Screening for phosphodiesterase inhibitory activity of Thai medicinal plants

INTRODUCTION: Phosphodiesterases (PDEs) are a group of enzymes that have powerful effects on cellular signaling because they regulate the second messenger, cAMP or cGMP. PDE inhibitors have been used for treatment of many indications such as cardiovascular diseases, chronic obstructive pulmonary diseases, erectile dysfunction and pulmonary hypertension. THE AIM OF THE STUDY: The aim of the study was to search for sources of PDE inhibitors from Thai biodiversity. MATERIALS AND METHODS: Some Thai medicinal plants used as aphrodisiac and neurotonic agents together with plants from Leguminosae collected from the North of Thailand were screened for PDE inhibitory activity using a radioassay. RESULTS: Seven from nineteen aphrodisiac and neurotonic plants as well as three from twelve Leguminosae plants showed potent PDEs inhibitory activity. The concentrations that could inhibit 50% PDE activity (IC(50)) of the active extracts were determined in comparison to the standard inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Betula alnoides, Hiptage benghalensis, Leea indica and Senna surrattensis showed IC(50) values in the range of microgram per milliliter while IBMX standard showed an IC(50) value of 0.68+/-0.13 microg/ml. CONCLUSION: Thai biodiversity was the great sources of PDE inhibitors.     

Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins

Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.     

Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles

A new nanoparticulate delivery system for amphotericin B (AmB) has been developed by means of the polyelectrolyte complexation technique. Two opposite charged polymers were used to form nanoparticles through electrostatic interaction, chitosan (CH) as a positively charged polymer and dextran sulfate (DS) as a polymer with a negative charge, together with zinc sulfate as a crosslinking and hardening agent. The AmB nanoparticles obtained possessed a mean particle size of 600-800 nm with a polydispersity index of 0.2, indicating a narrow size distribution. The measured zeta potential of the nanoparticle surface was approximately -32 mV indicating a strong negative charge at the particle's surface. Scanning electron microscopy revealed spherical particles with a smooth surface. Drug association efficacy of up to 65% was achieved. Dissolution studies demonstrated a fast release behavior suggesting that AmB exhibits only moderate interaction with the weakly crosslinked polymers of the nanoparticles. Although, electronic absorbance spectra showed that the aggregation state of AmB was modified within the nanoparticles, a reduction of nephrotoxicity was observed in an in vivo renal toxicity study.     

High intrinsic oxidative stress may underlie selective vulnerability of the hippocampal CA1 region

Oxidative stress (OS) causes extensive cell death in the CA1 but not the CA3 region of the hippocampus. We found that the CA1 region of hippocampus explants, cultured under normal conditions, had significantly higher superoxide levels and expressed both anti-oxidant genes and genes related to the generation of reactive oxygen species at significantly higher levels than the CA3. These observations were indicative of high intrinsic OS in CA1.     

Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture

Aim of the study

Bacopa monnieri (Brahmi) is extensively used in traditional Indian medicine as a nerve tonic and thought to improve memory. To examine the neuroprotective effects of Brahmi extract, we tested its protection against the beta-amyloid protein (25–35) and glutamate-induced neurotoxicity in primary cortical cultured neurons.

Materials and Methods

Neuroprotective effects were determined by measuring neuronal cell viability following beta-amyloid and glutamate treatment with and without Brahmi extract. Mechanisms of neuroprotection were evaluated by monitoring cellular oxidative stress and acetylcholinesterase activity.

Results

Our result demonstrated that Brahmi extract protected neurons from beta-amyloid-induced cell death, but not glutamate-induced excitotoxicity. This neuroprotection was possibly due to its ability to suppress cellular acetylcholinesterase activity but not the inhibition of glutamate-mediated toxicity. In addition, culture medium containing Brahmi extract appeared to promote cell survival compared to neuronal cells growing in regular culture medium. Further study showed that Brahmi-treated neurons expressed lower level of reactive oxygen species suggesting that Brahmi restrained intracellular oxidative stress which in turn prolonged the lifespan of the culture neurons. Brahmi extract also exhibited both reducing and lipid peroxidation inhibitory activities.

Conclusions

From this study, the mode of action of neuroprotective effects of Brahmi appeared to be the results of its antioxidant to suppress neuronal oxidative stress and the acetylcholinesterase inhibitory activities. Therefore, treating patients with Brahmi extract may be an alternative direction for ameliorating neurodegenerative disorders associated with the overwhelming oxidative stress as well as Alzheimer's disease.     

Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract

Ethnopharmacological relevance

Bacopa monnieri has a long history in Ayurvedic medicine for neurological and behavioral defects. To assess its efficacy in improving cognitive function.

Materials and methods

MEDLINE, EMBASE, CINAHL, AMED, Cochrane Central of clinical trial, WHO registry, Thai Medical Index, Index Medicus Siriraj library and www.clinicaltrial.gov were searched from the inception date of each database to June 2013 using scientific and common synonyms of Bacopa monnieri, cognitive performance or memory. The reference lists of retrieved articles were also reviewed. Randomized, placebo controlled human intervention trials on chronic ≥12 weeks dosing of standardized extracts of Bacopa monnieri without any co-medication were included in this study. The methodological quality of studies was assessed using Cochrane's risk of bias assessment and Jadad's quality scales. The weighted mean difference and 95% confidence interval (95% CI) were performed using the random-effects model of the Dersimonian–Laird method.

Results

Nine studies met the inclusion criteria using 518 subjects. Overall quality of all included trials was low risk of bias and quality of reported information was high. Meta-analysis of 437 eligible subjects showed improved cognition by shortened Trail B test (−17.9 ms; 95% CI −24.6 to −11.2; p<0.001) and decreased choice reaction time (10.6 ms; 95% CI −12.1 to −9.2; p<0.001).

Conclusion

This meta-analysis suggests that Bacopa monnieri has the potential to improve cognition, particularly speed of attention but only a large well designed ‘head-to-head’ trial against an existing medication will provide definitive data on its efficacy on healthy or dementia patients using a standardized preparation.