Displaying publications 1 - 20 of 49 in total

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  1. Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, et al.
    Cell Mol Neurobiol, 2013 Nov;33(8):1159-69.
    PMID: 24101432 DOI: 10.1007/s10571-013-9982-z
    Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.
  2. Etti IC, Abdullah R, Kadir A, Hashim NM, Yeap SK, Imam MU, et al.
    PLoS One, 2017;12(8):e0182357.
    PMID: 28771532 DOI: 10.1371/journal.pone.0182357
    Nature has provided us with a wide spectrum of disease healing phytochemicals like Artonin E, obtained from the root bark of Artocarpus elasticus. This molecule had been predicted to be drug-like, possessing unique medicinal properties. Despite strides made in chemotherapy, prognosis of the heterogenous aggressive triple negative breast cancer is still poor. This study was conducted to investigate the mechanism of inhibition of Artonin E, a prenylated flavonoid on MDA-MB 231 triple negative breast cancer cell, with a view of mitigating the hallmarks displayed by these tumors. The anti-proliferative effect, mode of cell death and the mechanism of apoptosis induction were investigated. Artonin E, was seen to effectively relinquish MDA-MB 231 breast cancer cells of their apoptosis evading capacity, causing a half-maximal growth inhibition at low concentrations (14.3, 13.9 and 9.8 μM) after the tested time points (24, 48 and 72 hours), respectively. The mode of cell death was observed to be apoptosis with defined characteristics. Artonin E was seen to induce the activation of both extrinsic and intrinsic caspases initiators of apoptosis. It also enhanced the release of total reactive oxygen species which polarized the mitochondrial membrane, compounding the release of cytochrome c. Gene expression studies revealed the upregulation of TNF-related apoptosis inducing ligand and proapoptotic genes with down regulation of anti-apoptotic genes and proteins. A G2/M cell cycle arrest was also observed and was attributed to the observed upregulation of p21 independent of the p53 status. Interestingly, livin, a new member of the inhibitors of apoptosis was confirmed to be significantly repressed. In all, Artonin E showed the potential as a promising candidate to combat the aggressive triple negative breast cancer.
  3. Imam MU, Ismail M, Omar AR, Ithnin H
    J Diabetes Res, 2013;2013:134694.
    PMID: 23671850 DOI: 10.1155/2013/134694
    Germinated brown rice (GBR) is rich in bioactive compounds, which confer GBR with many functional properties. Evidence of its hypocholesterolemic effects is emerging, but the exact mechanisms of action and bioactive compounds involved have not been fully documented. Using type 2 diabetic rats, we studied the effects of white rice, GBR, and brown rice (BR) on lipid profile and on the regulation of selected genes involved in cholesterol metabolism. Our results showed that the upregulation of apolipoprotein A1 and low-density lipoprotein receptor genes was involved in the hypocholesterolemic effects of GBR. Additionally, in vitro studies using HEPG2 cells showed that acylated steryl glycoside, gamma amino butyric acid, and oryzanol and phenolic extracts of GBR contribute to the nutrigenomic regulation of these genes. Transcriptional and nontranscriptional mechanisms are likely involved in the overall hypocholesterolemic effects of GBR suggesting that it may have an impact on the prevention and/or management of hypercholesterolemia due to a wide variety of metabolic perturbations. However, there is need to conduct long-term clinical trials to determine the clinical relevance of the hypocholesterolemic effects of GBR determined through animal studies.
  4. Imam MU, Ismail M
    Glob Chall, 2017 Nov 16;1(8):1700043.
    PMID: 31565292 DOI: 10.1002/gch2.201700043
    Noncommunicable chronic diseases (NCCDs) are the leading causes of morbidity and mortality globally. The mismatch between present day diets and ancestral genome is suggested to contribute to the NCCDs burden, which is promoted by traditional risk factors like unhealthy diets, physical inactivity, alcohol and tobacco. However, epigenetic evidence now suggests that cumulatively inherited epigenetic modifications may have made humans more prone to the effects of present day lifestyle factors. Perinatal starvation was widespread in the 19th century. This together with more recent events like increasing consumption of western and low fiber diets, smoking, harmful use of alcohol, physical inactivity, and environmental pollutants may have programed the human epigenome for higher NCCDs risk. In this review, on the basis of available epigenetic data it is hypothesized that transgenerational effects of lifestyle factors may be contributing to the current global burden of NCCDs. Thus, there is a need to reconsider prevention strategies so that the subsequent generations will not have to pay for our sins and those of our ancestors.
  5. Tubesha Z, Imam MU, Mahmud R, Ismail M
    Molecules, 2013 Jun 26;18(7):7460-72.
    PMID: 23803717 DOI: 10.3390/molecules18077460
    Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.
  6. Ooi J, Adamu HA, Imam MU, Ithnin H, Ismail M
    Biomed Pharmacother, 2018 Feb;98:125-133.
    PMID: 29248832 DOI: 10.1016/j.biopha.2017.12.002
    This study aimed to evaluate the effect of ethyl acetate fraction (EAF) isolated from Molineria latifolia rhizome as dietary interventions for type 2 diabetes mellitus (T2DM) and its underlying molecular mechanisms in vivo. Experimental rats were induced by high fat diet feeding coupled with combined exposure to streptozotocin and nicotinamide. Treatment with EAF improved glucose tolerance and lipid profiles, but the insulin secretion was unaltered. Gene expression analyses on insulin/adipocytokine signalling-related genes demonstrated tissue-specific transcriptional responses. In skeletal muscle and liver tissues, Socs1, Tnf and Mapk8 showed consistent transcript regulation. Furthermore, hepatic translational analyses revealed sensitization on proximal insulin signalling, with reduced expression of IRS1 serine phosphorylation, increased IRS1 tyrosine phosphorylation and increased phospho-AKT (Ser473). The present findings suggested that EAF exerted its effect by modulating insulin signalling, potentially via IRS1/AKT activation. The pharmacological attributes of EAF may implicate its potential therapeutic applications for diabetes management.
  7. Sarega N, Imam MU, Ooi DJ, Chan KW, Md Esa N, Zawawi N, et al.
    Oxid Med Cell Longev, 2016;2016:4137908.
    PMID: 26881026 DOI: 10.1155/2016/4137908
    Clinacanthus nutans is used as traditional medicine in Asia but there are limited scientific studies to support its use. In this study, the stem and leaf of C. nutans were extracted using solvents of differing polarities, and their antioxidant capacities were determined using multiple antioxidant assays. The water and aqueous methanolic leaf extracts were further fractionated and their antioxidant capacities and phenolic compositions were tested. Furthermore, the efficacies of the water and aqueous methanolic leaf extracts were tested against hyperlipidemia-induced oxidative stress in rats. Serum and hepatic antioxidant and oxidative stress markers were tested after feeding the rats with high fat diet together with the extracts or simvastatin for 7 weeks. The results indicated that both leaf extracts attenuated oxidative stress through increasing serum antioxidant enzymes activity and upregulating the expression of hepatic antioxidant genes. Multiple phenolic compounds were detected in the extracts and fractions of C. nutans, although protocatechuic acid was one of the most abundant and may have contributed significantly towards the bioactivities of the extracts. However, synergistic effects of different phenolics may have contributed to the overall bioactivities. C. nutans can be a good source of functional ingredients for the management of oxidative stress-related diseases.
  8. Adamu HA, Imam MU, Ooi DJ, Esa NM, Rosli R, Ismail M
    Food Nutr Res, 2016;60:30209.
    PMID: 26842399 DOI: 10.3402/fnr.v60.30209
    Evidence suggests perinatal environments influence the risk of developing insulin resistance.
  9. Imam MU, Ismail M
    Mol Nutr Food Res, 2013 Mar;57(3):401-11.
    PMID: 23307605 DOI: 10.1002/mnfr.201200429
    SCOPE: Chronic sustained hyperglycemia underlies the symptomatology and complications of type 2 diabetes mellitus, and dietary components contribute to it. Germinated brown rice (GBR) improves glycemic control but the mechanisms involved are still the subject of debate. We now show one mechanism by which GBR lowers blood glucose.

    METHODS AND RESULTS: Effects of GBR, brown rice, and white rice (WR) on fasting plasma glucose and selected genes were studied in type 2 diabetic rats. GBR reduced plasma glucose and weight more than metformin, while WR worsened glycemia over 4 weeks of intervention. Through nutrigenomic suppression, GBR downregulated gluconeogenic genes (Fbp1 and Pck1) in a manner similar to, but more potently than, metformin, while WR upregulated the same genes. Bioactives (gamma-amino butyric acid, acylated steryl glycoside, oryzanol, and phenolics) were involved in GBR's downregulation of both genes. Plasma glucose, Fbp1 and Pck1 changes significantly affected the weight of rats (p = 0.0001).

    CONCLUSION: The fact that GBR downregulates gluconeogenic genes similar to metformin, but produces better glycemic control in type 2 diabetic rats, suggests other mechanisms are involved in GBR's antihyperglycemic properties. GBR as a staple could potentially provide enhanced glycemic control in type 2 diabetes mellitus better than metformin.

  10. Hou Z, Imam MU, Ismail M, Ooi DJ, Ideris A, Mahmud R
    Drug Des Devel Ther, 2015;9:4115-25.
    PMID: 26316695 DOI: 10.2147/DDDT.S80743
    Estrogen deficiency alters quality of life during menopause. Hormone replacement therapy has been used to improve quality of life and prevent complications, but side effects limit its use. In this study, we evaluated the use of edible bird's nest (EBN) for prevention of cardiometabolic problems in rats with ovariectomy-induced menopause. Ovariectomized female rats were fed for 12 weeks with normal rat chow, EBN, or estrogen and compared with normal non-ovariectomized rats. Metabolic indices (insulin, estrogen, superoxide dismutase, malondialdehyde, oral glucose tolerance test, and lipid profile) were measured at the end of the experiment from serum and liver tissue homogenate, and transcriptional levels of hepatic insulin signaling genes were measured. The results showed that ovariectomy worsened metabolic indices and disrupted the normal transcriptional pattern of hepatic insulin signaling genes. EBN improved the metabolic indices and also produced transcriptional changes in hepatic insulin signaling genes that tended toward enhanced insulin sensitivity, and glucose and lipid homeostasis, even better than estrogen. The data suggest that EBN could meliorate estrogen deficiency-associated increase in risk of cardiometabolic disease in rats, and may in fact be useful as a functional food for the prevention of such a problem in humans. The clinical validity of these findings is worth studying further.
  11. Ismail N, Ismail M, Fathy SF, Musa SN, Imam MU, Foo JB, et al.
    Int J Mol Sci, 2012;13(8):9692-708.
    PMID: 22949825 DOI: 10.3390/ijms13089692
    The neuroprotective and antioxidative effects of germinated brown rice (GBR), brown rice (BR) and commercially available γ-aminobutyric acid (GABA) against cell death induced by hydrogen peroxide (H(2)O(2)) in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H(2)O(2)-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.
  12. Abubakar MB, Usman D, El-Saber Batiha G, Cruz-Martins N, Malami I, Ibrahim KG, et al.
    Front Pharmacol, 2021;12:629935.
    PMID: 34012391 DOI: 10.3389/fphar.2021.629935
    The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.
  13. Ishaka A, Imam MU, Ismail M
    J Oleo Sci, 2020;69(10):1287-1295.
    PMID: 33028753 DOI: 10.5650/jos.ess20098
    Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.
  14. Yida Z, Imam MU, Ismail M, Wong W, Abdullah MA, Ideris A, et al.
    Food Nutr Res, 2015;59:29046.
    PMID: 26642300 DOI: 10.3402/fnr.v59.29046
    N-Acetylneuraminic acid (Neu5Ac), a type of sialic acid, has close links with cholesterol metabolism and is often used as a biomarker in evaluating the risk of cardiovascular diseases. However, most studies on the health implications of Neu5Ac have focused on its effects on the nervous system, while its effects on cardiovascular risk factors have largely been unreported. Thus, the effects of Neu5Ac on coagulation status in high fat diet (HFD)-induced hyperlipidemic rats were evaluated in this study.
  15. Yida Z, Imam MU, Ismail M, Ismail N, Azmi NH, Wong W, et al.
    Biomed Res Int, 2015;2015:602313.
    PMID: 26688813 DOI: 10.1155/2015/602313
    N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (P < 0.05). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further.
  16. Wong WT, Ismail M, Imam MU, Zhang YD
    BMC Complement Altern Med, 2016 Jul 28;16:252.
    PMID: 27465266 DOI: 10.1186/s12906-016-1223-9
    Rice bran is bioactive-rich and has proven health benefits for humans. Moreover, its source, the brown rice has antioxidant, hypolipidemic and other functional properties that are increasingly making it a nutritional staple especially in Asian countries. This study investigated the antiplatelet aggregation mechanisms of crude hexane/methanolic rice bran extract, in which policosanol was the targeted bioactive. Platelets play a vital role in pathogenesis of atherosclerosis and cardiovascular diseases, and their increased activities could potentially cause arterial thrombus formation or severe bleeding disorders. Thus, in this study, platelet aggregation and adhesion of platelets to major components of basal lamina were examined in vitro. In addition, cellular protein secretion was quantified as a measurement of platelet activation.
  17. Ismail N, Ismail M, Imam MU, Azmi NH, Fathy SF, Foo JB, et al.
    PMID: 25475556 DOI: 10.1186/1472-6882-14-467
    Apoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases.
  18. Hou Z, Imam MU, Ismail M, Azmi NH, Ismail N, Ideris A, et al.
    Biosci Biotechnol Biochem, 2015;79(10):1570-8.
    PMID: 26057702 DOI: 10.1080/09168451.2015.1050989
    There are reports of improved redox outcomes due to consumption of Edible Bird's Nest (EBN). Many of the functional effects of EBN can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of aging and its related diseases like Alzheimer's disease. In this study, the antioxidative potentials of EBN and its constituents, lactoferrin (LF) and ovotransferrin (OVF), were determined and protective effects against hydrogen peroxide (H2O2)- induced toxicity on SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange and propidium iodide (AO/PI) staining with microscopy were examined. Results showed that EBN and its constituents attenuated H2O2-induced cytotoxicity, and decreased radical oxygen species (ROS) through increased scavenging activity. Furthermore, LF, OVF, and EBN produced transcriptional changes in antioxidant related genes that tended towards neuroprotection as compared to H2O2-treated group. Overall, the results suggest that LF and OVF may produce synergistic or all-or-none antioxidative effects in EBN.
  19. Foong LC, Imam MU, Ismail M
    J Agric Food Chem, 2015 Oct 21;63(41):9029-36.
    PMID: 26435326 DOI: 10.1021/acs.jafc.5b03420
    The present study was aimed at utilizing defatted rice bran (DRB) protein as an iron-binding peptide to enhance iron uptake in humans. DRB samples were treated with Alcalase and Flavourzyme, and the total extractable peptides were determined. Furthermore, the iron-binding capacities of the DRB protein hydrolysates were determined, whereas iron bioavailability studies were conducted using an in vitro digestion and absorption model (Caco-2 cells). The results showed that the DRB protein hydrolysates produced by combined Alcalase and Flavourzyme hydrolysis had the best iron-binding capacity (83%) after 90 min of hydrolysis. The optimal hydrolysis time to produce the best iron-uptake in Caco-2 cells was found to be 180 min. The results suggested that DRB protein hydrolysates have potent iron-binding capacities and may enhance the bioavailability of iron, hence their suitability for use as iron-fortified supplements.
  20. Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, et al.
    PMID: 24947113 DOI: 10.1186/1472-6882-14-197
    Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
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