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Delivering drugs to the brain has always remained a challenge for the research community and physicians. The blood–brain barrier (BBB) acts as a major hurdle for delivering drugs to specific parts of the brain and the central nervous system. It is physiologically comprised of complex network of capillaries to protect the brain from any invasive agents or foreign particles. Therefore, there is an absolute need for understanding of the BBB for successful therapeutic interventions. Recent research indicates the strong emergence of zebrafish as a model for assessing the permeability of the BBB, which is highly conserved in its structure and function between the zebrafish and mammals. The zebrafish model system offers a plethora of advantages including easy maintenance, high fecundity and transparency of embryos and larvae. Therefore, it has the potential to be developed as a model for analysing and elucidating the permeability of BBB to novel permeation technologies with neurospecificity. Nanotechnology has now become a focus area within the industrial and research community for delivering drugs to the brain. Nanoparticles are being developed with increased efficiency and accuracy for overcoming the BBB and delivering neurospecific drugs to the brain. The zebrafish stands as an excellent model system to assess nanoparticle biocompatibility and toxicity. Hence, the zebrafish model is indispensable for the discovery or development of novel technologies for neurospecific drug delivery and potential therapies for brain diseases. [ABSTRACT FROM AUTHOR]

Objective: Phenotype based small molecule discovery is a category of chemical genetic study. The aim of this study was to observe the phytochemical based genetic effects of Sargassum wightii during organogenesis in embryonic zebrafish. Materials and Methods: The phytomolecules from S. wightii were extracted using organic solvents and treated with the 24 hold developing zebrafish embryos. The active extract was partially purified by column chromatography, C18 Sep-Pak column and reversed-phase high-performance liquid chromatography. Results: Initially, cardiac bulging was found in 2 dpf to 3 dpf (days post fertilization), then bradycardia and tubular heart were observed in the next 8 h, which also showed the reduction in the heart beat rates. The phenotypic mutation effects of bre, has, dou yan, heg and you were observed in the 3 dpf and 4 dpf of the extract treated zebrafish embryos. Conclusions: This study demonstrated that the phytomolecules from S. wightii exhibited potential molecular switches on the developmental process, which might have significant role in understanding the development based chemical genetic studies in zebrafish. [ABSTRACT FROM AUTHOR]

Background: Zebrafish is an important model organism for human neurobehavioural studies and compound screening for neurodegenerative disorders like Alzheimer's disease and dementia. Purpose: We wanted to analyse the rapid neurobehavioural effects based on acetylcholinesterase inhibitors from Tephrosia purpurea in zebrafish. Methods: Tephrosia purpurea (a herbal neuroactive molecule) extract was analyzed for its rapid neurobehavioural effects and the corresponding psychotic twitches were quantified. The inhibitory activity of acetylcholinesterase was analysed in Zebrafish. The activity of the molecule was confirmed after column chromatography and RP-HPLC purifications. The toxicity of the molecule was also studied in developing zebrafish embryos. Results: The psychotic body twitches were calculated as crude 484.67 ± 18.01 at 10 μg/ mL, column purified 616 ± 9.64 at 8 μg/mL, Sep-Pak C18 712.67 ± 19.5 at 6 μg/mL, and HPLC elution showed 815 ± 14.93. The minimum inhibitory concentration of acetylcholinesterase in crude and column purified was 100 ng/mL and 5 ng/mL. The IC50 value of acetylcholinesterase inhibitor was calculated as 626ng/mL for crude (P<0.000l), 28.92 ng/mL for Sep-Pak column elution and 64 ng/mL for Donepezil. The HPLC fifth elation showed inhibition percentage as 96.97 ± 0.12. The organogenesis effects were seen in the drug concentration of 10 ag/mL. Pericardial bulging, trunk and tail flexure with heart edema and head edema were observed in the embryos at higher dose of 30-40 μg The LC50 value was 34.87μg/mL. The studies showed that the inhibitory concentration of acetylcholinesterasn is comparatively higher than Donepezil. Conclusions. Rapid behaviour based screening us an unexpesive assay to identify neuroactive small molecules. This herbal can be further used for the development of drugs for Alzheimers disease. [ABSTRACT FROM AUTHOR]

• Hesperidin alleviates 6−OHDA induced neurotoxicity in SHSY-5Y cells. • Hesperidin rescues MMP and mitigates ROS accumulation. • 6−OHDA causes downregulation of lrrk2, polg, gsk3β, and casp9. • Treatment with hesperidin demoted kinases expression, improved locomotor behavior. The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3β have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6−OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6−OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3β along with casp3 , casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6−OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6−OHDA model of PD. [ABSTRACT FROM AUTHOR]