Displaying publications 41 - 60 of 129 in total

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  1. Fulltext IGF2BP2 alternative variants associated with glutamic acid decarboxylase antibodies negative diabetes in Malaysian subjects
    Salem SD, Saif-Ali R, Ismail IS, Al-Hamodi Z, Poh R, Muniandy S
    PLoS One, 2012;7(9):e45573.
    PMID: 23029108 DOI: 10.1371/journal.pone.0045573
    The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects.
  2. Fulltext KCNQ1 haplotypes associate with type 2 diabetes in Malaysian Chinese Subjects
    Saif-Ali R, Ismail IS, Al-Hamodi Z, Al-Mekhlafi HM, Siang LC, Alabsi AM, et al.
    Int J Mol Sci, 2011;12(9):5705-18.
    PMID: 22016621 DOI: 10.3390/ijms12095705
    The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10(-5); OR = 1.9, P = 5.2 × 10(-5); OR = 1.9, P = 7.8 × 10(-5), respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10(-11)). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.
  3. Fulltext Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects
    Al-Hamodi Z, Ismail IS, Saif-Ali R, Ahmed KA, Muniandy S
    Cardiovasc Diabetol, 2011;10:23.
    PMID: 21414238 DOI: 10.1186/1475-2840-10-23
    Increased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1 and tPA activities and antigens in Malaysian T2D and normal subjects.
  4. Fulltext Use of glycated hemoglobin (HbA(1C)) and impaired glucose tolerance in the screening of undiagnosed diabetes in the Malaysian population
    Qvist R, Ismail IS, Chinna K, Muniandy S
    Indian J Clin Biochem, 2008 Jul;23(3):246-9.
    PMID: 23105763 DOI: 10.1007/s12291-008-0055-x
    Although HbA(1C) is widely accepted as a useful index of mean blood glucose in type 2 diabetic patients its usefulness as screening test for diabetes has been controversial. The present study was undertaken to determine whether the level of HbA(1C) predicted diabetes in a prediabetic group of subjects. Plasma lipids, oral glucose tolerance, HbA(1C) was determined in 90 normal control subjects, 57 offspring of one type 2 diabetes mellitus parent and 11 diagnosed type 2 diabetes mellitus individuals. The mean age of participants was 44.5 yrs (not significantly different amongst the three groups) and the mean body mass index was 26.8 (not significantly different amongst the three groups). Two hours after a 75 g glucose challenge, the offspring had a significantly higher plasma glucose level (mean = 7.1 mmol/L, p value = 0.002) than the normals. Similarly the HbA(1C) values were higher in the offspring than in the normals (mean = 5.78%, p value = 0.016). Besides the significantly higher values for oral glucose tolerance test and HbA(1C), the diabetics also were significantly higher for triglycerides (mean = 2.25mmol/L), total cholesterol (mean = 6.24mmol/L) and systolic blood pressure (mean = 138.45mm Hg) than the offspring (P value = 0.031, 0.006, 0.010) and the normals (P value = 0.026, 0.018, 0.002) respectively. The mean values of diastolic blood pressure, LDL cholesterol and HDL cholesterol were not significantly different amongst the three groups.
    Study site: Diabetic clinic, University of Malaya Medical centre (UMMC), Kuala Lumpur, Malaysia
  5. Fulltext Effect of plasminogen activator inhibitor-1 and tissue plasminogen activator polymorphisms on susceptibility to type 2 diabetes in Malaysian subjects
    Al-Hamodi Z, Saif-Ali R, Ismail IS, Ahmed KA, Muniandy S
    J Biomed Biotechnol, 2012;2012:234937.
    PMID: 22577291 DOI: 10.1155/2012/234937
    Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR = 2.35, P = 0.045; OR = 1.67, P = 0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR = 3.32, P = 0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.
  6. The ribosomal protein L19 mRNA is induced by copper exposure in the swordtail fish, Xiphophorus helleri
    Aliza D, Tey CL, Ismail IS, Kuah MK, Shu-Chien AC, Muhammad TS
    Mol Biol Rep, 2012 Apr;39(4):4823-9.
    PMID: 21956757 DOI: 10.1007/s11033-011-1275-3
    Teleosts are useful vertebrate model species for understanding copper toxicity due to the dual entry route for copper intake via the gills and intestine. In this present study, we utilized the differential display reverse transcription-polymerase chain reaction to isolate potential novel hepatic genes induced by sublethal copper exposure in the freshwater swordtail fish, Xiphophorus helleri. Full length cloning of a cDNA fragment induced by copper exposure to 1 μg/ml during 24 h resulted in the positive identification of a hepatic ribosomal protein L19 (RPL19) gene. Further characterization of this gene revealed that its transcriptional expression was dependent on dosage and time of copper exposure. This study describes for the first time the involvement of RPL19 in copper toxicity, probably as a result of increase in ribosome synthesis rate to support activities such as cellular protein translation, transcriptional activation and mRNA stabilization during sublethal copper exposure.
  7. Chrotacumines A-D, chromone alkaloids from Dysoxylum acutangulum
    Ismail IS, Nagakura Y, Hirasawa Y, Hosoya T, Lazim MI, Lajis NH, et al.
    J Nat Prod, 2009 Oct;72(10):1879-83.
    PMID: 19757855 DOI: 10.1021/np9003849
    Four new chromone alkaloids, chrotacumines A-D (1-4), consisting of a 5,7-dihydroxy-2-methylchromone, an N-Me piperidine ring, and an ester side chain were isolated from Dysoxylum acutangulum, and their structures including absolute configurations were elucidated on the basis of spectroscopic data interpretation including 2D NMR, CD spectra, and X-ray analysis. The known compound rohitukine (5) showed moderate cytotoxicity against human HL-60 promyelocytic leukemia and HCT-116 colon cancer cells.
  8. A new coumarin from stem bark of Calophyllum wallichianum
    Tee KH, Ee GCL, Ismail IS, Karunakaran T, Teh SS, Jong VYM, et al.
    Nat Prod Res, 2018 Nov;32(21):2565-2570.
    PMID: 29355031 DOI: 10.1080/14786419.2018.1428588
    A phytochemical study carried out on the plant, Calophyllum wallichianum has led to the isolation of a new coumarin, wallimarin T (1) and a known coumarin, calanolide E (2) along with two common triterpenes, friedelin (3) and stigmasterol (4). The structures of these compounds were elucidated with the aid of spectroscopic analyses such as FT-IR, GC-MS, and NMR. MIC assay against the Bacillus bacteria were conducted on the extracts and this gave MIC values ranging from 0.313 to 1.25 mg/mL. Compound 2 was weakly inhibitory towards the Bacilli strains with MIC values ranging from 0.25-0.50 mg/mL. Wallimarin T (1) was not active towards all four bacteria. Overall, the extracts exhibited weak bactericidal properties whereas compound 2 was not bactericidal on the tested bacteria. The hexane and chloroform extracts of the plant were found to be inhibitors to the growth of Bacillus megaterium, Bacillus cereus, Bacillus pumilus and Bacillus subtilis.
  9. Fulltext Extraction and Characterization of Organ Components of the Malaysian Sea Cucumber Holothuria leucospilota Yielded Bioactives Exhibiting Diverse Properties
    Ceesay A, Nor Shamsudin M, Aliyu-Paiko M, Ismail IS, Nazarudin MF, Mohamed Alipiah N
    Biomed Res Int, 2019;2019:2640684.
    PMID: 31119160 DOI: 10.1155/2019/2640684
    The aim of the present study was to extract and characterize bioactive components from separate body organs of Holothuria leucospilota. Preliminary qualitative assessment of the crude extracts was positive for phenols, terpenoids, carbohydrates, flavonoids, saponins, glycosides, cardiac glycosides, steroids, phlobatannins, and tannins in all body organs evaluated. Phenolics were the most abundant group of bioactives accounting for approximately 80%. The extraction solvent mixtures that yielded most compounds evaluated were methanol/acetone (3:1, v:v) and methanol/distilled water (3:1, v:v). In other analyses, GC-MS data revealed diverse metabolic and biologically active compounds, where those in high concentrations included 2-Pentanone, 4-hydroxy-4-methyl- among the ketones; phenol- 2,4-bis(1,1-dimethylethyl)-, a phenol group; and 2-Chlorooctane, a hydrocarbon. Among FA and their methyl/ethyl esters, n-hexadecanoic acid, 5,8,11,14-eicosatetraenoic acid ethyl ester (arachidonic acid), and 5,8,11,14,17-eicosapentaenoic acid methyl ester (EPA) were among the most abundant FAMEs accounting for approximately 50% of the subgroups measured. Data from GC-FID analysis revealed methyl laurate (C12:0), methyl myristate (C14:0), methyl palmitate (C16:0), and methyl stearate (18:0) methyl esters as the most abundant saturated FA, whereas cis-9-oleic methyl ester (C18:1) and methyl linoleate (C18:2) were found as the major monounsaturated FA and PUFA FAMEs, respectively, in the body wall of the species. Taken together, the extraction and characterization of different categories of metabolically and biologically active compounds in various organ extracts of H. leucospilota suggest that the species is potentially a rich source of cholesterol-lowering, antioxidant, antimicrobial, and anticancer agents. These substances are known to benefit human health and assist in disease prevention. These findings justify the use of sea cucumbers in traditional folklore medication and the current interest and attention focused on the species to mine for bioactives in new drugs research.
  10. Antioxidant and α-Glucosidase Inhibitory Constituents from Hornstedtia Species of Malaysia
    Hashim SE, Sirat HM, Yen KH, Ismail IS, Matsuki SN
    Nat Prod Commun, 2015 Sep;10(9):1561-3.
    PMID: 26594759
    Seven compounds were isolated from the n-hexane and chloroform extracts of the flowers and leaves of four Hornstedtia species and their structures were identified using spectroscopic techniques as 3,7,4'-trimethylkaempferol (1), 3,7-dimethylkaempferol (2), 7,4'-dimethylkaempferol (3), 3,5-dimethylkaempferol (4), 3-methylkaempferol (5), stigmast-4-en-3-one (6), and 6-hydroxy-stigmast-4-en-3-one (7). Compounds 1 to 7 were isolated from these species for the first time. They were assayed for free radical scavenging and α-glucosidase inhibition activities. The DPPH assay showed that 3-methylkaempferol (5) was the most potent antioxidant agent with an IC50 value 78.6 µM, followed by 7,4'-dimethylkaempferol (3) (IC50 = 86.1 µM). For α-glucosidase inhibition activity, 3-methylkaempferol (5) exhibited significant inhibitory activity with an IC50 value 21.0 µM. The present study revealed that Hornstedtia species have potential activities as antioxidant and α-glucosidase inhibitors.
  11. Cytotoxic xanthones isolated from Calophyllum depressinervosum and Calophyllum buxifolium with antioxidant and cytotoxic activities
    Zamakshshari NH, Ee GCL, Ismail IS, Ibrahim Z, Mah SH
    Food Chem Toxicol, 2019 Nov;133:110800.
    PMID: 31479710 DOI: 10.1016/j.fct.2019.110800
    The stem bark of Calophyllum depressinervosum and Calophyllum buxifolium were extracted and examined for their antioxidant activities, together with cytotoxicity towards human cancer cells. The methanol extract of C. depressinervosum exhibited good DPPH and NO scavenging effects. The strongest BCB inhibition and FIC effects were shown by dichloromethane and ethyl acetate extracts of both species. Overall, DPPH, FRAP and FIC assays showed strong correlation with TPC. For cytotoxicity, hexane extract of C. depressinervosum possessed the strongest anti-proliferative activities towards SNU-1 cells while the hexane extract of C. buxifolium showed the strongest activity towards LS-174T and K562 cells with the IC50 values ranging from 7 to 17 μg/mL. The purification of plant extracts afforded eight xanthones, ananixanthone (1), caloxanthone B (2), caloxanthone I (3), caloxanthone J (4) xanthochymone B (5), thwaitesixanthone (6), 1,3,5,6-tetrahydroxyxanthone (7) and dombakinaxanthone (8). All the xanthones, except 1 were reported for the first time from both Calophyllum species. The xanthones were examined for their cytotoxic effect against K562 leukemic cells. Compounds 1 and 2 showed strong cytotoxicity with the IC50 values of 2.96 and 1.23 μg/mL, respectively. The molecular binding interaction of 2 was further investigated by performing molecular docking study with promising protein receptor Src kinase.
  12. Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities
    Wong KW, Teh SS, Law KP, Ismail IS, Sato K, Mase N, et al.
    Arch Pharm (Weinheim), 2023 Jan;356(1):e2200418.
    PMID: 36285691 DOI: 10.1002/ardp.202200418
    Oxidative stress and its constant companion, inflammation, play a critical part in the pathogenesis of many acute and chronic illnesses. The discovery of new multi-targeted drug candidates with antioxidant and anti-inflammatory properties is deemed necessary. Thus, a series of novel xanthone derivatives with halogenated benzyl (4b-4d, 4f-4h) and methoxylated benzyl groups (4e) attached to the butoxy amine substituent were synthesized in this study. The synthesized xanthone derivatives exhibited stronger antioxidant activity against H2 O2 scavenging than the standard drug, α-tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that, 4b-4d, 4f-4h demonstrated good anti-inflammatory activities through NO production inhibition towards lipopolysaccharide (LPS)-induced RAW 264.7 cells and showed 2-4 times stronger effects than the standard drug, diclofenac sodium. Moreover, compound 4b with two brominated benzyl groups attached to the butoxy amine substituent suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, significantly. Structure-activity relationship elucidated that the halogenated benzylamine substituent plays an important role in contributing the antioxidant and anti-inflammatory activities of xanthones. In summary, xanthone 4b was identified as a potential lead compound to be further developed into antioxidant and anti-inflammatory drugs. Thus, further studies on the related mechanisms of action of 4b are recommended.
  13. Comparative proteome analysis revealed potential biomarkers and the underlying immune mechanisms in Vibrio-resistant hybrid grouper, Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂
    Abu Aziz N, Christianus A, Wan Solahudin WMS, Ismail IS, Low CF
    J Fish Dis, 2024 Mar 24.
    PMID: 38523352 DOI: 10.1111/jfd.13940
    Vibrio alginolyticus is the causative agent of vibriosis, a common bacterial infection in grouper aquaculture that is associated with the development of haemorrhagic and non-haemorrhagic ulcerations on the fish. In the present study, comparative proteome analysis was performed on serum samples from Vibrio-resistant and Vibrio-susceptible grouper. Samples were analysed using high-throughput LC-MS/MS and identified 2770 unique peptides that corresponded to 344 proteins. Subsequent analysis identified 21 proteins that were significantly up-regulated in the resistant group compared to the control and the susceptible groups. Those proteins are associated with immunostimulatory effects, signalling and binding cascade, metabolism, and maintaining tissue integrity and physiological condition. Besides, potential protein biomarkers related to the immune system were identified, which could be associated with the disease-resistant phenotype. These data provide insights into the underlying immune mechanism of hybrid groupers upon Vibrio sp. infection.
  14. Fulltext Rapid Quantification and Validation of Biomarker Scopoletin in Paederia foetida by qNMR and UV-Vis for Herbal Preparation
    Tan DC, Quek A, Kassim NK, Ismail IS, Lee JJ
    Molecules, 2020 Nov 06;25(21).
    PMID: 33171900 DOI: 10.3390/molecules25215162
    Scopoletin has previously been reported as a biomarker for the standardization of Paederia foetida twigs. This study is the first report on the determination and quantification of scopoletin using quantitative nuclear magnetic resonance (qNMR) in the different extracts of Paederia foetida twigs. The validated qNMR method showed a good linearity (r2 = 0.9999), limit of detection (LOD) (0.009 mg/mL), and quantification (LOQ) (0.029 mg/mL), together with high stability (relative standard deviation (RSD) = 0.022%), high precision (RSD < 1%), and good recovery (94.08-108.45%). The quantification results of scopoletin concentration in chloroform extract using qNMR and microplate ultraviolet-visible (UV-vis) spectrophotometer was almost comparable. Therefore, the qNMR method is deemed accurate and reliable for quality control of Paederia foetida and other medicinal plants without extensive sample preparation.
  15. Fulltext NMR and LCMS analytical platforms exhibited the nephroprotective effect of Clinacanthus nutans in cisplatin-induced nephrotoxicity in the in vitro condition
    Mahmod II, Ismail IS, Alitheen NB, Normi YM, Abas F, Khatib A, et al.
    BMC Complement Med Ther, 2020 Oct 22;20(1):320.
    PMID: 33092571 DOI: 10.1186/s12906-020-03067-3
    BACKGROUND: Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities.

    METHODS: Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).

    RESULTS: NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.

    CONCLUSION: The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.

  16. Metabolic and biochemical changes in streptozotocin induced obese-diabetic rats treated with Phyllanthus niruri extract
    Mediani A, Abas F, Maulidiani M, Khatib A, Tan CP, Ismail IS, et al.
    J Pharm Biomed Anal, 2016 Sep 05;128:302-312.
    PMID: 27318080 DOI: 10.1016/j.jpba.2016.06.003
    Herbal medicine has been proven to be an effective therapy offering a variety of benefits, such as moderate reduction in hypoglycemia, in the treatment and prevention of obesity and diabetes. Phyllanthus niruri has been used as a treatment for diabetes mellitus. Herein, the induction of type 2 diabetes in Sprague-Dawley rats was achieved by a low dose of streptozotocin (STZ) (25mg/kgbw). Here, we evaluated the in vivo antidiabetic properties of two concentrations (250 and 500mg/kg bw) of P. niruri via metabolomics approach. The administration of 500mg/kgbw of P. niruri extract caused the metabolic disorders of obese diabetic rats to be improved towards the normal state. The extract also clearly decreased the serum glucose level and improved the lipid profile in obese diabetic rats. The results of this study may contribute towards better understanding the molecular mechanism of this medicinal plant in managing diabetes mellitus.
  17. Bioassay-guided identification of an anti-inflammatory prenylated acylphloroglucinol from Melicope ptelefolia and molecular insights into its interaction with 5-lipoxygenase
    Shaari K, Suppaiah V, Wai LK, Stanslas J, Tejo BA, Israf DA, et al.
    Bioorg Med Chem, 2011 Nov 1;19(21):6340-7.
    PMID: 21958738 DOI: 10.1016/j.bmc.2011.09.001
    A bioassay-guided investigation of Melicope ptelefolia Champ ex Benth (Rutaceae) resulted in the identification of an acyphloroglucinol, 2,4,6-trihydroxy-3-geranylacetophenone or tHGA, as the active principle inhibiting soybean 15-LOX. The anti-inflammatory action was also demonstrated on human leukocytes, where the compound showed prominent inhibitory activity against human PBML 5-LOX, with an IC(50) value of 0.42 μM, very close to the effect produced by the commonly used standard, NDGA. The compound concentration-dependently inhibited 5-LOX product synthesis, specifically inhibiting cysteinyl leukotriene LTC(4) with an IC(50) value of 1.80 μM, and showed no cell toxicity effects. The anti-inflammatory action does not seem to proceed via redox or metal chelating mechanism since the compound tested negative for these bioactivities. Further tests on cyclooxygenases indicated that the compound acts via a dual LOX/COX inhibitory mechanism, with greater selectivity for 5-LOX and COX-2 (IC(50) value of 0.40 μM). The molecular features that govern the 5-LOX inhibitory activity was thus explored using in silico docking experiments. The residues Ile 553 and Hie 252 were the most important residues in the interaction, each contributing significant energy values of -13.45 (electrostatic) and -5.40 kcal/mol (electrostatic and Van der Waals), respectively. The hydroxyl group of the phloroglucinol core of the compound forms a 2.56Å hydrogen bond with the side chain of the carboxylate group of Ile 553. Both Ile 553 and Hie 252 are crucial amino acid residues which chelate with the metal ion in the active site. Distorting the geometry of these ligands could be the reason for the inhibition activity shown by tHGA. The molecular simulation studies supported the bioassay results and served as a good model for understanding the way tHGA binds in the active site of human 5-LOX enzyme.
  18. Influence of Different Drying Treatments and Extraction Solvents on the Metabolite Profile and Nitric Oxide Inhibitory Activity of Ajwa Dates
    Abdul-Hamid NA, Abas F, Ismail IS, Shaari K, Lajis NH
    J Food Sci, 2015 Nov;80(11):H2603-11.
    PMID: 26457883 DOI: 10.1111/1750-3841.13084
    This study aimed to examine the variation in the metabolite profiles and nitric oxide (NO) inhibitory activity of Ajwa dates that were subjected to 2 drying treatments and different extraction solvents. (1)H NMR coupled with multivariate data analysis was employed. A Griess assay was used to determine the inhibition of the production of NO in RAW 264.7 cells treated with LPS and interferon-γ. The oven dried (OD) samples demonstrated the absence of asparagine and ascorbic acid as compared to the freeze dried (FD) dates. The principal component analysis showed distinct clusters between the OD and FD dates by the second principal component. In respect of extraction solvents, chloroform extracts can be distinguished by the absence of arginine, glycine and asparagine compared to the methanol and 50% methanol extracts. The chloroform extracts can be clearly distinguished from the methanol and 50% methanol extracts by first principal component. Meanwhile, the loading score plot of partial least squares analysis suggested that beta glucose, alpha glucose, choline, ascorbic acid and glycine were among the metabolites that were contributing to higher biological activity displayed by FD and methanol extracts of Ajwa. The results highlight an alternative method of metabolomics approach for determination of the metabolites that contribute to NO inhibitory activity.
  19. Relationship Between Metabolites Composition and Biological Activities of Phyllanthus niruri Extracts Prepared by Different Drying Methods and Solvents Extraction
    Mediani A, Abas F, Khatib A, Tan CP, Ismail IS, Shaari K, et al.
    Plant Foods Hum Nutr, 2015 Jun;70(2):184-92.
    PMID: 25800644 DOI: 10.1007/s11130-015-0478-5
    The study investigated the changes in the metabolite, antioxidant and α-glucosidase inhibitory activities of Phyllanthus niruri after three drying treatments: air, freeze and oven dryings. Water extracts and extracts obtained using different solvent ratios of ethanol and methanol (50, 70, 80 and 100%) were compared. The relationships among the antioxidant, α-glucosidase inhibitory activity and metabolite levels of the extracts were evaluated using partial least-square analysis (PLS). The solvent selectivity was assessed based on the phytochemical constituents present in the extract and their concentrations quantitatively analyzed using high performance liquid chromatography. The freeze-dried P. niruri samples that were extracted with the mixture of ethanol or methanol with low ratio of water showed higher biological activity values compared with the other extracts. The PLS results for the ethanolic with different ratio and water extracts demonstrated that phenolic acids (chlorogenic acid and ellagic acid) and flavonoids were highly linked to strong α-glucosidase inhibitory and antioxidant activities.
  20. Metabolomic analysis and biochemical changes in the urine and serum of streptozotocin-induced normal- and obese-diabetic rats
    Mediani A, Abas F, Maulidiani M, Abu Bakar Sajak A, Khatib A, Tan CP, et al.
    J Physiol Biochem, 2018 May 15.
    PMID: 29766441 DOI: 10.1007/s13105-018-0631-3
    Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated. The obese-diabetic model was developed by feeding the rats a high-fat diet and inducing diabetic conditions with a low dose of streptozotocin (STZ) (25 mg/kg bw). However, the normal rats were induced by a high dose of STZ (55 mg/kg bw). A partial least squares discriminant analysis (PLS-DA) model showed the biomarkers of both DM types compared to control. The synthesis and degradation of ketone bodies, tricarboxylic (TCA) cycles, and amino acid pathways were the ones most involved in the variation with the highest impact. The diabetic groups also exhibited a noticeable increase in the plasma glucose level and lipid profile disorders compared to the control. There was also an increase in the plasma cholesterol and low-density lipoprotein (LDL) levels and a decline in the high-density lipoprotein (HDL) of diabetic rats. The normal-diabetic rats exhibited the highest effect of all parameters compared to the obese-diabetic rats in the advancement of the DM period. This finding can build a platform to understand the metabolic and biochemical complications of both types of DM and can generate ideas for finding targeted drugs.
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