GINGER LOADED CHITOSAN NANOPARTICLES FOR THE MANAGEMENT OF 3–NITROPROPIONIC ACID-INDUCED HUNTINGTON’S DISEASE-LIKE SYMPTOMS IN MALE WISTAR RATS

Objective: The purpose of this research work is to enhance bioavailability and brain delivery of ginger through the development of ginger-loaded chitosan nanoparticles and evaluation of its neuroprotective potential against 3-Nitropropionic acid (3-NP) induced Huntington’s Disease model rats. Methods: Ginger-loaded chitosan nanoparticles were developed as five different formulations (F1-F5) by the ionic gelation method. Based on their release, formulations F1 and F3 were chosen for physicochemical characterization. The neuroprotective activity of formulations F1 and F3 were evaluated by behavioural (Neurological scoring, Hanging wire test, Elevated plus maze test), biochemical (estimation of lipid peroxidation, glutathione, protein, superoxide dismutase, catalase) and neurochemical (estimation of acetylcholine esterase inhibition) tests in comparison with ginger extract in Huntington’s Disease (HD) model rats. Results: Formulations F1 and F3 showed almost similar and significant controlled release. Formulation F1 showed spherical nanoparticles with optimum size range and negative zeta potential. The behavioural assessment revealed that there was an improvement in gait, movement, grip strength and memory in ginger-loaded chitosan nanoformulations administered to rats than ginger extract administered rats. Biochemical and neurochemical analyses also proved that ginger-loaded chitosan nanoformulations had greatly lowered the oxidative stress parameters such as malondialdehyde and protein carbonyls in comparison with ginger extract (p<0.05). The ginger nanoformulations had highly increased the activity of antioxidant enzymes such as superoxide dismutase, glutathione and catalase by reducing the formation of free radicals than ginger extract (p<0.05). The memory and cognition of ginger nanoformulations administered Wistar rats had highly improved than ginger extract administered Wistar rats (p<0.05 due to inhibition of acetylcholine esterase enzyme). Conclusion: The current study indicated that ginger-loaded chitosan nanoparticles have a superior neuroprotective effect than their extract due to their nano size, which facilitates their entry across the blood-brain barrier and eventually improves the bioavailability of ginger.

In vitro pharmacological attributes and metabolite’s fingerprinting of Conocarpus lancifolius

Search for safe antioxidants and novel nutraceuticals urged to evaluate the antioxidant, anti-acetylcholine esterase and anti-lipoxygenase activity of various leaf extracts of Conocarpus lancifolius. Extraction was optimized from freeze dried plant extracts quenched with liquid nitrogen using water, ethanol, methanol, hexane, ethyl acetate and chloroform. Maximum extract yield, total phenolic contents and total flavonoid contents were obtained in case of ethanolic extraction. The highest 2,2-diphenyl-1-picrylhydrazylradical scavenging in terms of IC50 value of 55.26 µg/mL was observed for ethanolic leaf extract. The acetylcholine esterase and lipoxygenase inhibitory activities (IC50) were also observed for ethanolic extract. These findings for ethanolic extract were statistically significant when compared with other extracts (ρ<0.05). The haemolytic % values indicated that all extracts were associated with very low or negligible toxicity. The epicatechin, isorhamnetin, rutin, scopoleptin, skimmianine, quercetin-3-O-α-rhamnoside, quercetin-3-O-β-glucoside, cornoside, creatinine, choline, pyruvic acid, α-hydroxybutyric acid, phyllanthin and hypophyllanthin were identified as major functional metabolites in ethanolic leaf extract of C. lancifolius by 1H-NMR. The identified metabolites were probably responsible for the pharmacological properties of C. lancifolius. The findings may be utilized as pharmacological leads for drug development and food fortification.

Green Synthesis and Characterization of Zinc Oxide Nanoparticles (ZnO NPs) from Camellia sinensis Leaf Extract and Its Potential of Antibacterial Activity and Acetyl Cholinesterase Inhibitory Activities

Nanoparticles are widely used in the biotechnology and biomedicalfield. Green synthetic methods of nanoparticles are a simple and environmentallybenign process that declines the demerits of conventional chemical andphysical methods. The synthesis of semiconductor and metal nanoparticles is a risingdo research part, due to the possible applications in the progress of new technologies.The present research information the synthesis and characterization of zinc oxide nanoparticles (ZnO NPs) using C. Sinensis leaf extract. The findings of these studies show the green synthesized ZnO NPs are effective, safe, and eco-friendly as they arestable and have abundant flower shapes with maximum particles in size ranging from 100 nm indiameter. The synthesized ZnO NPs have been tested against the pathogenic microorganismsand showed an excellent zone of inhibition. DPPH radical scavenging activity of synthesized ZnO NPs expressed DPPH free radicals as a percentage of inhibition andIC50value of 70.37%. Acetylcholine esterase (AChE) inhibitory activity possesses the maximum amount of the synthesized ZnO NPs. Since the results ofthe current work, it was concluded that the synthesized ZnO NPs exhibited significant antibacterial and acetylcholine esterase inhibitory activities. Hence it can beused as a drug with multifunction in treating Alzheimer’s disease (AD).

Acetylcholine esterase inhibitory activity of green synthesized nanosilver by naphthopyrones isolated from marine-derived Aspergillus niger

Aspergillus niger metabolites exhibited a wide range of biological properties including antioxidant and neuro-protective effects and some physical properties as green synthesis of silver nanoparticles AgNP. The present study presents a novel evidence for the various biological activities of green synthesized AgNPs. For the first time, some isolated naphtho-γ-pyrones from marine-derived Aspergillus niger, flavasperone (1), rubrofusarin B (2), aurasperone A (3), fonsecinone A (4) in addition to one alkaloid aspernigrin A (7) were invistigated for their inhibitory activity of acetylcholine esterase AChE, a hallmark of Alzheimer’s disease (AD). The ability to synthesize AgNPs by compounds 3, 4 and 7 has been also tested for the first time. Green synthesized AgNPs were well-dispersed, and their size was ranging from 8–30 nm in diameter, their morphology was obviously spherical capped with the organic compounds. Further biological evaluation of their AChE inhibitory activity was compared to the parent compounds. AgNps dramatically increased the inhibitory activity of Compounds 4, 3 and 7 by 84, 16 and 13 fold, respectively to be more potent than galanthamine as a positive control with IC50 value of 1.43 compared to 0.089, 0.311 and 1.53 of AgNPs of Compounds 4, 3 and 7, respectively. Also compound 2 showed moderate inhibitory activity. This is could be probably explained by closer fitting to the active sites or the synergistic effect of the stabilized AgNPs by the organic compouds. These results, in addition to other intrinsic chemical and biological properties of naphtho-γ-pyrones, suggest that the latter could be further explored with a view towards other neuroprotective studies for alleviating AD.

Revealing the molecular interplay of curcumin as Culex pipiens Acetylcholine esterase 1 (AChE1) inhibitor

Emergence of vector borne diseases has continued to take toll on millions of lives since its inception. The use of insecticides began as vector control strategy in the early 1900’s but the menace of insects is still prevalent. Additionally, the inadequate use of organophosphates and carbamates which target acetylcholine esterase (AChE), are known to develop resistance amongst vectors of transmission and are toxic to humans. In this study, extensive computational screening was performed using homology modelling, molecular docking, molecular dynamics (MD) simulation and free energy change calculation, which highlighted curcumin as a lead molecule out of ~ 1700 phytochemicals against Culex pipiens AChE. In vivo larvicidal activity was carried out along with in vivo and in vitro AChE inhibition assay to determine the biochemical efficacy of curcumin. Our study reveals that curcumin induces mortality in Cx. pipiens at an early stage of its life cycle by AChE inhibition. This also underlines the use of curcumin as a coming-age natural product insecticide.

Design, synthesis and biological evaluation of substituted pyrazoles endowed with brominated 4-methyl 7-hydroxy coumarin as new scaffolds against Alzheimer’s disease

Background The study aimed to design, synthesize and evaluate various brominated derivatives of 7-hydroxy coumarin as a new scaffold against Alzheimer’s disease by in vivo and in vitro models. A group of three novel pyrazoles endowed with brominated 7-hydroxy 4-methyl coumarin derivatives were designed. Among the designed compounds, a single entity (D1) was selected based on the docking score, which could be considered mainly for the treatment of Alzheimer’s disease. Three novel pyrazoles endowed with brominated 7-hydroxy 4-methyl coumarin derivatives were designed and docking studies of these compounds were carried out using Argus lab4.0.1 version. According to the docking score, a single entity of compound (D1) was selected for further study. The structure of the compound (D1) was explored by spectral analysis. The anti-Alzheimer’s activity was evaluated by in vivo and in vitro methods. All results were compared statistically by one-way ANOVA using GraphPad Prism. Results Molecular docking studies revealed that the compound D1 was able to bind simultaneously to the amino acid and in the active sites of the acetylcholine esterase enzyme. In acetylcholine esterase inhibition assay, the compound shows a significant increase in acetylcholine esterase level. The MAO inhibitory activities were in the nanomole range (human MAO-A IC50 = 3.9, human MAO-B IC 50 = 4.4). DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay showed that the compound shows a promising antioxidant property. In the evaluation of learning and memory of compound D1 using elevated plus maze, the compound D1-pretreated group showed a significant increase in memory and learning when compared with donepezil. Conclusions Among the designed series of pyrazole endowed with brominated 7-hydroxyl 4-methyl coumarin derivatives, compound D1 showed good antioxidant property and acetylcholine esterase and MAO inhibitory activity; based on this property, the synthesized compound D1 can be considered a new scaffold on Alzheimer’s disease.

THE EFFECT OF DURATION OF ACETYLCHOLINE-ESTERASE INHIBITOR ON MMSE, CDT AND BARTHEL INDEX SCORING ON PATIENTS WITH VASCULAR DEMENSIA

Background: Vascular dementia is a cognitive decline with functional deterioration caused by cerebrovascular disease. It is the second leading cause of dementia. A number of screening questionnaires and models have been developed to help in assessing cognitive function and activity daily living (ADL) in patients with dementia. Mini Mental State Examination (MMSE), Clock Drawing Test (CDT) and Barthel Index are instruments to evaluate cognitive function and ADL of vascular dementia patients. Objective: To determine the role of achetylcholine-esterase inhibitor therapy on cognitive function and ADL in patients with vascular dementia in Saiful Anwar General Hospital. Methods: This study is an analytical study assessing the improvement of cognitive function and ADL of patients with vascular dementia after administration of acethylcholine-esterase inhibitor by assessing the MMSE, CDT and Barthel Index scoring in 1, 3, 6 and 12 month period consecutively. Results: From 15 study subjects, individuals who have been given treatment for 12 months consecutively have the highest increase in MMSE and CDT whilst for Barthel Index has shown highest improvement in one month period. Conclusion: The administration of acetylcholine-esterase inhibitor drugs has the potential to improve and maintain cognitive function and improve ADL. The limited number of study subjects and the many confounding factors that we did not evaluate were the drawbacks of this study. The results of this study cannot be generalized to all patients with vascular dementia and only apply to 15 patients who were the subjects of this study.