Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (K ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.
Introduction: Indoor air quality is an important aspect in defining Sick Building Syndrome (SBS). SBS triggered by
inadequate IAQ may harm occupants. Objective: This study was conducted to establish the relationship between
IAQ and SBS in the higher educational building. Methods: The research method is divided into three main categories; indoor air chemical and contaminant analysis, microbiological contaminant analysis, and questionnaire.
A cross-sectional study was conducted at seven locations in a university in Shah Alam. Results: The results were
compared to the Department of Occupational Safety and Health standard (DOSH). Significant correlation with temperature (p<0.05), relative humidity (p<0.05), and particulate matter (PM10) (p<0.05) were found.This study suggests
that enhancing housekeeping standards and monitoring indoor air quality can enhance the indoor air quality in Malaysian higher education buildings. Conclusion: Based on correlation between IAQ and SBS symptoms, poor IAQ
and SBS symptoms among occupants may impact teaching and learning process in the university. Conclusion: This
study suggests that enhancing housekeeping standards and monitoring indoor air quality can enhance the indoor air
quality in Malaysian higher education buildings.
Background: Orthosiphon aristatus has been usually related to be powerful in curing many illnesses inclusive of post-partum remedy, anti-influence, rheumatism and stopping osteoporosis as a result of menopause. Objectives: Thus, this study was designed to differentiate the toxicity effect of non-irradiated and irradiated Orthosiphon aristatus at different dosage of 3, 6, 9 and 12 kilogray (kGy) on zebrafish embryo. Method: Survival rate, hatching rate, heart beat rate and scoliosis were observed and date were analysed using SPSS 25.00 windows. Result: The lethal dose (LC50) of non-irradiated Orthosiphon aristatus is 381.81 μg/mL compare to irradiated extract at 3 % is (371.27 μg/mL), 6 % (311.03 μg/mL), 9 % (160.72 μg/mL) and 12 % (140.18 μg/mL). Hatchability of zebrafish embryo for Orthosiphon aristatus extract decrease in the higher dosage of irradiated sample compared to non-irradiated sample. No presence of scoliosis was observed in all dosage of irradiated and non-irradiated of Orthosiphon aristatus. The heartbeat of zebrafish embryo treated with irradiated Orthosiphon aristatus specifically 12 % show decrease at 250 μg/mL concentration. Remaining dosage of irradiated and non-irradiated Orthosiphon aristatus show average heartbeat around 120 - 160 bpm. Conclusion: As conclusion, irradiated and non-irradiated of Orthosiphon aristatus is safe to be consumed due to its pharmaceutical effect but it still exhibited mild toxicity effect on zebrafish embryo.
HIGHLIGHTS
Herbal medicine (Orthosiphon aristatus) is widely used for treatment as alternative medicine
This Orthosiphon aristatus easy can be contaminated by bacteria and fungus. Gamma ray is helpful to eliminated the bacteria and fungus
Irradiated Orthosiphon aristatus can be toxic due to the exposure in Gamma ray
Toxicity study using zebra fish show no changes in toxicity of Orthosiphon aristatus
GRAPHICAL ABSTRACT
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