Role of aerobic glycolysis in alzheimer's disease and research progress of traditional Chinese medicine

Alzheimer's disease (AD) is an irreversible neurodegenerative disease with a variety of pathogenic factors and complex pathogenesis, so that the disease has a high prevalence and mortality in the world. Although the current diagnosis and treatment equipment and drug research and development keep pace with the times, the current medical technology still can not completely cure the disease, so it is of great significance to explore the pathogenesis and treatment target of AD. The disorder of energy metabolism is one of the characteristic changes in the pathological process of AD. Aerobic glycolysis (AEG) is a special metabolic pathway in the brain, which can rapidly consume glucose to produce energy and substrate for neurons, improve synaptic plasticity, neuroinflammation and oxidative damage, and contribute to the recovery of memory and cognitive function. In recent years, many literatures have reported the mechanism of AEG in AD and the intervention of Tradit Chin Med on this mechanism. The purpose of this paper is to summarize the role of AEG in AD and the related research on the regulation and control of AEG in the treatment of AD by Tradit Chin Med, in order to provide reference and ideas for the prevention and treatment of AD with Tradit Chin Med in the future.

Systematic evaluation of traditional Chinese medicine for treating Parkinson's disease

BACKGROUND：To evaluate the quality of the literature addressing traditional Chinese medicine for treating Parkinson＇s disease.DATA SOURCE：A computer-based online search of Chinese publications from January 2001 to July 2008 was conducted in Chinese Biology Medical Disc Database and China National Knowledge Infrastructure. Search key words were Parkinson＇s disease, integrated traditional Chinese and Western medicine, traditional Chinese medicine therapy, and Chinese herb therapy.DATA SELECTION：Articles describing randomized, controlled trials and quasi-randomized, controlled trials were included. Literature quality was assessed using the criteria-Systematic evaluation of clinical literature related to treatment of Parkinson＇s disease with traditional Chinese medicine. This included methodology, interventions in the treatment/control group, evaluation criterion of outcomes, and frequency.MAIN OUTCOME MEASURES：Evaluation criterion of outcomes （various score methods and evaluation scales）, methodological quality, and frequency distribution were all measured.RESULTS：A total of 33 articles with randomized, controlled trials were included. Of these, six described a random method, and the remaining did not describe random allocation methods or random sequence generation methods. None of the studies estimated sample size. Case descriptions of withdrawal and loss to follow-up were unclear. Both the Unified Parkinson＇s Disease Rating Scale and Webster scale were used in the eligible studies as evaluation criteria.CONCLUSION：There are no high-quality studies that address traditional Chinese medicine therapy and integrated traditional Chinese and Western medicine for treating Parkinson＇s disease in China. Eligible studies were not performed in accordance with Consolidated Standards of Reporting Trials statement or Standards for Reporting Interventions in Controlled Trials of Acupuncture criteria, and the literature quality was low. The presently used criteria for evaluating therapeutic effects do not completely assess outcomes of traditional Chinese medicine for treating Parkinson＇s disease. The identification of precise outcomes should be verified using randomized, controlled studies with adequate controls and proper designs.

The Potential Targets of Chinese Medicines in the Treatment of Parkinson＇s Disease： Old Wine in New Bottles

This article systematically reviews the present research situation of the pathogenesis of PD （Parkinson＇s disease） and our recent research over the past decade, to discuss the potential targets of many TCM （traditional Chinese medicines） in prevention and treatment of PD, such as against oxidative stress （Astragaloside, protocatechuic aldehyde, Liu-Wei-Di-Huang）, anti-apoptosis （Geniposide, Zhichan powder）, improve mitochondrial function （Paeoniflorin, Da-Bu-Yin-Wan）, inhibition of protein aggregation （Panax ginseng, Irisflorentin）, induce autophagy （piperine, Paeoniflorin）, and many other mechanisms and multiple effectiveness （Saponins, Acanthopanax）. With the research and development in PD pathogenesis and clarifying the targets of a variety of traditional Chinese medicine, especially its monomeric components, the development of traditional Chinese medicine in prevention and treatment of PD will have very broad application value and prospect.

Research advances in the treatment of Alzheimer＇s disease with polysaccharides from traditional Chinese medicine

Alzheimer's disease(AD) is a neurodegenerative disorder characterized by the loss of patients' memory and their cognitive abilities and the mechanism is not completely clear. Although a variety of drugs have been approved for the AD treatment, substances which can prevent and cure AD are still in great need. The effect of polysaccharides from traditional Chinese medicine(TCM) on anti-AD has gained great progress and attained more and more attention in recent years. In this review, research advances in TCM-polysaccharides on AD made in this decade are summarized.

Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease

Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide （Ap）-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer＇s disease, we established a rat model of AIzheimer＇s disease by injecting A325-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer＇s disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while EIIman method showed significant decrease in the activity of acetylcholinesterase in all three regions （prefrontal cortex, medial septum and hippocampus）. These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer＇s disease.

Cellular and molecular mechanisms underlying the action of ginsenoside Rg1 against Alzheimer’s disease

Ginsenoside Rgl inhibits oxidation, aging and ce this study, we pretreated rat brain tissue sections I apoptosis, and improves cognitive function. In with ginsenoside Rgl, and established brain slice models of Alzheimer＇s disease induced by okadaic acid. The results revealed that ginsenoside Rgl pretreatment suppressed the increase in phosphorylated Tau protein expression induced by incubation with okadaic acid, and reduced brain-derived neurotrophic factor expression. These results suggest that ginsenoside Rgl upregulates brain-derived neurotrophic factor expression and inhibits Tau protein phosphorylation in brain slices from a rat model of Alzheimer＇s disease.

How do Chinese medicines that tonify the kidney inhibit dopaminergic neuron apoptosis?

Wistar rats were intragastrical y perfused with Chinese medicines used for tonifying the kidney. These included 0.180 g/mL of Herba Epimedi （Epimedium）, Semen Cuscutae （Dodder Seed）, or Herba Cistanches （Desertliving Cistanche）, 0.04 mg/mL monoamine oxidase-B inhibitor selegiline, or distil ed water for 14 consecutive days to prepare drug-containing serum or blank serum. MES23.5 cells in the logarithmic phase were cultured in media supplemented with 15%drug-containing serum for 24 hours, fol owed by incubation in culture solution containing 100μmol/L H2O2 for 3 hours. 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and flow tometry results showed that al drug-containing serums improved the survival rate of H 2 O 2-injured MES23.5 cells, inhibited pro-apoptotic FasL and caspase-3 expression, promoted anti-apoptotic Bcl-2 expression. However, drug-containing serums had little influence on Fas expression in H 2 O 2-injured MES23.5 cells. Enzyme-linked immunosorbent assay results showed that serum containing Herba Cistanches or Herba Epimedi increased the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cellline-derived neurotrophic factor in injured MES23.5 cells;serum containing Semen Cuscutae only increased brain-derived neurotrophic factor expres-sion; while expression of the above neurotrophic factors remained the same in cells treated with serum containing selegiline. These findings indicate that Chinese medicines used to tonify the kid-ney can protect nerve cells by regulating the expression of apoptosis-related factors and neuro-trophic factors in MES23.5 cells.

Compound Danshen tablets downregulate amyloid protein precursor mRNA expression in a transgenic cell model of Alzheimer's disease Effects and a comparison with donepezil

After gene mutation, the pcDNA3.1/APP595/596 plasmid was transfected into HEK293 cells to establish a cell model of Alzheimer＇s disease. The cell model was treated with donepezil or compound Danshen tablets after culture for 72 hours. Reverse transcription-PCR showed that the mRNA expression of amyloid protein precursor decreased in all groups following culture for 24 hours, and that there was no significant difference in the amount of decrease between donepezil and compound Danshen tablets. Our results suggest that compound Danshen tablets can reduce expression of the mRNA for amyloid protein precursor in a transgenic cell model of Alzheimer＇s disease, with similar effects to donepezil.

Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer＇s disease

The principal pathology of Alzheimer＇s disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques, which in turn induce neuroinflammation in the brain. Triptolide, a natural extract from the vine-like herb Tripterygium wilfordii Hook F, has potent anti-inflammatory and immunosuppressive efficacy. Therefore, we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer＇s disease. We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice （aged 4-4.5 months） for 45 days. Unbiased stereology analysis found that triptolide dose-dependent- ly reduced the total number of microglial cells, and transformed microglial cells into the resting state. Further, triptolide （5 μg/kg/d） also reduced the total number of hippocampal astrocytes. Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS 1 double transgenic mice with Alzheimer＇s disease.

Effect of Daicong solution on hippocampal muscarinic receptors 1 and 3 gene expression in a rat model of Alzheimer’s disease

BACKGROUND： It has been previously shown that the muscarinic （M） receptor is involved in brain arousal and selective attention, mood, and motor coordination. OBJECTIVE： To explore the effects of various intragastric Daicong doses on hippocampal MI and M3 receptor gene expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A randomized cellular and molecular biology experiment, conducted at the Molecular Immunology Laboratory in Shandong between October 2006 and April 2007. MATERIALS： Fifty 22-month old Sprague Dawley rats, weighing 250-300 g were used for this experiment. Kainic acid was used to lesion the nucleus basalis to establish a rat model of Alzheimer＇s disease. The components of Daicong solution were as follows： ginseng, rehmannia dride rhizome, anemarrhena, and radix astragali. The solution was provided by the Affiliated Hospital to Weifang Medical College, according to preparation techniques of extracting liquid for traditional Chinese medicine （1 g crude drug/mL solution）. Kainic acid was provided by Professor Xiuyan Li at Weifang Medical College. METHODS： The rats were randomly divided into 5 groups, 10 rats in each group. Four groups were used for model establishment, and the fifth group served as a normal control group. Three of the model groups were intragastrically administered 5, 10, and 20 g/kg/d Daicong solution, and an additional model group and normal control group received normal saline （10 mL/kg/d）. Drugs were administered over a time period of one month. MAIN OUTCOME MEASURES： Four days after model establishment, Morris water maze was used to measure learning and memory capabilities. RT-PCR was used to detect the effect of Daicong solution on mRNA expression of M1 and M3 receptor in the hippocampus of all groups. RESULTS： Fifty rats were included in the final analysis, without any loss. M1 and M3 receptor mRNA expression was decreased in the model group, compared to the normal control group （P 〈 0.05）. Upon Daicong administration （10 g/kg/d and 20 g/kg/d）, M1 and M3 receptor mRNA expression significantly increased in the hippocampus, compared to the model group （P 〈 0.05）. M1 and M3 mRNA expression was greatest in the 10 g/kg/d group. CONCLUSION： A 10 g/kg/d solution of Daicong can improve M1 and M3 receptor mRNA expression in the hippocampus of a rat model of Alzheimer＇s disease.

Progress on the Pathogenesis and Treatment of Alzheimer’s Disease

Background: Alzheimer’s disease (AD), commonly known as senile dementia, is a neurodegenerative disease with clinical manifestations of memory impairment, personality and behavior changes. The pathogenesis of AD is complex and inconclusive in the point of view of western medicine, which is the fundamental reason for the lack of drugs that can reverse the course of the disease. People have gradually shifted from simple amyloid hypothesis to new pathogenesis theories, such as gamma oscillation, prion like transmission, and so on. As an effective means to treat AD, traditional Chinese medicine has made some research progress in recent years. This article mainly reviews the etiology, pathogenesis and treatment of AD, so as to provide reference for the prevention and treatment of AD. Methods: Through systematic literature research, comparison and analysis, the main pathogenesis, influencing factors, progress and development tendency of traditional Chinese medicine and Western medicine in the treatment of AD are presented. Results: Alzheimer’s disease is a kind of multiple neurodegenerative diseases. The pathogenesis and related targets of AD still need to be further explored. The main pathological phenomenon of AD is senile plaques formed by intracellular neurofibrillary tangles and extracellular amyloid protein aggregation. Existing possible pathogenesis includes β-amyloid cascade hypothesis, tau protein hypothesis, cholinergic hypothesis and so on. As the pathogenesis of AD has not been clarified, so far no effective therapeutic drugs or means have been found. The traditional drugs used to treat AD mainly include acetylcholinesterase inhibitor kabbalatin, galantamine, donepezil, and N-methyl-D-aspartate receptor antagonist memantine. However, although these marketed drugs can slow down the course of the disease and alleviate symptoms, they cannot totally cure the disease. Traditional Chinese medicine has the characteristics of personalized differentiation and treatment. The Western medicine can accurately determine the lesion location and target. Conclusions: Integrated traditional Chinese medicine and West medicine is the most promising direction in the treatment of Alzheimer’s disease.

Traditional Chinese medicine: a promising candidate for the treatment of Alzheimer’s disease

Alzheimer’s disease(AD)is an age-related neurodegenerative disorder,characterized clinically by insidious onset of memory and cognition impairment,emergence of psychiatric symptoms and behavioral disorder,and impairment of activities of daily living(ADL).Traditional Chinese medicine(TCM)is practiced in the Chinese health care system for more than 2,000 years.In recent years,scientists have isolated many novel compounds from herbs,some of which improve dementia with fewer side effects than conventional drugs and are regarded as potential anti-AD drugs.In this review,we summarize the latest research progress on TCM showing their possible role of treatment of AD and other demented diseases and possible pharmacological actions.

Chinese Medicine for Alzheimer's Disease:A Meta-Analysis of Randomized Controlled Trials

Objective： To evaluate the efficacy of oral Chinese medicine （CM） in comparison with donepezil, a cholinesterase inhibitor （ChEI）, for the treatment of Alzheimer＇s disease （AD）. Methods： Randomized controlled trials （RCTs） have been searched, and the effect of CM compared with donepezil in AD has been investigated. An electronic search of MEDLINE, Excerpta Medica Database （EMBASE）, Cochrane Library, Chinese Biological Medicine Database （CBMdisc）, and China National Knowledge Infrastructure （CNKI） to identify articles in English and Chinese from the inception of the database until October 18, 2015. A modified Jadad score （7-points） to judge the methodological quality of studies, comprehensive meta-analysis was performed with Cochrane Collaboration Revman 5.3. Dichotomous data were analyzed by relative risk （RR） with a 95% confidence interval （CI）, while continuous variables were analyzed by using mean differences （MD） with 95% CI for effect size. Results： Six studies involving 596 AD patients through Jadad assessment with low bias were included in the meta-analysis. No significant difference was observed in cognitive improvement and daily abilities of patients using the Mini Mental State Examination （MMSE） （MD： 0.69, 95% CI： -0.17 to 1.56） and Activities of Daily Living （ADL） scale （MD： 0.94, 95% CI： -1.54 to 3.43）. There were no significant differences in status of illness or MD for mUd-moderate AD patients at 24 weeks （MD： 0.62, 95% CI： -2.99 to 4.23） and 48 weeks （MD： -0.73, 95% CI： -5.02 to 3.56）. Severe AD patients were also assessed at 24 weeks （MD： 3.13, 95% CI： -6.92 to 13.18） and 48 weeks （MD： 4.23, 95% CI： -6.38 to 14.84）. Furthermore, compared with donepezil, Xin （Heart）-regulating CM and Shen （Kidney）-tonifying groups were observed （MD： -1.50, 95% CI： -3.08 to 0.08; MD： -1.92, 95% CI： -3.50 to -0.33; respectively）. CM had fewer side effects in AD patients. Conclusion： Compared with donepezil, oral CM showed no significant difference in effectiveness in AD patients, and more evidence is needed to verify the findings.

Roles of Gut Microbiota in Pathogenesis of Alzheimer's Disease and Therapeutic Effects of Chinese Medicine

Alzheimer’s disease(AD)is the most common neurodegenerative disease characterized by progressive cognitive impairment.The pathogenesis of AD is complex,and its susceptibility and development process are affected by age,genetic and epigenetic factors.Recent studies confirmed that gut microbiota(GM)might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflammatory and immune processes.CM formula,herbs,and monomer enjoy unique advantages to treat and prevent AD.Hence,the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD.Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed.The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.

Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve.However,it remains unclear regarding the effects of Lycium barbarum polysaccharides,the main component of Lycium barbarum,on in vivo proliferation of adult ciliary body cells.In this study,adult rats were intragastrically administered low-and high-dose Lycium barbarum polysaccharides（1 and 10 mg/kg）for 35 days and those intragastrically administered phosphate buffered saline served as controls.The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups,in particular low-dose Lycium barbarum polysaccharides group,was significantly greater than that in the phosphate buffered saline group.Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein.These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype.

Compound Formula Rehmannia alleviates levodopainduced dyskinesia in Parkinson's disease

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.

Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation

The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.

Effects of Zhichan powder on signal transduction and apoptosis-associated gene expression in the substantia nigra of Parkinson's disease rats

Previous studies have shown that Zhichan powder elevated immunity and suppressed oxidation in mice. Rat models of Parkinson＇s disease were induced by stereotaxically injecting 6-hydroxydopamine into the substantia nigra. The rat models were intragastrically treated with Zhichan powder, which is composed of milkvetch root, ginseng, bunge swallowwort root, himalayan teasel root. Magnolia officinalis, Ligustrum lucidum Ait. and szechwan Iovage rhizome. Immunohistochemistry and reverse transcription-PCR results demonstrated that mRNA and protein expression of tumor necrosis factor receptor 1, Fas, caspase-8, cvtochrome C, Bax, casDase-3, and p53 significantly increased, but Bcl-2 expression significantly decreased in the substantia nigra of rats with Parkinson＇s disease. Following Zhichan powder administration, mRNA and protein expression of tumor necrosis factor receptor 1, Fas, caspase-8, cytochrome C, Bax, caspase-3, and p53 diminished, but Bcl-2 expression increased in the rat substantia nigra. These results indicate that Zhichan powder regulates signal transduction protein expression, inhibits apoptosis, and exerts therapeutic effects on Parkinson＇s disease.

The effect of conduction exercise and selfacupressure in treatment of Parkinson’s disease:Protocol for a pilot study

Objective:Parkinson’s disease(PD)is the second most common neurodegenerative disease in the world.In 2004,approximately 13,000 individuals in Hong Kong,China,had PD.PD greatly affects quality of life and conventional medication can produce severe side effects.The traditional Chinese medicine(TCM)practices of conduction exercise(CE)and selfacupressure(SA)may relieve PD symptoms.This paper presents a protocol for a randomized controlled trial to determine the effectiveness of CE and SA in treating PD.Methods:Patients with primary PD were recruited.Eligible patients were randomly assigned to either a treatment or control group.The assessor and data analysts were blind.The treatment phase duration was 8 weeks,with 8 weekly sessions of CE and SA practice.Baseline,midpoint,and final assessments were carried out during the treatment phase.The primary outcome is scores on the 39-item Parkinson’s Disease Questionnaire(PDQ-39),and the secondary outcome is scores on a custom-designed questionnaire based on TCM“Deficiency of Spleen Qi”scores and scores on a non-motor PD symptoms scale.Discussion:This trial is the first rigorous study of the effectiveness of CE and SA in relieving PD symptoms.The aim is to examine the effectiveness of CE and SA in treating a disease that is difficult to treat conventionally.The data obtained will form the foundation for future related studies.Trial registration:Chinese Clinical Trial Registry(ChiCTR-IPR-17011987,Date of registration:14 July,2017).