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  1. Abdul Aziz AF, Mohamed AR, Murugesu S, Siti Zarina AH, Lee BN
    Med J Malaysia, 2021 07;76(4):502-509.
    PMID: 34305111
    BACKGROUND: Scalp video electroencephalography monitoring (VEM) and brain MRI sometime fail to identify the epileptogenic focus (EF) in patients with drug resistant epilepsy (DRE). 18F-FDG PET/CT has been shown to improve the detection of EF in patients but is not widely used in Malaysia. Thus, the objective of this study was to identify whether 18F-FDG PET/CT conferred an added benefit in the pre-surgical evaluation of DRE.

    METHODS: Retrospective review of 119 consecutive paediatric patients referred for 18F-FDG-PET/CT at the Department of Nuclear Medicine of the National Cancer Institute, Putrajaya. All had DRE and underwent evaluation at the Paediatric Institute, Hospital Kuala Lumpur. Visually detected areas of 18F-FDG-PET/CT hypometabolism were correlated with clinical, MRI and VEM findings.

    RESULTS: Hypometabolism was detected in 102/119 (86%) 18FFDG- PET/CT scans. The pattern of hypometabolism in 73 patients with normal MRI was focal unilobar in 16/73 (22%), multilobar unilateral in 8/73 (11%), bilateral in 27/73 (37%) and global in 5/73 (7%) of patients; whilst 17/73 (23%) showed normal metabolism. In 46 patients with lesions on MRI, 18F-FDG-PET/CT showed concordant localisation and lateralization of the EF in 30/46 (65%) patients, and bilateral or widespread hypometabolism in the rest. Addition of 18FFDG PET/CT impacted decision making in 66/119 (55%) of patients; 24/73 with non-lesional and 30/46 patients with lesional epilepsies were recommended for surgery or further surgical work up, whilst surgery was not recommended in 11/46 patients with lesional epilepsy due to bilateral or widespread hypometabolism. 25 patients subsequently underwent epilepsy surgery, with 16/25 becoming seizure free following surgery.

    CONCLUSION: 18F-FDG-PET/CT has an added benefit for the localization and lateralization of EF, particularly in patients with normal or inconclusive MRI.

  2. Murugesu, S., Khatib, A., Ibrahim, Z., Ahmed, Q. U., Uzir, B.F., Nik-Yusoff, N.I., et al.
    MyJurnal
    Clinacanthus nutans (Acanthaceae) is a local plant consumed as tisane in Indonesia and ‘ulam’ in Malaysia. This plant has been claimed for its ability to prevent many diseases including diabetes. However, the scientific proof on this claim is still lacking. Therefore, the present work study was designed to evaluate the antidiabetic potential and antioxidant capacity of C. nutans leaves extracts using in vitro bioassay tests. The 80% methanolic crude extract of this plant was further partitioned using different polarity solvents namely hexane, hexane:ethyl acetate (1:1, v/v), ethyl acetate, ethyl acetate:methanol (1:1, v/v), and methanol. All the sub-fractions were analysed for antioxidant effect via 2, 2-diphenyl-2-picrylhydrazil (DPPH) scavenging activity, ferric reducing power (FRAP) and xanthine oxidase (XO) assays followed by antidiabetic evaluation via α-glucosidase and dipeptidyl peptidase-IV (DPP-IV) inhibitory assays and glucose uptake experiment. The ethyl acetate fraction showed a good antioxidant potential while the hexane fraction exhibited high α-glucosidase and DPP-IV enzyme inhibition. The hexane fraction also improved glucose uptake in a dose-dependent manner. The present work thus provides an informative data on the potential of C. nutans to be developed as a functional food in preventing diabetes.
  3. Sarian MN, Ahmed QU, Mat So'ad SZ, Alhassan AM, Murugesu S, Perumal V, et al.
    Biomed Res Int, 2017;2017:8386065.
    PMID: 29318154 DOI: 10.1155/2017/8386065
    The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+ radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated through α-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+ radical, and FRAP assays and improved both α-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish the in vitro antioxidant and antidiabetic properties of the flavonoids.
  4. Selamat J, Rozani NAA, Murugesu S
    Molecules, 2021 Dec 14;26(24).
    PMID: 34946647 DOI: 10.3390/molecules26247565
    The authentication of food products is essential for food quality and safety. Authenticity assessments are important to ensure that the ingredients or contents of food products are legitimate and safe to consume. The metabolomics approach is an essential technique that can be utilized for authentication purposes. This study aimed to summarize food authentication through the metabolomics approach, to study the existing analytical methods, instruments, and statistical methods applied in food authentication, and to review some selected food commodities authenticated using metabolomics-based methods. Various databases, including Google Scholar, PubMed, Scopus, etc., were used to obtain previous research works relevant to the objectives. The review highlights the role of the metabolomics approach in food authenticity. The approach is technically implemented to ensure consumer protection through the strict inspection and enforcement of food labeling. Studies have shown that the study of metabolomics can ultimately detect adulterant(s) or ingredients that are added deliberately, thus compromising the authenticity or quality of food products. Overall, this review will provide information on the usefulness of metabolomics and the techniques associated with it in successful food authentication processes, which is currently a gap in research that can be further explored and improved.
  5. Murugesu S, Okayama K, Yamamoto Y, Terada K, Takahashi Y
    Epileptic Disord, 2020 Aug 01;22(4):455-461.
    PMID: 32782230 DOI: 10.1684/epd.2020.1182
    To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.
  6. Murugesu S, Ibrahim Z, Ahmed QU, Nik Yusoff NI, Uzir BF, Perumal V, et al.
    Molecules, 2018 Sep 19;23(9).
    PMID: 30235889 DOI: 10.3390/molecules23092402
    BACKGROUND: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity.

    METHODS: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS).

    RESULTS: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding.

    CONCLUSION: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.

  7. Perumal, V., Khoo, W.C., Abdul-Hamid, A., Ismail, A., Saari, K., Murugesu, S., et al.
    MyJurnal
    Momordica charantia, also known as bitter melon or ‘peria katak’ in Malaysia, is a member of the family Cucurbitaceae. Bitter melon is an excellent source of vitamins and minerals that made it extensively nutritious. Moreover, the seed, fruit and leave of the plant contain bioactive compounds with a wide range of biological activities that have been used in traditional medicines in the treatment of several diseases, including inflammation, infections, obesity and diabetes. The aim of this study was to evaluate changes in urinary metabolite profile of the normal, streptozotocin-induced type 1 diabetes and M. charantia treated diabetic rats using proton nuclear magnetic resonance (1H-NMR) -based metabolomics profiling. Study had been carried out by inducing diabetes in the rats through injection of streptozotocin, which exhibited type 1 diabetes. M. charantia extract (100 and 200 mg/kg body weight) was administrated to the streptozotocin-induced diabetic rats for one week. Blood glucose level after administration was measured to examine hypoglycemic effect of the extract. The results obtained indicated that M. charantia was effective in lowering blood glucose level of the diabetic rats. The loading plot of Partial Least Square (PLS) component 1 showed that diabetic rats had increased levels of lactate and glucose in urine whereas normal and the extract treated diabetic rats had higher levels of succinate, creatine, creatinine, urea and phenylacetylglycine in urine. While the loading plot of PLS component 2 showed a higher levels of succinate, citrate, creatine, creatinine, sugars, and hippurate in urine of normal rat compared to the extract treated diabetic rat. Administration of M. charantia extract was found to be able to regulate the altered metabolic processes. Thus, it could be potentially used to treat the diabetic patients.
    
  8. Saleh MSM, Bukhari DAM, Siddiqui MJA, Kasmuri AR, Murugesu S, Khatib A
    Nat Prod Res, 2020 May;34(9):1341-1344.
    PMID: 30678487 DOI: 10.1080/14786419.2018.1560295
    Different extraction processes were employed to extract bioactive metabolites from Salacca zalacca flesh by a range of aqueous and organic solvents. The highest extraction yield was obtained by 50% ethanol extract of SE (73.18 ± 4.35%), whereas SFE_1 showed the lowest yield (0.42 ± 0.08%). All extracts were evaluated for in vitro α-glucosidase inhibitory activity, measured by their IC50 values in comparison to that of quercetin, the positive control (IC50 = 2.7 ± 0.7 μg/mL). The lowest α-glucosidase inhibitory activity was indicated by water extract of SE (IC50 = 724.3 ± 42.9 μg/mL) and the highest activity was demonstrated by 60% ethanol extract by UAE (IC50 = 16.2 ± 2.4 μg/mL). All extracts were analysed by GC-MS and identified metabolites like carbohydrates, fatty acids, organic acids, phenolic acids, sterols and alkane-based compounds etcetera that may possess the potential as α-glucosidase inhibitor and may attribute to the α-glucosidase inhibitory activity.
  9. Murugesu S, Ibrahim Z, Ahmed QU, Uzir BF, Nik Yusoff NI, Perumal V, et al.
    J Pharm Anal, 2019 Apr;9(2):91-99.
    PMID: 31011465 DOI: 10.1016/j.jpha.2018.11.001
    The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. n-Hexane, n-hexane: ethyl acetate (1:1, v/v), ethyl acetate, ethyl acetate: methanol (1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square (PLS) statistical model was developed using the SIMCA P+14.0 software and the following four inhibitors were obtained: (1) 4,6,8-Megastigmatrien-3-one; (2) N-Isobutyl-2-nonen-6,8-diynamide; (3) 1',2'-bis(acetyloxy)-3',4'-didehydro-2'-hydro-β, ψ-carotene; and (4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase (PDB code: 3A4A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335, and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313, VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.
  10. Tan C, Selamat J, Jambari NN, Sukor R, Murugesu S, Khatib A
    Foods, 2021 Sep 14;10(9).
    PMID: 34574284 DOI: 10.3390/foods10092174
    Globally, village chicken is popular and is known as a premium meat with a higher price. Food fraud can occur by selling other chicken breeds at a premium price in local markets. This study aimed to distinguish local village chicken from other chicken breeds available in the market, namely, colored broiler (Hubbard), broiler (Cobb), and spent laying hen (Dekalb) in pectoralis major and serum under commercial conditions using an untargeted metabolomics approach. Both pectoralis major and serum were analyzed using gas chromatography-mass spectrometry (GC-MS). The principal component analysis (PCA) results distinguished four different chicken breeds into three main groups for pectoralis major and serum. A total of 30 and 40 characteristic metabolites were identified for pectoralis major and serum, respectively. The four chicken breeds were characterized by the abundance of metabolites such as amino acids (L-glutamic acid, L-threonine, L-serine, L-leucine), organic acids (L-lactic acid, succinic acid, 3-hydroxybutyric acid), sugars (D-allose, D-glucose), sugar alcohols (myo-inositol), and fatty acids (linoleic acid). Our results suggest that an untargeted metabolomics approach using GC-MS and PCA could discriminate chicken breeds for pectoralis major and serum under commercial conditions. In this study, village chicken could only be distinguished from colored broiler (Hubbard) by serum samples.
  11. Murugesu S, Selamat J, Perumal V
    Plants (Basel), 2021 Dec 14;10(12).
    PMID: 34961220 DOI: 10.3390/plants10122749
    Ficus is one of the largest genera in the plant kingdom that belongs to the Moraceae family. This review aimed to summarize the medicinal uses, phytochemistry, and pharmacological actions of two major species from this genus, namely Ficus benghalensis and Ficus religiosa. These species can be found abundantly in most Asian countries, including Malaysia. The chemical analysis report has shown that Ficus species contained a wide range of phytoconstituents, including phenols, flavonoids, alkaloids, tannins, saponins, terpenoids, glycosides, sugar, protein, essential and volatile oils, and steroids. Existing studies on the pharmacological functions have revealed that the observed Ficus species possessed a broad range of biological properties, including antioxidants, antidiabetic, anti-inflammatory, anticancer, antitumor and antiproliferative, antimutagenic, antimicrobial, anti-helminthic, hepatoprotective, wound healing, anticoagulant, immunomodulatory activities, antistress, toxicity studies, and mosquitocidal effects. Apart from the plant parts and their extracts, the endophytes residing in these host plants were discussed as well. This study also includes the recent applications of the Ficus species and their plant parts, mainly in the nanotechnology field. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PMC, Research Gate, and Scopus. Overall, the review discusses the therapeutic potentials discovered in recent times and highlights the research gaps for prospective research work.
  12. Anuar MA, Lee JX, Musa H, Abd Hadi D, Majawit E, Anandakrishnan P, et al.
    Brain Dev, 2023 Nov;45(10):547-553.
    PMID: 37661525 DOI: 10.1016/j.braindev.2023.06.004
    INTRODUCTION: Since the emergence of COVID-19, we have experienced potent variants and sub-variants of the virus with non-specific neurological manifestations. We observed a surge of the Omicron variant of COVID-19 patients with neurological manifestations where less cases of multisystem inflammatory syndrome in children (MIS-C) were reported. This article describes our experience of children with severe and rare neurological manifestations following COVID-19 infection.

    METHODS: This is a retrospective observational case series of patients under 18 years old who fulfilled the WHO COVID-19 case definition and were referred to our paediatric neurology unit at Hospital Tunku Azizah Kuala Lumpur. Their demographic data, neurological symptoms, laboratory and supporting investigations, neuroimaging, treatment and outcomes were collected and analysed.

    RESULTS: There were eleven patients with neurological manifestations who fulfilled the WHO COVID-19 case definition. Nine patients presented with seizures and/or encephalopathy, one patient with eye opsoclonus and another patient with persistent limbs myokymia. Based on the history, clinical, electrophysiological and radiological findings, two of them had febrile infection-related epilepsy syndrome, two had acute disseminated encephalomyelitis, two had acute necrotising encephalopathy of childhood, one each had hemiconvulsion-hemiplegia-epilepsy syndrome, acute encephalopathy with bilateral striatal necrosis, hemi-acute encephalopathy with biphasic seizures and reduced diffusion, infection-associated opsoclonus and myokymia.

    CONCLUSIONS: This case series highlighted a wide spectrum of neurological manifestations of COVID-19 infection. Early recognition and prompt investigations are important to provide appropriate interventions. It is essential that these investigations should take place in a timely fashion and COVID-19 quarantine period should not hinder the confirmation of various presenting clinical syndromes.

  13. Murugesu S, Khatib A, Ahmed QU, Ibrahim Z, Uzir BF, Benchoula K, et al.
    Toxicol Rep, 2019;6:1148-1154.
    PMID: 31993329 DOI: 10.1016/j.toxrep.2019.10.020
    Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows non-toxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 μg/ml, 31.25 μg/ml, 62.5 μg/ml, 125 μg/ml, 250 μg/ml and 500 μg/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 μg/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
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