measures analyses will be used. DISCUSSION: The findings from this research might provide evidence of the efficacy and safety of SQJZ Chinese herbal formula for treating NMS in PD patients. The results will sustain the broader use of SQJZ formula in PD.

Herbal formula GAPT prevents beta amyloid deposition induced Ca(2+)/Calmodulin-dependent protein kinase II and Ca(2+)/Calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice.

BACKGROUND: Synaptic dysfunction is one of the pathological characteristics of Alzheimer's disease (AD), which is directly related to the progressive decline of cognitive function. CaMKII and CaN have been found to play important roles in memory processes and synaptic transmission. So present study aimed to elucidate relationships between CaMKII, CaN and cognitive decline in APPV717I mice, and to reveal whether the cognitive improving effects of GAPT is conducted through rebalance CaMKII and CaN. METHODS: Three-month-old-male APPV717I mice were randomly divided into ten groups (n = 12 per group) and received intragastrically administrated vehicle, donepezil or different doses of herbal formula GAPT for 8 or 4 months. Three-month-old male C57BL/6 J mice was set as vehicle control. RESULTS: Immunohistochemistry analysis showed that there were CaMKII expression decrease in the CA1 region of APPV717I transgenic mice, while the CaMKII expression of donepezil or GAPT treated transgenic mice were all increased. And there were CaN expression increase in the brain cortex of APPV717I transgenic mice, while there were decrease of CaN expression in donepezil or GAPT treated transgenic group. Western blot analysis showed the similar expression pattern without significant difference. CONCLUSION: GAPT extract have showed effectiveness in activating the expression of CaMKII and inhibiting the expression of CaN either before or after the formation of amyloid plaques in the brain of APPV717I transgenic mice, which may in certain way alleviated neuron synaptic dysfunction in AD.

The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.

BACKGROUND: Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. METHODS/DESIGN: This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. DISCUSSION: This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.

Ginseng for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is no curative treatment for Alzheimer's disease (AD). Ginseng is widely used in the treatment of AD in Asian countries. OBJECTIVE: To evaluate the effectiveness and safety of ginseng for AD. METHODS: We searched seven main databases for randomized clinical trials (RCTs) on ginseng for AD from their inception to December 2014. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.2 to synthesize the results. RESULTS: Four RCTs involving 259 participants were identified for this systematic review. The methodological quality of included studies was not promising. All comparisons were made between combined treatment (ginseng plus conventional treatment) versus conventional treatment. The results of meta-analyses and several individual studies showed that the effectiveness of combined treatment was inconsistent as measured by MMSE, ADAS-cog, ADAS-noncog, and CDR. No studies reported the outcomes of quality of life (QoL). The current data did not report serious adverse events. CONCLUSION: This review showed that the effects of ginseng on AD were still inconclusive. The main limitations of the available studies were small sample sizes, poor methodological qualities and no placebo controls. Larger, well-designed studies are needed to test the effect of ginseng on AD in the future.