Displaying publications 1 - 20 of 36 in total

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  1. Fulltext Effect of Active Site Modification towards Performance Enhancement in Biopolymer κ-Carrageenan Derivatives
    Abu Bakar MH, Azeman NH, Mobarak NN, Mokhtar MHH, A Bakar AA
    Polymers (Basel), 2020 Sep 08;12(9).
    PMID: 32911662 DOI: 10.3390/polym12092040
    This research demonstrates a one-step modification process of biopolymer carrageenan active sites through functional group substitution in κ-carrageenan structures. The modification process improves the electronegative properties of κ-carrageenan derivatives, leading to enhancement of the material's performance. Synthesized succinyl κ-carrageenan with a high degree of substitution provides more active sites for interaction with analytes. The FTIR analysis of succinyl κ-carrageenan showed the presence of new peaks at 1068 cm-1, 1218 cm-1, and 1626 cm-1 that corresponded to the vibrations of C-O and C=O from the carbonyl group. A new peak at 2.86 ppm in 1H NMR represented the methyl proton neighboring with C=O. The appearance of new peaks at 177.05 and 177.15 ppm in 13C NMR proves the substitution of the succinyl group in the κ-carrageenan structure. The elemental analysis was carried out to calculate the degree of substitution with the highest value of 1.78 at 24 h of reaction. The XRD diffractogram of derivatives exhibited a higher degree of crystallinity compared to pristine κ-carrageenan at 23.8% and 9.2%, respectively. Modification of κ-carrageenan with a succinyl group improved its interaction with ions and the conductivity of the salt solution compared to its pristine form. This work has a high potential to be applied in various applications such as sensors, drug delivery, and polymer electrolytes.
  2. Factors associated with anxiety among elderly hypertensive in primary care setting
    Ismail Z, Mohamad M, Isa MR, Fadzil MA, Yassin SM, Ma KT, et al.
    J Ment Health, 2015 Feb;24(1):29-32.
    PMID: 25358109 DOI: 10.3109/09638237.2014.971148
    BACKGROUND: There is increasing evidence showing that anxiety is associated with morbidity in the older age group. Factors contributing to anxiety may vary among different diseases and settings.
    AIMS: The aim of this study was to determine the factors associated with anxiety symptoms among elderly hypertensive at the primary care level.
    METHODS: A cross-sectional study and face-to-face interviews using Hospital Anxiety and Depression Scale (HADS) were conducted among elderly hypertensive.
    RESULTS: The mean (SD) age of subjects was 68.8 (6.76) years and comprised of 49.5% and 50.5% of males and females, respectively. The majority of respondents were Malays (76.1%), followed by Chinese (14.3%), and Indians (9.5%). The mean (SD) duration of hypertension was 8.44 (7.29) years and the prevalence of anxiety symptoms was 13.3% (95% CI: 9.9, 16.7). Multiple logistic regression analysis showed that elderly hypertensive with a past history of stroke (adjusted OR: 4.472; 95% CI: 1.754, 11.405; p = 0.002) and depression (adjusted OR: 3.715; 95% CI: 2.009, 6.872; p 
  3. Fulltext Detection of dengue using PAMAM dendrimer integrated tapered optical fiber sensor
    Mustapha Kamil Y, Al-Rekabi SH, Yaacob MH, Syahir A, Chee HY, Mahdi MA, et al.
    Sci Rep, 2019 09 17;9(1):13483.
    PMID: 31530893 DOI: 10.1038/s41598-019-49891-7
    The exponential escalation of dengue cases has indeed become a global health crisis. This work elaborates on the development of a biofunctionalized tapered optical fiber (TOF) based sensor with the integration of polyamidoamine (PAMAM) dendrimer for the detection of dengue E protein. The dimension of the TOF generated an evanescent field that was sensitive to any changes in the external medium while the integration of PAMAM promoted more adhesion of bio-recognition molecules; anti-DENV II E protein antibodies; that were complementary to the targeted protein. This in return created more active sites for the absorption of DENV II E proteins onto the tapered region. The resolution and detection limit of the sensor are 19.53 nm/nM and 1 pM, respectively with Kd = 1.02 × 10-10 M.
  4. Chemical constituents from the stem barks of Calophyllum recurvatum P.F. Stevens and Calophyllum andersonii P.F. Stevens, and their in-vitro hepatotoxic activity
    Firouz NS, Karunakaran T, Mokhtar N, Santhanam R, Jong VYM, Abu Bakar MH
    Nat Prod Res, 2024 Jan 22.
    PMID: 38247357 DOI: 10.1080/14786419.2024.2305222
    Bioactive phenolics can be found in abundance in Calophyllum species. Phytochemical studies are carried out on the stem bark of Calophyllum recurvatum and Calophyllum andersonii, which has led to the isolation and elucidation of phytochemicals, thwaitesixanthone (1), teysmanone A (2), soulattrolide (3), calanone (4), isocalanone (5) and friedelin (6), respectively. The cytotoxic activities of compounds (2), (3), (4) and (5) as well as plant extracts were tested against HeLa Chang liver, HepG2 and HL-7702 cell lines. Phenylpyranocoumarins, teysmanone A (2) and soulattrolide (3) portrayed appreciable cytotoxicity activities at 42.57 ± 1.20 and 34.53 ± 3.41 µg/mL, respectively against HepG2 cell line comparable to the positive control, curcumin. Meanwhile, n-hexane extract from C. recurvatum exhibited cytotoxicity with the IC50 value of 36.43 ± 0.64 and 26.25 ± 4.83 µg/mL against HeLa Chang liver and HepG2 cell lines. All the tested compounds and plant extracts displayed non-cytotoxic properties on HL-7702 cell line.
  5. Fulltext Transcriptome Analysis of Pseudomonas aeruginosa Biofilm Following the Exposure to Malaysian Stingless Bee Honey
    Seder N, Abu Bakar MH, Abu Rayyan WS
    Adv Appl Bioinform Chem, 2021;14:1-11.
    PMID: 33488102 DOI: 10.2147/AABC.S292143
    Introduction: Malaysian stingless bee honey (Trigona) has been aroused as a potential antimicrobial compound with antibiofilm activity. The capability of the gram-negative bacillus P. aeruginosa to sustain a fatal infection is encoded in the bacterium genome.

    Methods: In the current study, a transcriptome investigation was performed to explore the mechanism underlying the biofilm dispersal of P. aeruginosa after the exposure to Trigona honey.

    Results: Microarray analysis of the Pseudomonas biofilm treated by 20% Trigona honey has revealed a down-regulation of 3478 genes among the 6085 screened genes. Specifically, around 13.5% of the down-regulated genes were biofilm-associated genes. The mapping of the biofilm-associated pathways has shown an ultimate decrease in the expression levels of the D-GMP signaling pathway and diguanylate cyclases (DGCs) genes responsible for c-di-GMP formation.

    Conclusion: We predominantly report the lowering of c-di-GMP through the down-regulation of DGC genes as the main mechanism of biofilm inhibition by Trigona honey.

  6. Fulltext Optical-based sensors for monitoring corrosion of reinforcement rebar via an etched cladding Bragg grating
    Abu Hassan MR, Abu Bakar MH, Dambul K, Adikan FR
    Sensors (Basel), 2012;12(11):15820-6.
    PMID: 23202233 DOI: 10.3390/s121115820
    In this paper, we present the development and testing of an optical-based sensor for monitoring the corrosion of reinforcement rebar. The testing was carried out using an 80% etched-cladding Fibre Bragg grating sensor to monitor the production of corrosion waste in a localized region of the rebar. Progression of corrosion can be sensed by observing the reflected wavelength shift of the FBG sensor. With the presence of corrosion, the etched-FBG reflected spectrum was shifted by 1.0 nm. In addition, with an increase in fringe pattern and continuously, step-like drop in power of the Bragg reflected spectrum was also displayed.
  7. Nitrate Classification Based on Optical Absorbance Data Using Machine Learning Algorithms for a Hydroponics System
    Sulaiman R, Azeman NH, Abu Bakar MH, Ahmad Nazri NA, Masran AS, Ashrif A Bakar A
    Appl Spectrosc, 2023 Feb;77(2):210-219.
    PMID: 36348500 DOI: 10.1177/00037028221140924
    Nutrient solution plays an essential role in providing macronutrients to hydroponic plants. Determining nitrogen in the form of nitrate is crucial, as either a deficient or excessive supply of nitrate ions may reduce the plant yield or lead to environmental pollution. This work aims to evaluate the performance of feature reduction techniques and conventional machine learning (ML) algorithms in determining nitrate concentration levels. Two features reduction techniques, linear discriminant analysis (LDA) and principal component analysis (PCA), and seven ML algorithms, for example, k-nearest neighbors (KNN), support vector machine, decision trees, naïve bayes, random forest (RF), gradient boosting, and extreme gradient boosting, were evaluated using a high-dimensional spectroscopic dataset containing measured nitrate-nitrite mixed solution absorbance data. Despite the limited and uneven number of samples per class, this study demonstrated that PCA outperformed LDA on the high-dimensional spectroscopic dataset. The classification accuracy of ML algorithms combined with PCA ranged from 92.7% to 99.8%, whereas the classification accuracy of ML algorithms combined with LDA ranged from 80.7% to 87.6%. The PCA with the RF algorithm exhibited the best performance with 99.8% accuracy.
  8. Phytoconstituents of Endiandra kingiana; antidiabetic effects and molecular docking studies on alpha-amylase and alpha-glucosidase
    Tanazi NNH, Aziz AN, Azmi MN, Abu Bakar MH, Hassim MFN, Wahab NHA, et al.
    Nat Prod Res, 2023 Nov 27.
    PMID: 38009213 DOI: 10.1080/14786419.2023.2283759
    Phytochemical investigation on the bark of E. kingiana plant afforded ten compounds, including six polyketides namely kingianin A 1, kingianin B 2, kingianin E 3, kingianin F 4, kingianin K 5 and kingianin L 6, three endiandric acids; kingianic acid A 7, tsangibeilin B 8 and endiandric acid M 9, and one sesquiterpene; daibuoxide 10. All compounds were separated as racemic mixture by recycling high-performance liquid chromatography (RHPLC), except for daibuoxide. Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. This is the first report on the presence of the sesquiterpene; daibuoxide in Endiandra genus. In vitro enzymatic bio-evaluation of the isolated compounds against α-amylase and α-glucosidase showed that 4 demonstrated the best α-amylase and α-glucosidase inhibitory activity with IC50 values of 181.54 ± 6.27 µg/mL and 237.87 ± 0.07 µg/mL, respectively. In addition, molecular docking analysis confirmed the α-amylase and α-glucosidase inhibitory activities demonstrated by 4.
  9. Synthesis, biological evaluation, and molecular modelling of novel quinoxaline-isoxazole hybrid as anti-hyperglycemic
    Phongphane L, Mohd Radzuan SN, Abu Bakar MH, Che Omar MT, Supratman U, Harneti D, et al.
    Comput Biol Chem, 2023 Oct;106:107938.
    PMID: 37542847 DOI: 10.1016/j.compbiolchem.2023.107938
    In our effort to develop potent anti-hyperglycemic compounds with inhibitory activity against α-amylase and α-glucosidase, a series of novel quinoxaline-isoxazole moieties were synthesized. The novel quinoxaline-isoxazole derivatives were assessed in vitro for their anti-hyperglycemic activities on α-amylase and α-glucosidase inhibitions. The results revealed promising IC50 values compared to acarbose as a positive control for α-amylase and α-glucosidase. Among them, N-Ethyl-7-chloro-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5b showed dual inhibitory with IC50 of 24.0 µM for α-amylase and 41.7 µM for α-glucosidase. In addition, N-Ethyl-7-methoxy-3-((3-(2-chlorophenyl)isoxazol-5-yl)methoxy)quinoxalin-2-amine 5j also had dual bioactivities against α-amylase and α-glucosidase with IC50 of 17.0 and 40.1 µM, respectively. Nevertheless, two more compounds N-Ethyl-7-cyano-3-((3-phenylisoxazol-5-yl)methoxy)quinoxaline-2-amine 5e showed strong mono-inhibition for α-glucosidase with IC50 of 16.6 µM followed by N-Ethyl-7-methoxy-3-((3-phenylisoxazol-5-yl)methoxy)quinoxalin-2-amine 5 f with IC50 of 18.6 µM. The molecular docking study for α-glucosidase inhibitor provided the binding energy ranging from 8.3 to 9.1 kcal/mol and α-amylase inhibitor showed the binding energy score at 8.4 and 8.5 kcal/mol. The dual inhibitions nature of 5b and 5j were further analyzed and confirmed via molecular dynamics including the stability of the compound, interaction energy, binding free energy, and the interaction residue analysis using the MM-GBSA approach. The results showed that compound 5j was the most potent compound. Lastly, the drug-likeness properties were also evaluated with all synthesized compounds 5a-5j and the results reveal that all potent compounds meet Lipinski's rules of five.
  10. Fulltext Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors
    Mohd Radzuan SN, Phongphane L, Abu Bakar MH, Che Omar MT, Nor Shahril NS, Supratman U, et al.
    RSC Adv, 2024 Feb 29;14(11):7684-7698.
    PMID: 38444963 DOI: 10.1039/d3ra08642a
    New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
  11. Chemodiverse monoterpene indole alkaloids from Kopsia teoi, inhibitory potential against α-amylase, and their molecular docking studies
    Muhammad MT, Beniddir MA, Phongphane L, Abu Bakar MH, Hussin MH, Awang K, et al.
    Fitoterapia, 2024 Apr;174:105873.
    PMID: 38417682 DOI: 10.1016/j.fitote.2024.105873
    Diabetes mellitus stands as a metabolic ailment marked by heightened blood glucose levels due to inadequate insulin secretion. The primary aims of this investigative inquiry encompassed the isolation of phytochemical components from the bark of Kopsia teoi, followed by the assessment of their α-amylase inhibition. The phytochemical composition of the K. teoi culminated in the discovery of a pair of new indole alkaloids; which are 16-epi-deacetylakuammiline N(4)-methylene chloride (akuammiline) (1), and N(1)-methoxycarbonyl-11-methoxy-12-hydroxy-Δ14-17-kopsinine (aspidofractinine) (2), together with five known compounds i.e. kopsiloscine G (aspidofractinine) (3), akuammidine (sarpagine) (4), leuconolam (aspidosperma) (5), N-methoxycarbonyl-12-methoxy-Δ16, 17-kopsinine (aspidofractinine) (6), and kopsininate (aspidofractinine) (7). All compounds were determined via spectroscopic analyses. The in vitro evaluation against α-amylase showed good inhibitory activities for compounds 5-7 with the inhibitory concentration (IC50) values of 21.7 ± 1.2, 34.1 ± 0.1, and 30.0 ± 0.8 μM, respectively compared with the reference acarbose (IC50 = 34.4 ± 0.1 μM). The molecular docking outputs underscored the binding interactions of compounds 5-7 ranging from -8.1 to -8.8 kcal/mol with the binding sites of α-amylase. Consequently, the outcomes highlighted the anti-hyperglycemic attributes of isolates from K. teoi.
  12. Hybrid ensemble-based machine learning model for predicting phosphorus concentrations in hydroponic solution
    Sulaiman R, Azeman NH, Mokhtar MHH, Mobarak NN, Abu Bakar MH, Bakar AAA
    Spectrochim Acta A Mol Biomol Spectrosc, 2024 Jan 05;304:123327.
    PMID: 37708761 DOI: 10.1016/j.saa.2023.123327
    Accurate, label-free, and rapid methods for measuring phosphorus concentrations are essential in a hydroponic system, as excessive or insufficient phosphorus levels can adversely affect plant growth, human health, and environmental sustainability. In this study, we demonstrate the advantages of hybrid machine learning models compared to single machine learning models in predicting phosphorus concentration based on the absorbance dataset. Three machine learning classifiers- Random Forest (RF), Support Vector Machine (SVM), and K-Nearest Neighbors (KNN)- were employed as bases for single and hybrid machine learning models. Three ensemble techniques (voting, bagging, and stacking) were used to hybridize the classifiers. Among the single models, KNN demonstrated the fastest computational time of 18.07 s, while SVM achieved the highest accuracy of 99.6%. The hybrid SVM/KNN model using a voting classifier showed a significant increase in accuracy for KNN with only a slight increase in computational time. Bagging techniques increased the accuracy but at a longer computational time. The stacking technique, which combined SVM, KNN, and RF, achieved the highest accuracy of 99.73% with a short computational time of 36.18 s compared to the bagging and voting technique. This study demonstrates that the machine learning method can effectively distinguish phosphorus concentrations. In contrast, hybrid machine learning techniques can improve accuracy for predicting phosphorus without using labels, despite requiring longer computational time.
  13. Fulltext Succinyl-κ-carrageenan Silver Nanotriangles Composite for Ammonium Localized Surface Plasmon Resonance Sensor
    Abu Bakar MH, Azeman NH, Mobarak NN, Ahmad Nazri NA, Tengku Abdul Aziz TH, Md Zain AR, et al.
    Polymers (Basel), 2022 Jan 14;14(2).
    PMID: 35054734 DOI: 10.3390/polym14020329
    This research investigates the physicochemical properties of biopolymer succinyl-κ-carrageenan as a potential sensing material for NH4+ Localized Surface Plasmon Resonance (LSPR) sensor. Succinyl-κ-carrageenan was synthesised by reacting κ-carrageenan with succinic anhydride. FESEM analysis shows succinyl-κ-carrageenan has an even and featureless topology compared to its pristine form. Succinyl-κ-carrageenan was composited with silver nanoparticles (AgNP) as LSPR sensing material. AFM analysis shows that AgNP-Succinyl-κ-carrageenan was rougher than AgNP-Succinyl-κ-carrageenan, indicating an increase in density of electronegative atom from oxygen compared to pristine κ-carrageenan. The sensitivity of AgNP-Succinyl-κ-carrageenan LSPR is higher than AgNP-κ-carrageenan LSPR. The reported LOD and LOQ of AgNP-Succinyl-κ-carrageenan LSPR are 0.5964 and 2.7192 ppm, respectively. Thus, AgNP-Succinyl-κ-carrageenan LSPR has a higher performance than AgNP-κ-carrageenan LSPR, broader detection range than the conventional method and high selectivity toward NH4+. Interaction mechanism studies show the adsorption of NH4+ on κ-carrageenan and succinyl-κ-carrageenan were through multilayer and chemisorption process that follows Freundlich and pseudo-second-order kinetic model.
  14. Fulltext Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells
    Abu Bakar MH, Cheng KK, Sarmidi MR, Yaakob H, Huri HZ
    Molecules, 2015 May 07;20(5):8242-69.
    PMID: 25961164 DOI: 10.3390/molecules20058242
    Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA) in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.
  15. Phenolics and triterpenoids from stem bark of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens and their cytotoxic activities
    Mokhtar N, Karunakaran T, Santhanam R, Abu Bakar MH, Jong VYM
    Nat Prod Res, 2024;38(5):873-878.
    PMID: 37005001 DOI: 10.1080/14786419.2023.2196075
    Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity.
  16. Phytochemicals from the Stem Bark of Calophyllum havilandii P. F. Stevens and their Biological Activities
    Zailan AAD, Karunakaran T, Santhanam R, Suriaty Yaakop A, Mohan S, Abu Bakar MH, et al.
    Chem Biodivers, 2024 Mar;21(3):e202301936.
    PMID: 38268343 DOI: 10.1002/cbdv.202301936
    The genus Calophyllum from the family Calophyllaceae has been extensively investigated in the past due to its rich source of bioactive phenolics such as coumarins, chromanones, and xanthones. In this study, phytochemical investigation on the stem bark of Calophyllum havilandii has afforded a new 4-propyldihydrocoumarin derivative, havilarin (1) together with calolongic acid (2), caloteysmannic acid (3), isocalolongic acid (4), euxanthone (5), and β-sitosterol (6). The chemical structure of compound 1 was elucidated and established based on detailed spectroscopic techniques, including MS, IR, UV, 1D and 2D NMR. The results of anti-bacillus study indicated that the chloroform extract showed promising activities with MIC value ranging between 0.5 to 1 μg/mL on selected bacillus strains. Besides, the plant extracts and compounds 1-4 were assessed for their cytotoxicity potential on HL-7702 cell line. All the tested plant extracts and respective chemical constituents displayed non-cytotoxic activity on HL-7702 cell line.
  17. Celastrol attenuates high-fructose diet-induced inflammation and insulin resistance via inhibition of 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues
    Abu Bakar MH, Mohamad Khalid MSF, Nor Shahril NS, Shariff KA, Karunakaran T
    Biofactors, 2022 Jan;48(1):111-134.
    PMID: 34676604 DOI: 10.1002/biof.1793
    High fructose consumption has been linked to low-grade inflammation and insulin resistance that results in increased intracellular 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)-induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co-administrations upon HFrD in rats and evaluate its potential to modulate 11β-HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor-kappa B (NF-κB)-driven inflammation, reduced c-Jun N-terminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β-HSD1 towards oxidoreductase activity (IC50 value = 4.3 nM) in comparison to other HSD-related enzymes. Inhibition of 11β-HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein expressions of glucocorticoid receptor. In conclusion, our results underscore the most likely conceivable mechanisms exhibited by celastrol against HFrD-induced metabolic dysregulations mainly through attenuating inflammation and insulin resistance, at least via specific inhibitions on 11β-HSD1 activity in adipose tissues.
  18. Celastrol attenuates inflammatory responses in adipose tissues and improves skeletal muscle mitochondrial functions in high fat diet-induced obese rats via upregulation of AMPK/SIRT1 signaling pathways
    Abu Bakar MH, Shariff KA, Tan JS, Lee LK
    Eur J Pharmacol, 2020 Sep 15;883:173371.
    PMID: 32712089 DOI: 10.1016/j.ejphar.2020.173371
    Accumulating evidence indicates that adipose tissue inflammation and mitochondrial dysfunction in skeletal muscle are inextricably linked to obesity and insulin resistance. Celastrol, a bioactive compound derived from the root of Tripterygium wilfordii exhibits a number of attributive properties to attenuate metabolic dysfunction in various cellular and animal disease models. However, the underlying therapeutic mechanisms of celastrol in the obesogenic environment in vivo remain elusive. Therefore, the current study investigated the metabolic effects of celastrol on insulin sensitivity, inflammatory response in adipose tissue and mitochondrial functions in skeletal muscle of the high fat diet (HFD)-induced obese rats. Our study revealed that celastrol supplementation at 3 mg/kg/day for 8 weeks significantly reduced the final body weight and enhanced insulin sensitivity of the HFD-fed rats. Celastrol noticeably improved insulin-stimulated glucose uptake activity and increased expression of plasma membrane GLUT4 protein in skeletal muscle. Moreover, celastrol-treated HFD-fed rats showed attenuated inflammatory responses via decreased NF-κB activity and diminished mRNA expression responsible for classically activated macrophage (M1) polarization in adipose tissues. Significant improvement of muscle mitochondrial functions and enhanced antioxidant defense machinery via restoration of mitochondrial complexes I + III linked activity were effectively exhibited by celastrol treatment. Mechanistically, celastrol stimulated mitochondrial biogenesis attributed by upregulation of the adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) signaling pathways. Together, these results further demonstrate heretofore the conceivable therapeutic mechanisms of celastrol in vivo against HFD-induced obesity mediated through attenuation of inflammatory response in adipose tissue and enhanced mitochondrial functions in skeletal muscle.
  19. Fulltext The role of lycopene for the amelioration of glycaemic status and peripheral antioxidant capacity among the Type II diabetes mellitus patients: a case-control study
    Leh HE, Mohd Sopian M, Abu Bakar MH, Lee LK
    Ann Med, 2021 12;53(1):1059-1065.
    PMID: 34180336 DOI: 10.1080/07853890.2021.1943515
    BACKGROUND: The use of lycopene as a complementary medicine for Type II diabetes mellitus (T2DM) is limited and controversial. This study evaluated the effect of lycopene intake on the changes of glycaemic status and antioxidant capacity among the T2DM patients.

    PATIENTS AND METHODS: This case-control study involved the participation of 87 patients and 122 healthy individuals. Lycopene intake was assessed by using a food frequency questionnaire. The peripheral antioxidant capacity among the T2DM patients was evaluated. Glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were measured as indications of glycaemic status.

    RESULTS: Peripheral antioxidant capacity was significantly lower in the T2DM group. Direct positive correlations were found between the lycopene intake and peripheral antioxidant level among the T2DM patients. Contrarily, HbA1c and FPG levels decreased significantly with the higher lycopene intake.

    CONCLUSIONS: T2DM patients with a higher lycopene intake showed a greater peripheral antioxidant capacity and better glycaemic control. Lycopene may act to ameliorate oxidative stress and improve the pathophysiology of T2DM.

  20. Construction of microbial electrodialysis cells equipped with internal proton migration pathways: Enhancement of wastewater treatment, desalination, and hydrogen production
    Salehmin MNI, Hil Me MF, Daud WRW, Mohd Yasin NH, Abu Bakar MH, Sulong AB, et al.
    Sci Total Environ, 2023 Jan 10;855:158527.
    PMID: 36096221 DOI: 10.1016/j.scitotenv.2022.158527
    Microbial electrodialysis cells (MEDCs) offer simultaneous wastewater treatment, water desalination, and hydrogen production. In a conventional design of MEDCs, the overall performance is retarded by the accumulation of protons on the anode due to the integration of an anion exchange membrane (AEM). The accumulation of protons reduces the anolyte pH to become acidic, affecting the microbial viability and thus limiting the charge carrier needed for the cathodic reaction. This study has modified the conventional MEDC with an internal proton migration pathway, known as the internal proton migration pathway-MEDC (IP-MEDC). Simulation tests under abiotic conditions demonstrated that the pH changes in the anolyte and catholyte of IP-MEDC were smaller than the pH changes in the anolyte and catholyte without the proton pathways. Under biotic conditions, the performance of the IP-MEDC agreed well with the simulation test, showing a significantly higher chemical oxygen demand (COD) removal rate, desalination rate, and hydrogen production than without the migration pathway. This result is supported by the lowest charge transfer resistance shown by EIS analysis and the abundance of microbes on the bioanode through field emission scanning electron microscopy (FESEM) observation. However, hydrogen production was diminished in the second-fed batch cycle, presumably due to the active diffusion of high Cl¯ concentrations from desalination to the anode chamber, which was detrimental to microbial growth. Enlarging the anode volume by threefold improved the COD removal rate and hydrogen production rate by 1.7- and 3.4-fold, respectively, owing to the dilution effect of Cl¯ in the anode. This implied that the dilution effect satisfies both the microbial viability and conductivity. This study also suggests that the anolyte and catholyte replacement frequencies can be reduced, typically at a prolonged hydraulic retention time, thus minimizing the operating cost (e.g., solution pumping). The use of a high concentration of NaCl (35 g L-1) in the desalination chamber and catholyte provides a condition that is close to practicality.
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