Identification of Polyphenolics from Loranthus globosus as Potential Inhibitors of Cholinesterase and Oxidative Stress for Alzheimer's Disease Treatment.

Mistletoes are considered to be the potential medicinal herbs due to their rich traditional uses. Loranthus globosus is a Bangladeshi mango mistletoe that has been reported as folk medicine for various ailments and diseases. In an attempt to explore its effectiveness in Alzheimer's disease (AD), we investigated the antioxidant and acetylcholinesterase inhibitory activity of L. globosus. We report that the crude methanol extract (CME) of the plant contains a good amount of polyphenolics and possesses antioxidant and cholinesterase inhibitory activity. Fractionation of CME with solvents of varying polarity revealed the highest activity and polyphenolic content in the ethylacetate fraction (EAF). Correlation analysis revealed a significant (P < 0.05) association of polyphenolics with the antioxidant and cholinesterase inhibitory properties. Using column chromatography with diaion resin, the polyphenolics (EAF-PP) were isolated from the EAF that displayed the potent antioxidant and cholinesterase inhibitory activities. Kinetic analysis showed that EAF-PP exhibited a competitive type of inhibition. A total of thirty-six compounds including catechin and its different derivatives were identified in the EAF-PP by LC/MS analysis. Bioactivity-guided separation approach afforded the isolation of the two major active compounds catechin and catechin dimer from the EAF-PP. Hence, EAF-PP represents a potential source of antioxidants and cholinesterase inhibitors, which can be used in the management of AD.

Evaluation of cholinesterase inhibitory and antioxidant activity of Wedelia chinensis and isolation of apigenin as an active compound.

BACKGROUND: Wedelia chinensis has been reported as a folk medicine for the treatment of different diseases including neurodegenerative disease. Although the plant has been studied well for diverse biological activities, the effect of this plant in neurological disorder is largely unknown. The present study was undertaken to evaluate the cholinesterase inhibitory and antioxidant potential of W. chinensis. METHODS: The extract and fractions of the plant were evaluated for acetylcholinesterase and butyrylcholinesterase inhibitory activity by modified Ellman method. The antioxidant activity was assessed in several in vitro models/assays such as reducing power, total antioxidant capacity, total phenolic and flavonoid content, scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical and hydroxyl radical, and inhibition of brain lipid peroxidation. Chromatographic and spectroscopic methods were used to isolate and identify the active compound from the extract. RESULTS: Among the fractions, aqueous fraction (AQF) and ethylacetate fraction (EAF) exhibited high inhibition against acetylcholinesterase (IC50: 40.02 ± 0.16 µg/ml and 57.76 ± 0.37 µg/ml) and butyrylcholinesterase (IC50: 31.79 ± 0.18 µg/ml and 48.41 ± 0.05 µg/ml). Similarly, the EAF and AQF had high content of phenolics and flavonoids and possess strong antioxidant activity in several antioxidant assays including DPPH and hydroxyl radical scavenging, reducing power and total antioxidant activity. They effectively inhibited the peroxidation of brain lipid in vitro with IC50 values of 45.20 ± 0.10 µg/ml and 25.53 ± 0.04 µg/ml, respectively. A significant correlation was observed between total flavonoids and antioxidant and cholinesterase inhibitory activity. Activity guided chromatographic separation led to the isolation of a major active compound from the EAF and its structure was elucidated as apigenin by spectral analysis. CONCLUSIONS: The potential ability of W. chinensis to inhibit the cholinesterase activity and peroxidation of lipids suggest that the plant might be useful for the management of AD.

Acetylcholinesterase Inhibitory and Antioxidant Activity of the Compounds Isolated from Vanda roxburghii.

Vanda roxburghii has been used in traditional medicine to treat nervous system disorders including Alzheimer's disease (AD). We reported earlier a high acetylcholinesterase inhibitory and antioxidant activity in the chloroform fraction of this plant. Therefore, this study was designed to explore the compounds with acetylcholinesterase inhibitory and antioxidant activities from the chloroform fraction of Vanda roxburghii. Phytochemical investigation led to the isolation for the first time of a fatty acid ester: methyl linoleate (1), and three phenolics: syringaldehyde (2), vanillin (3), and dihydroconiferyl dihydro-p-coumarate (4) along with the previously reported compound gigantol (5). Among the isolates, vanillin (3) and dihydroconiferyl dihydro-p-coumarate (4) were found to significantly inhibit the activity of acetylcholinesterase, scavenge the free radicals, exhibit the reducing power and total antioxidant activity, and effectively reduce the peroxidation of lipid. Gigantol (5) and syringaldehyde (2), despite lacking the activity against acetylcholinesterase, exhibited antioxidant activity. Among the compounds, gigantol (5) appeared to be the most potent antioxidant. These findings revealed that V. roxburghii contained compounds with potential acetylcholinesterase inhibitory and antioxidant activity, which support its traditional use in the treatment of AD.

Phytochemical Analysis and Cholinesterase Inhibitory and Antioxidant Activities of Enhydra fluctuans Relevant in the Management of Alzheimer's Disease.

Enhydra fluctuans, a popular vegetable in Bangladesh, is used in folk medicine to treat diseases of the nervous system. The objective of this study was to investigate the phytochemical profile and cholinesterase inhibitory and antioxidant potential of the extracts of E. fluctuans. Among the four tested extracts, the chloroform extract was found to exert the highest inhibition against both the acetylcholinesterase and butyrylcholinesterase enzymes with the IC50 (concentration required for 50% inhibition) values of 83.90 µg/mL and 48.14 µg/mL, respectively. Likewise, the chloroform extract showed the highest radical scavenging activity and reducing power. In DPPH radical scavenging assay, the IC50 value was found to be 113.27 µg/mL, and in reducing power assay, the absorbance was found to be 1.916 at a concentration of 50 µg/mL. Phytochemical analyses revealed that the chloroform extract contained 19.16 mg gallic acid equivalent (GAE)/g extract of phenolics and 41.84 mg catechin equivalent (CE)/g extract of flavonoids, which appeared to be the highest among the extracts. A significant correlation was observed between phenolic content and butyrylcholinesterase inhibition and antioxidant activity, while a moderate correlation was seen between flavonoid content and cholinesterase inhibition and antioxidant activity. These findings suggest that E. fluctuans is a natural source of cholinesterase inhibitors and antioxidants, which could be utilized as functional foods for Alzheimer's disease management.

In vitro acetylcholinesterase inhibitory activity and the antioxidant properties of Aegle marmelos leaf extract: implications for the treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by loss of memory and cognition. The effective therapeutic options for AD are limited and thus there is a demand for new drugs. Aegle marmelos (Linn.) (A. marmelos) leaves have been used in traditional medicine to promote intellect and enhance memory. In this study, we evaluated A. marmelos for its acetylcholinesterase (AChE) inhibitory activity and antioxidant property in vitro in the treatment of AD. METHODS: A crude methanol extract and four fractions (petroleum ether, chloroform, ethyl acetate and aqueous) were prepared from the leaves of A. marmelos. The preparations were assessed for AChE inhibitory activity by the Ellman method, and their antioxidant properties were assessed by several assays: reducing power, scavenging of 1,1-diphenyl-2-picrylhydrazyl free radical and hydroxyl radical, and inhibition of lipid peroxidation. Qualitative and quantitative analyses of endogenous substances in A. marmelos were performed by the standard phytochemical methods. RESULTS: Among the different extracts tested, the ethyl acetate fraction exhibited the highest inhibition of AChE activity. In the same way, ethyl acetate fraction showed the highest reducing activity and radical scavenging ability towards the 1,1-diphenyl-2-picrylhydrazyl (half maximal inhibitory concentration = 3.84 µg/mL) and hydroxyl free radicals (half maximal inhibitory concentration = 5.68 µg/mL). The antiradical activity of the ethyl acetate fraction appeared to be similar to that of the reference standard butylated hydroxytoluene and catechin used in this study. In addition, the ethyl acetate fraction displayed higher inhibition of brain lipid peroxidation. Phytochemical screening of different extractives of A. marmelos showed the presence of phenols and flavonoids, alkaloid, saponin, glycoside, tannin and steroids. Quantitative analysis revealed higher contents of phenolics (58.79-mg gallic acid equivalent/g dried extract) and flavonoids (375.73-mg gallic acid equivalent/g dried extract) in the ethyl acetate fraction. CONCLUSION: The results suggest that the ethyl acetate fraction of A. marmelos is a significant source of polyphenolic compounds with potential AChE inhibitory property and antioxidant activity and, thus, may be useful in the treatment of AD.

Regularization using similarities of signals observed in nearby sensors for feature extraction of brain signals.

In order to solve uncertainty of spatial weights learned with small amount of training samples for feature extraction from brain signals, a regularization using similarity of signals observed in sensors that are located near each other is proposed. Deriving the regularization is begun defining a distance between the sensors. Under the distance, the proposed regularization works so that the spatial weights extracts similar signals in the nearby sensors. The proposed regularization is applied to the well known common spatial pattern (CSP) method that finds spatial weights for EEG based brain machine interface. In the classification experiment using a dataset of EEG signals during motor imagery, the proposed method achieved maximum improvement by 28% in the classification accuracy over the standard CSP in a setting of even when only five samples are used.

Time sparsification of EEG signals in motor-imagery based brain computer interfaces.

We propose a method of sparsifying EEG signals in the time domain for common spatial patterns (CSP) which are often used for feature extraction in brain computer interfaces (BCI). For accurate classification, it is important to analyze the period of time when a BCI user performs a mental task. We address this problem by optimizing the CSP cost with a time sparsification that removes unnecessary samples from the classification. We design a cost function that has CSP spatial weights and time window as optimization parameters. To find these parameters, we use alternating optimization. In an experiment on classification of motor-imagery EEG signals, the proposed method increased classification accuracy by 6% averaged over five subjects.

Optimal design of a bank of spatio-temporal filters for EEG signal classification.

The spatial weights for electrodes called common spatial pattern (CSP) are known to be effective in EEG signal classification for motor imagery based brain computer interfaces (MI-BCI). To achieve accurate classification in CSP, the frequency filter should be properly designed. To this end, several methods for designing the filter have been proposed. However, the existing methods cannot consider plural brain activities described with different frequency bands and different spatial patterns such as activities of mu and beta rhythms. In order to efficiently extract these brain activities, we propose a method to design plural filters and spatial weights which extract desired brain activity. The proposed method designs finite impulse response (FIR) filters and the associated spatial weights by optimization of an objective function which is a natural extension of CSP. Moreover, we show by a classification experiment that the bank of FIR filters which are designed by introducing an orthogonality into the objective function can extract good discriminative features. Moreover, the experiment result suggests that the proposed method can automatically detect and extract brain activities related to motor imagery.

Laughter and humor as complementary and alternative medicines for dementia patients.

BACKGROUND: The number of dementia patients has increased worldwide, with an estimated 13.7 million dementia patients in the Asia Pacific region alone. This number is expected to increase to 64.6 million by the year 2050. DISCUSSION: As a result of advances in research, there several pharmacological therapies available for the treatment of dementia patients. However, current treatments do not suppress the disease process and cannot prevent dementia, and it will be some time before these goals are realized. In the meantime, complementary and alternative medicine (CAM) is an important aspect in the treatment of dementia patients to improve their quality of life throughout the long course of the disease. Considering the individuality of dementia patients, applicability of laughter and humor therapy is discussed. Even though there are many things that need to be elucidated regarding the mechanisms underlying the beneficial effects of laughter and humor, both may be good CAM for dementia patients if they are applied carefully and properly. SUMMARY: In this debate article, the physiological basis and actual application of laughter and humor in the treatment of dementia patients are presented for discussion on the applicability to dementia patients.

Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.

This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia.

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.