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  1. Agarose-chitosan-C18 film micro-solid phase extraction combined with high performance liquid chromatography for the determination of phenanthrene and pyrene in chrysanthemum tea samples
    Ng NT, Sanagi MM, Wan Ibrahim WN, Wan Ibrahim WA
    Food Chem, 2017 May 01;222:28-34.
    PMID: 28041555 DOI: 10.1016/j.foodchem.2016.11.147
    Agarose-chitosan-immobilized octadecylsilyl-silica (C18) film micro-solid phase extraction (μSPE) was developed and applied for the determination of phenanthrene (PHE) and pyrene (PYR) in chrysanthemum tea samples using high performance liquid chromatography-ultraviolet detection (HPLC-UV). The film of blended agarose and chitosan allows good dispersion of C18, prevents the leaching of C18 during application and enhances the film mechanical stability. Important μSPE parameters were optimized including amount of sorbent loading, extraction time, desorption solvent and desorption time. The matrix match calibration curves showed good linearity (r⩾0.994) over a concentration range of 1-500ppb. Under the optimized conditions, the proposed method showed good limits of detection (0.549-0.673ppb), good analyte recoveries (100.8-105.99%) and good reproducibilities (RSDs⩽13.53%, n=3) with preconcentration factors of 4 and 72 for PHE and PYR, respectively.
  2. Agarose- and alginate-based biopolymers for sample preparation: Excellent green extraction tools for this century
    Sanagi MM, Loh SH, Wan Ibrahim WN, Pourmand N, Salisu A, Wan Ibrahim WA, et al.
    J Sep Sci, 2016 Mar;39(6):1152-9.
    PMID: 27027592 DOI: 10.1002/jssc.201501207
    Recently, there has been considerable interest in the use of miniaturized sample preparation techniques before the chromatographic monitoring of the analytes in unknown complex compositions. The use of biopolymer-based sorbents in solid-phase microextraction techniques has achieved a good reputation. A great variety of polysaccharides can be extracted from marine plants or microorganisms. Seaweeds are the major sources of polysaccharides such as alginate, agar, agarose, as well as carrageenans. Agarose and alginate (green biopolymers) have been manipulated for different microextraction approaches. The present review is focused on the classification of biopolymer and their applications in multidisciplinary research. Besides, efforts have been made to discuss the state-of-the-art of the new microextraction techniques that utilize commercial biopolymer interfaces such as agarose in liquid-phase microextraction and solid-phase microextraction.
  3. Fulltext Biochemical Constituent of Ginkgo biloba (Seed) 80% Methanol Extract Inhibits Cholinesterase Enzymes in Javanese Medaka (Oryzias javanicus) Model
    Hassan I, Wan Ibrahim WN, Yusuf FM, Ahmad SA, Ahmad S
    J Toxicol, 2020;2020:8815313.
    PMID: 33029137 DOI: 10.1155/2020/8815313
    Background: Pathophysiological changes leading to the death of nerve cells present in the brain and spinal cord are referred to as neurodegenerative diseases. Presently, treatment of these diseases is not effective and encounters many challenges due to the cost of drug and side effects. Thus, the search for the alternative agents to replace synthetic drugs is in high demand. Therefore, the aim of this study is to evaluate the anticholinesterase properties of Ginkgo biloba seed.

    Methods: The seed was extracted with 80% methanol. Toxicity studies and evaluation of anticholinesterase activities were carried out in adult Javanese medaka (Oryzias javanicus). Phytochemical study to identify the bioactive lead constituents of the crude extract was also carried out using high performance liquid chromatography (HPLC).

    Results: The result shows activities with high significant differences at P < 0.001 between the treated and nontreated groups. A bioactive compound (vitaxin) was identified with the aid of HPLC method.

    Conclusion: The presence of bioactive compound vitaxin is among the major secondary metabolites that contribute to increasing activities of this plant extract. High anticholinesterase activities and low toxicity effect of this plant show its benefit to be used as natural medicine or supplements.

  4. Neuroprotective and antioxidant effect of Curcuma longa (Rhizome) methanolic extract on SH-SY5Y cells and Javanese medaka
    Hassan IM, Wan Ibrahim WN, Yusuf FM, Ahmad SA, Ahmad S
    Pak J Pharm Sci, 2021 Jan;34(1):47-56.
    PMID: 34248002
    Diseases caused by oxidative stress can be prevented by antioxidant. Current treatments for those neurodegenerative diseases are not effective and cause many side effects. Thus, the search for alternative medicines is in high demand. Therefore, the main purposed of this study is to evaluate the neuroprotective effects of Curcuma longa (rhizome) 80% methanol extract. Antioxidant using dichlorofuoresence diacetate (DCF-DA) assay on SH-SY5Y cells revealed high activities of Curcuma longa (rhizome) extract with IC50 of 105.9±0.8 µg/mL. Sub-acute and chronic toxicity tests of the plant extract on adult Javanese medaka (Oryzias javanicus) showed high toxicity effect with LC50 of 24.15±0.8 mg/L and 13.69±0.7 mg/L respectively. Neuroprotective tests using cholinesterase assay disclose significant differences at P<0.05 between the group that are exposed to arsenic and treated with the crude extract and the group that are exposed to only arsenic. Identification of vitexin and isovitexin justified the high antioxidant potential of this plant leaf and it highest benefit to be used as medicinal supplement.
  5. Fulltext Solid-Phase Extraction of Active Compounds from Natural Products by Molecularly Imprinted Polymers: Synthesis and Extraction Parameters
    Kamaruzaman S, Nasir NM, Mohd Faudzi SM, Yahaya N, Mohamad Hanapi NS, Wan Ibrahim WN
    Polymers (Basel), 2021 Oct 31;13(21).
    PMID: 34771337 DOI: 10.3390/polym13213780
    Molecularly imprinted polymers (MIPs) are synthetic polymers with a predetermined selectivity for a particular analyte or group of structurally related compounds, making them ideal materials for separation processes. Hence, in sample preparation, MIPs are chosen as an excellent material to provide selectivity. Moreover, its use in solid-phase extraction, also referred to as molecular imprinted solid phase extraction (MISPE), is well regarded. In recent years, many papers have been published addressing the utilization of MIPs or MISPE as sorbents in natural product applications, such as synthesis. This review describes the synthesis and characterization of MIPs as a tool in natural product applications.
  6. Magnetic micro-solid-phase extraction based on magnetite-MCM-41 with gas chromatography-mass spectrometry for the determination of antidepressant drugs in biological fluids
    Kamaruzaman S, Sanagi MM, Yahaya N, Wan Ibrahim WA, Endud S, Wan Ibrahim WN
    J Sep Sci, 2017 Nov;40(21):4222-4233.
    PMID: 28837263 DOI: 10.1002/jssc.201700549
    A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 μg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 μL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 μg/L (r2  = 0.996-0.999). Good limits of detection (0.008-0.010 μg/L) were obtained for the analytes with good relative standard deviations of <8.0% (n = 5) for the determination of 0.1, 5.0, and 500.0 μg/L of antidepressant drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples.
  7. Behavioral and cortisol analysis of the anti-stress effect of Polygonum minus (Huds) extracts in chronic unpredictable stress (CUS) zebrafish model
    Abdul Rahim N, Nordin N, Ahmad Rasedi NIS, Mohd Kauli FS, Wan Ibrahim WN, Zakaria F
    Comp Biochem Physiol C Toxicol Pharmacol, 2022 Jun;256:109303.
    PMID: 35202824 DOI: 10.1016/j.cbpc.2022.109303
    The World Health Organization (WHO) recorded approximately 350 million people worldwide have suffered from mental health disorders, such as depression, anxiety, schizophrenia, and addictive behaviors. The search for new drugs from nature has drawn on many biological resources and human practices. In this study, leaves of Polygonum minus standardized extract (Biokesum®), 1 and 100 mg/L were used to evaluate the anti-stress effect in the chronic unpredictable stress (CUS) zebrafish model. Five groups of zebrafish were manipulated in this study, comprising control, chronic unpredictable stress (CUS), CUS + Biokesum® 1 mg/L (4 days, 20 min/day, immersion) CUS + Biokesum® 100 mg/L (4 days, 20 min/day, immersion) and CUS + fluoxetine 0.6 mg/L (4 days, 20 min/day, immersion). Four different behavioral tests were used, i.e. open-field test, social interaction test, light and dark test, and exploratory test. After four consecutive days of treatment, the zebrafish were sacrificed for whole-body cortisol analysis. The exploratory test showed a significant change upon P. minus treatment (one-way ANOVA; p = 0.0011). Cortisol analysis showed a decrease of cortisol level after treatment with the extract and fluoxetine, without significant difference. These results showed that zebrafish is a reliable model to study the anti-stress effect of compounds or herbal extract.
  8. Solid-phase microextraction based on an agarose-chitosan-multiwalled carbon nanotube composite film combined with HPLC-UV for the determination of nonsteroidal anti-inflammatory drugs in aqueous samples
    Wan Ibrahim WN, Sanagi MM, Mohamad Hanapi NS, Kamaruzaman S, Yahaya N, Wan Ibrahim WA
    J Sep Sci, 2018 Jul;41(14):2942-2951.
    PMID: 29877605 DOI: 10.1002/jssc.201800064
    We describe the preparation, characterization, and application of a composite film adsorbent based on blended agarose-chitosan-multiwalled carbon nanotubes for the preconcentration of selected nonsteroidal anti-inflammatory drugs in aqueous samples before determination by high performance liquid chromatography with ultraviolet detection. The composite film showed a high surface area (4.0258 m2 /g) and strong hydrogen bonding between the multiwalled carbon nanotubes and agarose/chitosan matrix, which prevent adsorbent deactivation and ensure long-term stability. Several parameters, such as sample pH, addition of salt, extraction time, desorption solvent, and concentration of multiwalled carbon nanotubes in the composite film were optimized using a one-factor-at-time approach. The optimum extraction conditions obtained were as follows: isopropanol as conditioning solvent, 10 mL of sample solution at pH 2, extraction time of 30 min, stirring speed of 600 rpm, 100 μL of isopropanol as desorption solvent, desorption time of 5 min under ultrasonication, and 0.4% w/v of composite film. Under the optimized conditions, the calibration curve showed good linearity in the range of 1-500 ng/mL (r2  = 0.997-0.999), and good limits of detection (0.89-8.05 ng/mL) were obtained with good relative standard deviations of
  9. Ionic liquid-impregnated agarose film two-phase micro-electrodriven membrane extraction (IL-AF-μ-EME) for the analysis of antidepressants in water samples
    Mohamad Hanapi NS, Sanagi MM, Ismail AK, Wan Ibrahim WA, Saim N, Wan Ibrahim WN
    J Chromatogr B Analyt Technol Biomed Life Sci, 2017 Mar 01;1046:73-80.
    PMID: 28142101 DOI: 10.1016/j.jchromb.2017.01.028
    The aim of this study was to investigate and apply supported ionic liquid membrane (SILM) in two-phase micro-electrodriven membrane extraction combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) for pre-concentration and determination of three selected antidepressant drugs in water samples. A thin agarose film impregnated with 1-hexyl-3-methylimidazolium hexafluorophosphate, [C6MIM] [PF6], was prepared and used as supported ionic liquid membrane between aqueous sample solution and acceptor phase for extraction of imipramine, amitriptyline and chlorpromazine. Under the optimized extraction conditions, the method provided good linearity in the range of 1.0-1000μgL(-1), good coefficients of determination (r(2)=0.9974-0.9992) and low limits of detection (0.1-0.4μgL(-1)). The method showed high enrichment factors in the range of 110-150 and high relative recoveries in the range of 88.2-111.4% and 90.9-107.0%, for river water and tap water samples, respectively with RSDs of ≤7.6 (n=3). This method was successfully applied to the determination of the drugs in river and tap water samples. It is envisaged that the SILM improved the perm-selectivity by providing a pathway for targeted analytes which resulted in rapid extraction with high degree of selectivity and high enrichment factor.
  10. Fulltext PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae
    Spulber S, Kilian P, Wan Ibrahim WN, Onishchenko N, Ulhaq M, Norrgren L, et al.
    PLoS One, 2014;9(4):e94227.
    PMID: 24740186 DOI: 10.1371/journal.pone.0094227
    Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.
  11. Protective effect of apple mangrove Sonneratia caseolaris extract in Edwardsiella tarda-infected African catfish, Clarias gariepinus
    Aznan AS, Lee KL, Low CF, Iberahim NA, Wan Ibrahim WN, Musa N, et al.
    Fish Shellfish Immunol, 2018 Jul;78:338-345.
    PMID: 29684603 DOI: 10.1016/j.fsi.2018.04.033
    Outbreaks of edwardsiellosis have severe impact on the aquaculture production of African catfish Clarias gariepinus. In this study, feed supplemented with apple mangrove Sonneratia caseolaris extract was evaluated for its protective effect against Edwardsiella tarda infection in African catfish. Results showed an increase in growth performance and higher survival rate in the treatment groups in a dose dependent manner. Haematological analyses showed an increase in white blood cell count in the treatment groups. Histopathological analysis revealed degenerative changes and regeneration of liver tissue architecture in both the control and treatment groups. However, the presence of inflammatory cells was found exclusively in the kidney of T3 treatment group that was supplemented with the highest dose of extract at 3.17 mg/ml, which inferred the activation of immune response in the fish. Contrast to the deteriorative alteration observed in the kidney of the control group due to E. tarda infection, treatment group exhibited tissue regeneration and well-defined kidney tissue architecture at 3 dpi. Taken together, these results demonstrated that supplementation with the methanol extract of S. caseolaris possesses protective effect in African catfish against the infection of E. tarda.
  12. Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics
    Zakaria F, Akhtar MT, Wan Ibrahim WN, Abu Bakar N, Muhamad A, Shohaimi S, et al.
    Zebrafish, 2021 02;18(1):42-54.
    PMID: 33538644 DOI: 10.1089/zeb.2020.1895
    Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.
  13. Rapid Determination of Non-steroidal Anti-inflammatory Drugs in Aquatic Matrices by Two-phase Micro-electrodriven Membrane Extraction Combined with Liquid Chromatography
    Mohamad Hanapi NS, Sanagi MM, Ismail AK, Saim N, Wan Ibrahim WN, Wan Ibrahim WA, et al.
    J Chromatogr Sci, 2018 Feb 01;56(2):166-176.
    PMID: 29069322 DOI: 10.1093/chromsci/bmx092
    Two-phase micro-electrodriven membrane extraction (EME) procedure for the pre-concentration of selected non-steroidal anti-inflammatory drugs (NSAIDs) in aquatic matrices was investigated. Agarose film was used as interface between donor and acceptor phase in EME which allowed for selective extraction of the analytes prior to high performance liquid chromatography-ultraviolet detection. Charged analytes were transported from basic aqueous sample solution through agarose film into 1-octanol as an acceptor phase at 9 V potential. Response surface methodology in conjunction with the central composite design showed good correlations between extraction time and applied voltage (R2 > 0.9358). Under optimized extraction conditions, the method showed good linearity in the concentration range of 0.5-500 μg L-1 with coefficients of determination, r2≥ 0.9942 and good limits of detection (0.14-0.42 μg L-1) and limits of quantification (0.52-1.21 μg L-1). The results also showed high enrichment factors (62-86) and good relative recoveries (72-114%) with acceptable reproducibilities (RSDs ≤ 7.5% n = 3). The method was successfully applied to the determination of NSAIDs from tap water and river water samples. The proposed method proved to be rapid, simple and requires low voltage and minute amounts of organic solvent, thus environmentally friendly.
  14. Development of diarylpentadienone analogues as alpha-glucosidase inhibitor: Synthesis, in vitro biological and in vivo toxicity evaluations, and molecular docking analysis
    Abdullah MA, Lee YR, Mastuki SN, Leong SW, Wan Ibrahim WN, Mohammad Latif MA, et al.
    Bioorg Chem, 2020 11;104:104277.
    PMID: 32971414 DOI: 10.1016/j.bioorg.2020.104277
    A series of aminated- (1-9) and sulfonamide-containing diarylpentadienones (10-18) were synthesized, structurally characterized, and evaluated for their in vitro anti-diabetic potential on α-glucosidase and DPP-4 enzymes. It was found that all the new molecules were non-associated PAINS compounds. The sulfonamide-containing series (compounds 10-18) selectively inhibited α-glucosidase over DPP-4, in which compound 18 demonstrated the highest activity with an IC50 value of 5.69 ± 0.5 µM through a competitive inhibition mechanism. Structure-activity relationship (SAR) studies concluded that the introduction of the trifluoromethylbenzene sulfonamide moiety was essential for the suppression of α-glucosidase. The most active compound 18, was then further tested for in vivo toxicities using the zebrafish animal model, with no toxic effects detected in the normal embryonic development, blood vessel formation, and apoptosis of zebrafish. Docking simulation studies were also carried out to better understand the binding interactions of compound 18 towards the homology modeled α -glucosidase and the human lysosomal α -glucosidase enzymes. The overall results suggest that the new sulfonamide-containing diarylpentadienones, compound 18, could be a promising candidate in the search for a new α-glucosidase inhibitor, and can serve as a basis for further studies involving hit-to-lead optimization, in vivo efficacy and safety assessment in an animal model and mechanism of action for the treatment of T2DM patients.
  15. Fulltext Magnetic nanoparticles assisted dispersive liquid-liquid microextraction of chloramphenicol in water samples
    Saad SM, Aling NA, Miskam M, Saaid M, Mohamad Zain NN, Kamaruzaman S, et al.
    R Soc Open Sci, 2020 Apr;7(4):200143.
    PMID: 32431904 DOI: 10.1098/rsos.200143
    This work describes the development of a new methodology based on magnetic nanoparticles assisted dispersive liquid-liquid microextraction (DLLME-MNPs) for preconcentration and extraction of chloramphenicol (CAP) antibiotic residues in water. The approach is based on the use of decanoic acid as the extraction solvent followed by the application of MNPs to magnetically retrieve the extraction solvent containing the extracted CAP. The coated MNPs were then desorbed with methanol, and the clean extract was analysed using ultraviolet-visible spectrophotometry. Several important parameters, such as the amount of decanoic acid, extraction time, stirring rate, amount of MNPs, type of desorption solvent, salt addition and sample pH, were evaluated and optimized. Optimum parameters were as follows: amount of decanoic acid: 200 mg; extraction time: 10 min; stirring rate: 800 rpm; amount of MNPs: 60 mg; desorption solvent: methanol; salt: 10%; and sample pH, 8. Under the optimum conditions, the method demonstrated acceptable linearity (R2 = 0.9933) over a concentration range of 50-1000 µg l-1. Limit of detection and limit of quantification were 16.5 and 50.0 µg l-1, respectively. Good analyte recovery (91-92.7%) and acceptable precision with good relative standard deviations (0.45-6.29%, n = 3) were obtained. The method was successfully applied to tap water and lake water samples. The proposed method is rapid, simple, reliable and environmentally friendly for the detection of CAP.
  16. Evaluation of the neurotoxic effects of chronic embryonic exposure with inorganic mercury on motor and anxiety-like responses in zebrafish (Danio rerio) larvae
    Abu Bakar N, Mohd Sata NS, Ramlan NF, Wan Ibrahim WN, Zulkifli SZ, Che Abdullah CA, et al.
    Neurotoxicol Teratol, 2017 Jan-Feb;59:53-61.
    PMID: 27919701 DOI: 10.1016/j.ntt.2016.11.008
    Chronic exposure to mercury (Hg) can lead to cumulative impairments in motor and cognitive functions including alteration in anxiety responses. Although several risk factors have been identified in recent year, little is known about the environmental factors that either due exposure toward low level of inorganic mercury that may led to the developmental disorders. The present study investigated the effects of embryonic exposure of mercury chloride on motor function and anxiety-like behavior. The embryo exposed to 6 different concentrations of HgCl2 (7.5, 15, 30, 100, 125, 250nM) at 5hpf until hatching (72hpf) in a semi-static condition. The mortality rate increased in a dose dependent manner where the chronic embryonic exposure to 100nM decreased the number of tail coiling, heartbeat, and swimming activity. Aversive stimulus was used to examine the effects of 100nM interferes with the development of anxiety-related behavior. No elevation in both thigmotaxis and avoidance response of 6dpf larvae exposed with 100nM were found. Biochemical analysis showed HgCl2 exposure affects proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. These results showed that implication of HgCl2 on locomotor and biochemical defects affects motor performance and anxiety-like responses. Yet, the potential underlying mechanisms these responses need to be further investigated which is crucial to prevent potential hazards on the developing organism due to neurotoxicant exposure.
  17. Fulltext In silico studies, X-ray diffraction analysis and biological investigation of fluorinated pyrrolylated-chalcones in zebrafish epilepsy models
    Mohd Fahmi MSA, Swain P, Ramli AH, Wan Ibrahim WN, Saleh Hodin NA, Abu Bakar N, et al.
    Heliyon, 2023 Feb;9(2):e13685.
    PMID: 36852036 DOI: 10.1016/j.heliyon.2023.e13685
    Epilepsy is the third most common known brain disease worldwide. Several antiepileptic drugs (AEDs) are available to improve seizure control. However, the associated side effects limit their practical use and highlight the ongoing search for safer and effective AEDs. Eighteen newly designed fluorine-containing pyrrolylated chalcones were extensively studied in silico, synthesized, structurally analyzed by X-ray diffraction (XRD), and biologically and toxicologically tested as potential new AEDs in zebrafish epilepsy in vivo models. The results predicted that 3-(3,5-difluorophenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (compound 8) had a good drug-like profile with binding affinity to γ-aminobutyric acid receptor type-A (GABAA, -8.0 kcal/mol). This predicted active compound 8 was effective in reducing convulsive behaviour in pentylenetetrazol (PTZ)-induced larvae and hyperactive movements in zc4h2 knockout (KO) zebrafish, experimentally. Moreover, no cardiotoxic effect of compound 8 was observed in zebrafish. Overall, pyrrolylated chalcones could serve as alternative AEDs and warrant further in-depth pharmacological studies to uncover their mechanism of action.
  18. Fulltext Embryonic mercury exposure in zebrafish: Alteration of metabolites and gene expression, related to visual and behavioral impairments
    Abu Bakar N, Wan Ibrahim WN, Zulkiflli AR, Saleh Hodin NA, Kim TY, Ling YS, et al.
    Ecotoxicol Environ Saf, 2023 May;256:114862.
    PMID: 37004432 DOI: 10.1016/j.ecoenv.2023.114862
    The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl2), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.
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