ABSTRACT
Alzheimer's disease (AD) is a progressive disease and the predominant cause of dementia. Common symptoms include short-term memory loss, and confusion with time and place. Individuals with AD depend on their caregivers for assistance, and may pose a burden to them. The acetylcholinesterase (AChE) enzyme is a key target in AD and inhibition of this enzyme may be a promising strategy in the drug discovery process. In the present study, an inhibitory assay was carried out against AChE using total alkaloidal plants and herbal extracts commonly available in vegetable markets. Subsequently, molecular docking simulation analyses of the bioactive compounds present in the plants were conducted, as well as a proteinligand interaction analysis. The stability of the docked proteinligand complex was assessed by 20 ns molecular dynamics simulation. The inhibitory assay demonstrated that Uncaria rhynchophylla and Portulaca oleracea were able to inhibit AChE. In addition, molecular docking simulation analyses indicated that catechin present in Uncaria rhynchophylla, and dopamine and norepinephrine present in Portulaca oleracea, had the best docking scores and interaction energy. In conclusion, catechin in Uncaria rhynchophylla, and dopamine and norepinephrine in Portulaca oleracea may be used to treat AD.
Subject(s)
Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Alzheimer Disease/drug therapy , Binding Sites , Catalytic Domain , Enzyme Activation/drug effects , Humans , Models, Molecular , Molecular Conformation , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To study the safety of using Chinese drugs for breaking blood expelling stasis (CDBBES) in hypertension patients with intracerebral hemorrhage within 6 h, and to observe whether they would result in hematoma enlargement. METHODS: A prospective randomized double-blind controlled clinical study was employed. Totally 128 cerebral hemorrhage patients within 6 h were recruited from 8 research centers from October 2013 to March 2015, and finally 76 of them were included. These patients were assigned to 3 groups by simple random sampling, group A, B, and C. Patients in group A (26 cases) took whole CDBBES recipe (containing leeches and equivalent insects). Those in group B (25 cases) took CDBBES recipe (removing leech and gradfly). Those in group C (25 cases) took placebos. Medication lasted for 10 successive days. The hematoma enlargement rate within 24 h, the occurrence of adverse reactions and adverse events were observed. To guarantee the safety of this trial, an interim analysis of first level unblinding was used. RESULTS: The hematoma enlargement rate was 11. 5% (3/26) in group A, 16. 0% (4/25) in group B, and 20. 0% (5/25) in group C. There was no statistical difference in the hematoma enlargement rate among the 3 groups (X² =0. 823, P =0. 682). Adverse reactions and adverse events occurred in 7 cases, 1 patient with acute myocardial infarction, 1 with chest op- pression and palpitation, 2 with diarrhea in group A. No patient had adverse reaction or adverse event in group B. And diarrhea occurred in 3 patients of group C. CONCLUSION: The interim analysis of first level unblinding showed that hematoma enlargement within 6 h was not resulted from using CDBBES.
Subject(s)
Cerebral Hemorrhage , Hematoma , Hypertension , Medicine, Chinese Traditional , Cerebral Hemorrhage/drug therapy , Double-Blind Method , Hematoma/drug therapy , Humans , Hypertension/complications , Prospective StudiesABSTRACT
BACKGROUND AND OBJECTIVES: Carotid artery stenting (CAS) is an important therapeutic strategy for patients with carotid artery stenosis. However, the potential influence of CAS on cognitive function in patients with carotid artery stenosis and cerebral lacunar infarction has not been determined. This study investigated changes in cognitive function associated with CAS and the factors related to these changes. METHODS: This prospective cohort study comprised 579 Chinese patients with cerebral lacunar infarction and carotid artery stenosis for whom CAS was indicated, and a matched control group of 552 healthy individuals. Cognitive function before CAS and at scheduled intervals from 6 months to 3 years was assessed with instruments that included the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. Potential factors that might affect cognitive function were analyzed via logistic regression. RESULTS: The MMSE and MoCA scores of the patients before CAS were significantly lower than that of the control subjects. These scores were significantly higher 6 months after CAS and sustained or increased throughout the 3-year follow-up. Also significantly improved after CAS from baseline were scores for an alternating trail test, cube copying, clock-drawing, attention, and delayed recall in an auditory-verbal learning test. Logistic regression analyses showed that age greater than 65 y, little education, diabetes, and hypertension were independent risk factors for deteriorated MoCA scores 3 years after CAS. CONCLUSION: CAS was associated with significantly improved cognitive function in cerebral lacunar infarction patients with severe stenosis.
Subject(s)
Carotid Arteries/physiopathology , Carotid Stenosis/complications , Cognition Disorders/etiology , Cognition , Stents/adverse effects , Stroke, Lacunar/complications , Case-Control Studies , China , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Prognosis , Prospective Studies , Psychomotor Performance , Time FactorsABSTRACT
OBJECTIVE: This study was designed to investigate the relation between plasma von Willebrand factor (VWF) or endothelin-1 (ET-1) and post-carotid artery stenting (CAS) restenosis. MATERIALS AND METHODS: Plasma levels of VWF and ET-1 were measured in 61 patients (36 males, mean age 64.4 ± 6.8 years) before and after CAS. The mean follow-up time was 13.8 ± 1.7 months (range, 6-63). In-stent restenosis was defined as a >10% narrowing of the vascular lumen with or without ischemic symptoms following CAS. RESULTS: In-stent restenosis was identified in 14 (23%) patients, including 3 with >50% restenosis. In the restenosis group, mean VWF and ET-1 levels at 2 weeks, 1 and 6 months after CAS were higher than the baseline levels (p < 0.05 or p < 0.01). Mean levels of VWF and ET-1 in the restenosis group were higher than in the non-restenosis group within 6 months after CAS (p < 0.05 or p < 0.01). CONCLUSION: Persistent elevation in plasma VWF and ET-1 within the first 6 months of CAS was found in patients with in-stent restenosis.
