Humans ; Parkinson Disease/drug therapy* ; Prevalence ; Southeast Asian People ; Psychotic Disorders/drug therapy* ; Antipsychotic Agents

Corpus Striatum ; Dopaminergic Neurons ; Humans ; Mesencephalon ; Parkinson Disease/drug therapy* ; Pars Compacta ; Substantia Nigra

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1β, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.
Animals ; Gastrointestinal Microbiome ; NF-kappa B/metabolism* ; Nardostachys/metabolism* ; Parkinson Disease/drug therapy* ; Rats ; Rats, Sprague-Dawley

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease. It results from the death of dopaminergic neurons. The pathophysiological mechanisms in idiopathic PD include the production of α-synuclein and mitochondrial respiratory function-affecting complex I, caused by reactive oxygen species. Therefore, the use of natural antioxidants in PD may provide an alternative therapy that prevents oxidative stress and reduces disease progression. In this review, the effects of hydroxytyrosol, Ginkgo biloba, Withania somnifera, curcumin, green tea, and Hypericum perforatum in PD animal and cell line models are compared and discussed. The reviewed antioxidants show evidence of protecting neural cells from oxidative stress in animal and cell models of PD. However, the clinical efficacy of these phytochemicals needs to be optimised and further investigated.
Animals ; Antioxidants/pharmacology* ; Cell Line ; Disease Models, Animal ; Models, Animal ; Neurodegenerative Diseases ; Oxidative Stress ; Parkinson Disease/drug therapy*

Heart Diseases/epidemiology* ; Humans ; Parkinson Disease/drug therapy* ; Propolis

Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

OBJECTIVEThe main objective of this study was to preliminarily determine the optimum formulation of a Chinese herbal formula that may have neuroprotective effects against rotenone-induced Parkinson's disease (PD).

METHODSSeven recipes were made from Dihuang (DH, Rehmannia glutinosa Libosch), Roucongrong (RCR, Cistanche deserticola Y.C.Ma), Niuxi (NX, Achyranthes bidentata Bl.) and Shanzhuyu (SZY, Cornus officinalis Sieb. et Zucc) in different proportions, according to the principles of uniform design (4 factors 7 levels). Tyrosine hydroxylase (TH)-positive neurons in substantia nigra pars compacta (SNpc) were detected by immunohistochemistry and rotenone-exposure days necessary to induce PD symptoms were recorded. To probe one likely mechanism of the formulas, echinacoside (ECH) concentrations of all seven recipes were determined by high-performance liquid chromatography and related to number of TH-positive neurons.

RESULTSThe data showed that recipe 4 (DH:RCR:SZY:NX = 1:1:1:1) and recipe 7 (DH:RCR:SZY:NX = 7:5:3:1) partially reversed rotenone-induced death of TH-positive neurons in the SNpc and significantly increased rotenone-exposed days compared with model group. Pharmacologically, there was not a strong correlation between ECH concentration and TH-positive neurons.

CONCLUSIONThe investigated formulations of Chinese herbs had neuroprotective effects against PD models, and the neuroprotective effects were weakly related to the proportion of key herbs. However the neuroprotective effects of the formula may not result from a single active constituent.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Male ; Neuroprotective Agents ; administration & dosage ; chemistry ; Parkinson Disease ; drug therapy ; etiology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Rotenone ; adverse effects

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents ; toxicity ; Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Electroacupuncture ; methods ; Functional Laterality ; drug effects ; Male ; Medial Forebrain Bundle ; injuries ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Oxidopamine ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism ; Up-Regulation ; drug effects ; physiology ; Vesicular Glutamate Transport Protein 1 ; metabolism

OBJECTIVE: To investigate the effect of rapamycin on Parkinson's disease (PD) and its underlying mechanism in mice. METHODS: Sixty SPF adult male C57BL/6 mice were randomly divided into control group, model group and treatment group. 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) was used to induce Parkinson's disease in model group and treatment group. All mice were trained to cross the runway and were subjected to computer-assisted CatWalk. The numbers of tyrosine hydroxylase positive (TH) neurons in the substantia nigra (SN) were assessed by unbiased stereology using the optical fractionator method; protein expression was detected by Western blot analysis; and glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by spectrophotometry. RESULTS: In the model group, a decrease in stride rate and an increase in variation of stance and swing were noted by CatWalk system (<0.05 or <0.01); the numbers of TH neurons decreased (<0.01); expression of p-Akt, p-S6K, p-S6 and p-ULK increased (all <0.01); LC3-Ⅱ/Ⅰ ratio decreased (<0.01); MDA level was elevated while the levels of SOD and GSH-PX were reduced (all <0.01). Compared with the model group, after treated with rapamycin, the abnormal behavior including the stride length, variation of stance and swing and step patterns induced by MPTP were all improved (<0.05 or <0.01); the numbers of TH neurons increased (<0.05); the expression of p-Akt, p-S6K, p-S6 and p-ULK was suppressed (all <0.01); the LC3-Ⅱ/Ⅰ ratio was upregulated (<0.05); MDA level decreased while the levels of GSH-Px and SOD increased (all <0.01). CONCLUSIONS Rapamycin inhibits the activation of mTOR pathway, which contributes to protect against the loss of dopaminergic neurons and provide behavioral improvements in mice with Parkinson's disease. These results are partially related to the ability of rapamycin in inducing autophagy and reducing oxidative stress.
Animals ; Behavior, Animal ; drug effects ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Oxidative Stress ; drug effects ; Parkinson Disease ; drug therapy ; Random Allocation ; Sirolimus ; pharmacology ; therapeutic use ; Substantia Nigra ; drug effects

OBJECTIVETo evaluate the efficacy of Chinese medicine (CM) adjunct to conventional medications for idiopathic Parkinson's disease (PD).

METHODSElectronic English and Chinese databases including PubMed, Cochrane Library, Web of Science, Chinese Medical Current Contents, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Med Database, and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy. The extracted data was analyzed by the Review Manager 5.0.

RESULTSTwelve trials involving 869 participants were included in the meta-analysis. Unified PD Rating Scale (UPDRS) I, II, III, IV scores and UPDRS V-IV total scores were used to be the primary outcomes, Parkinson Disease Question-39 (PDQ-39) and Scores of Chinese Medical Symptoms were the secondary outcomes. CM adjunct therapy had greater improvement in UPDRS I [2 trials; standardized mean difference (SMD)-0.40, 95% confidence interval (CI)-0.71 to-0.09; Z=2.49 (P=0.01)], II [5 trials; SMD-0.47, 95% CI-0.69 to-0.25; Z=4.20 (P<0.01)], III [5 trials; SMD-0.35, 95% CI-0.57 to-0.13; Z=3.16 (P=0.002)], IV scores [3 trials; SMD-0.32, 95% CI-0.60 to-0.03; Z=2.17 (P=0.03)], UPDRS I-IV total scores [7 trials; SMD-0.36, 95%CI-0.53 to-0.20; Z=4.24 (P<0.05)]. PDQ-39 and Chinese medical symptoms compared to the conventional medication only.

CONCLUSIONCM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.

Humans ; Medicine, Chinese Traditional ; adverse effects ; Parkinson Disease ; drug therapy ; Publication Bias ; Randomized Controlled Trials as Topic ; Surveys and Questionnaires ; Treatment Outcome