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Fulltext The molecular mechanism of the anticancer effect of Artonin E in MDA-MB 231 triple negative breast cancer cells

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.
Fulltext Phenolic Rich Extract from Clinacanthus nutans Attenuates Hyperlipidemia-Associated Oxidative Stress in Rats

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.
Fulltext Defatted Kenaf (Hibiscus cannabinus L.) Seed Meal and Its Phenolic-Saponin-Rich Extract Protect Hypercholesterolemic Rats against Oxidative Stress and Systemic Inflammation via Transcriptional Modulation of Hepatic Antioxidant Genes

Chan KW, Ismail M, Mohd Esa N, Mohamed Alitheen NB, Imam MU, Ooi J, et al.

Oxid Med Cell Longev, 2018;2018:6742571.
PMID: 29849908 DOI: 10.1155/2018/6742571

The present study aimed to investigate the antioxidant and anti-inflammatory properties of defatted kenaf seed meal (DKSM) and its phenolic-saponin-rich extract (PSRE) in hypercholesterolemic rats. Hypercholesterolemia was induced using atherogenic diet feeding, and dietary interventions were conducted by incorporating DKSM (15% and 30%) or PSRE (at 2.3% and 4.6%, resp., equivalent to the total content of DKSM-phenolics and saponins in the DKSM groups) into the atherogenic diets. After ten weeks of intervention, serum total antioxidant capacities of hypercholesterolemic rats were significantly enhanced by DKSM and PSRE supplementation (p < 0.05). Similarly, DKSM and PSRE supplementation upregulated the hepatic mRNA expression of antioxidant genes (Nrf2, Sod1, Sod2, Gsr, and Gpx1) of hypercholesterolemic rats (p < 0.05), except for Gpx1 in the DKSM groups. The levels of circulating oxidized LDL and proinflammatory biomarkers were also markedly suppressed by DKSM and PSRE supplementation (p < 0.05). In aggregate, DKSM and PSRE attenuated the hypercholesterolemia-associated oxidative stress and systemic inflammation in rats, potentially by enhancement of hepatic endogenous antioxidant defense via activation of the Nrf2-ARE pathway, which may be contributed by the rich content of phenolics and saponins in DKSM and PSRE. Hence, DKSM and PSRE are prospective functional food ingredients for the potential mitigation of atherogenic risks in hypercholesterolemic individuals.
Fulltext Edible Bird's Nest Prevents Menopause-Related Memory and Cognitive Decline in Rats via Increased Hippocampal Sirtuin-1 Expression

Hou Z, He P, Imam MU, Qi J, Tang S, Song C, et al.

Oxid Med Cell Longev, 2017;2017:7205082.
PMID: 29104731 DOI: 10.1155/2017/7205082

Menopause causes cognitive and memory dysfunction due to impaired neuronal plasticity in the hippocampus. Sirtuin-1 (SIRT1) downregulation in the hippocampus is implicated in the underlying molecular mechanism. Edible bird's nest (EBN) is traditionally used to improve general wellbeing, and in this study, we evaluated its effects on SIRT1 expression in the hippocampus and implications on ovariectomy-induced memory and cognitive decline in rats. Ovariectomized female Sprague-Dawley rats were fed with normal pellet alone or normal pellet + EBN (6, 3, or 1.5%), compared with estrogen therapy (0.2 mg/kg/day). After 12 weeks of intervention, Morris water maze (four-day trial and one probe trial) was conducted, and serum estrogen levels, toxicity markers (alanine transaminase, alkaline phosphatase, urea, and creatinine), and hippocampal SIRT1 immunohistochemistry were estimated after sacrifice. The results indicated that EBN and estrogen enhanced spatial learning and memory and increased serum estrogen and hippocampal SIRT1 expression. In addition, the EBN groups did not show as much toxicity to the liver as the estrogen group. The data suggested that EBN treatment for 12 weeks could improve cognition and memory in ovariectomized female rats and may be an effective alternative to estrogen therapy for menopause-induced aging-related memory loss.
Fulltext Effects of germinated brown rice and its bioactive compounds on the expression of the peroxisome proliferator-activated receptor gamma gene

Imam MU, Ismail M, Ithnin H, Tubesha Z, Omar AR

Nutrients, 2013 Feb;5(2):468-77.
PMID: 23389305 DOI: 10.3390/nu5020468

Dysregulated metabolism is implicated in obesity and other disease conditions like type 2 diabetes mellitus and cardiovascular diseases, which are linked to abnormalities of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been the focus of much research aimed at managing these diseases. Also, germinated brown rice (GBR) is known to possess antidiabetic, antiobesity and hypocholesterolemic effects. We hypothesized that GBR bioactive compounds may mediate some of the improvements in metabolic indices through PPARγ modulation. Cultured HEP-G2 cells were treated with 50 ppm and 100 ppm of extracts from GBR (GABA, ASG and oryzanol) after determination of cell viabilities using MTT assays. Results showed that all extracts upregulated the expression of the PPARγ. However, combination of all three extracts showed downregulation of the gene, suggesting that, in combination, the effects of these bioactives differ from their individual effects likely mediated through competitive inhibition of the gene. Upregulation of the gene may have therapeutic potential in diabetes mellitus and cardiovascular diseases, while its downregulation likely contributes to GBR's antiobesity effects. These potentials are worth studying further.
Fulltext Study on the potential toxicity of a thymoquinone-rich fraction nanoemulsion in Sprague Dawley rats

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.
Increased risk of insulin resistance in rat offsprings exposed prenatally to white rice

Imam MU, Ismail M, Ooi DJ, Sarega N, Ishaka A

Mol Nutr Food Res, 2015 Jan;59(1):180-4.
PMID: 25329877 DOI: 10.1002/mnfr.201400396

White rice (WR) is a major staple food for people in developing countries and it may be responsible for the growing incidence of type 2 diabetes. Nonpregnant Female Sprague Dawley rats fed with WR or brown rice (BR) for 8 weeks were mated with age-matched male rats maintained on normal pellet over the same period. Offsprings were fed normal pellet after weaning until 8 weeks postdelivery. Rats fed with WR and their offsprings showed worsened oral glucose tolerance test, lower serum adiponectin levels, and higher weights, homeostatic model assessment of insulin resistance, serum retinol binding protein-4 levels, and leptin levels, compared with the normal and BR groups, suggesting an increased risk of insulin resistance. Furthermore, transcriptional levels of genes involved in insulin signaling showed different expression patterns in the liver, muscle, and adipose tissues of mothers and offsprings in both WR and BR groups. The results propose that the cycle of WR-induced insulin resistance in offsprings due to prenatal exposure, followed by their consumption of WR later in life may contribute to diabetes incidents. These findings are worth studying further.
Nutrigenomic effects of germinated brown rice and its bioactives on hepatic gluconeogenic genes in type 2 diabetic rats and HEPG2 cells

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.
Fulltext A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women

Ibrahim RM, Hamdan NS, Mahmud R, Imam MU, Saini SM, Rashid SN, et al.

J Transl Med, 2014;12:82.
PMID: 24685020 DOI: 10.1186/1479-5876-12-82

The risk of cardiovascular diseases (CVD) is increased tremendously among menopausal women, and there is an increasing demand for alternative therapies for managing factors like dyslipidemia that contribute to CVD development.
Fulltext Nanoemulsification of Rice Bran Wax Policosanol Enhances Its Cardio-protective Effects via Modulation of Hepatic Peroxisome Proliferator-activated Receptor gamma in Hyperlipidemic Rats

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.
In utero Exposure to Germinated Brown Rice and Its GABA Extract Attenuates High-Fat-Diet-Induced Insulin Resistance in Rat Offspring

Adamu HA, Imam MU, Der-Jiun O, Ismail M

J Nutrigenet Nutrigenomics, 2017;10(1-2):19-31.
PMID: 28399529 DOI: 10.1159/000469663

BACKGROUND: Numerous studies have reported on the influence of diet on insulin resistance. Our study provides insight into the effect of germinated brown rice (GBR) and γ-aminobutyric acid (GABA) on early environment-driven programming and susceptibility to insulin resistance in rat offspring.
METHODS: Male rat offspring from female Sprague-Dawley rats fed with a high-fat diet (HFD) alone, HFD + GBR, or HFD + GABA extract throughout pregnancy and lactation were weaned 4 weeks after delivery and followed up for 8 weeks. A biochemical analysis and an assessment of the hepatic expression of insulin signaling genes were performed.
RESULTS: The results showed that intrauterine exposure to HFD caused metabolic perturbations in rat offspring which gravitated towards insulin resistance even though the rat offspring did not consume an HFD. GBR and GABA attenuated the HFD-induced changes by underlying regulation of the insulin signaling genes.
CONCLUSIONS: The results suggest that intake of GBR and GABA during pregnancy and lactation can influence the programming of genes in rat offspring, thereby enhancing insulin sensitivity.
Fulltext Curculigoside and polyphenol-rich ethyl acetate fraction of Molineria latifolia rhizome improved glucose uptake via potential mTOR/AKT activated GLUT4 translocation

Ooi J, Azmi NH, Imam MU, Alitheen NB, Ismail M

J Food Drug Anal, 2018 10;26(4):1253-1264.
PMID: 30249324 DOI: 10.1016/j.jfda.2018.03.003

Adipose tissue is one of the major organs responsible for rapid restoration of postprandial glucose fluxes. Being the major isoform of glucose transporter in adipose tissue, regulations of insulin-dependent GLUT4 trafficking have always been of research interest. The present study aimed to examine the molecular mechanisms underlying the efficacy of curculigoside and polyphenol-rich ethyl acetate fraction (EAF) of Molineria latifolia rhizome in triggering glucose uptake. We assessed the adipogenic potential and glucose uptake stimulatory activity of curculigoside and EAF by employing a murine 3T3-L1 adipocyte model. The transcriptional and translational expressions of selected intermediates in the insulin signalling pathway were evaluated. While curculigoside neither promoted adipogenesis nor activated peroxisome proliferator activated receptor gamma, treatment with polyphenol-rich EAF resulted otherwise. However, both treatments enhanced insulin-stimulated uptake of glucose. This was coupled with increased availability of GLUT4 at the plasma membrane of the differentiated adipocytes although the total GLUT4 protein level was unaffected. In addition, the treatment increased the phosphorylation of both AKT and mTOR, which have been reported to be associated with GLUT4 translocation. The present findings proposed that curculigoside and EAF increased glucose transport activity of 3T3-L1 adipocytes via GLUT4 translocation as a result of potential mTOR/AKT activation. The more potent efficacy observed with EAF suggested potential synergistic and multi-targeted action.
Clausenidin from Clausena excavata induces apoptosis in hepG2 cells via the mitochondrial pathway

Waziri PM, Abdullah R, Yeap SK, Omar AR, Abdul AB, Kassim NK, et al.

J Ethnopharmacol, 2016 Dec 24;194:549-558.
PMID: 27729282 DOI: 10.1016/j.jep.2016.10.030

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena excavata Burm.f. is used locally in folk medicine for the treatment of cancer in South East Asia.
AIM OF THE STUDY: To determine the mechanism of action of pure clausenidin crystals in the induction of hepatocellular carcinoma (hepG2) cells apoptosis.
MATERIALS AND METHODS: Pure clausenidin was isolated from Clausena excavata Burm.f. and characterized using (1)H and (13)C NMR spectra. Clausenidin-induced cytotoxicity was determined by MTT assay. The morphology of hepG2 after treatment with clausenidin was determined by fluorescence and Scanning Electron Microscopy. The effect of clausenidin on the apoptotic genes and proteins were determined by real-time qPCR and protein array profiling, respectively. The involvement of the mitochondria in clausenidin-induced apoptosis was investigated using MMP, caspase 3 and 9 assays.
RESULTS: Clausenidin induced significant (p<0.05) and dose-dependent apoptosis of hepG2 cells. Cell cycle assay showed that clausenidin induced a G2/M phase arrest, caused mitochondrial membrane depolarization and significantly (p<0.05) increased expression of caspases 3 and 9, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, clausenidin caused decreased expression of the anti-apoptotic protein, Bcl 2 and increased expression of the pro-apoptotic protein, Bax. This finding was confirmed by the downregulation of Bcl-2 gene and upregulation of the Bax gene in the treated hepG2 cells.
CONCLUSION: Clausenidin extracted from Clausena excavata Burm.f. is an anti-hepG2 cell compound as shown by its ability to induce apoptosis through the mitochondrial pathway of apoptosis. Clausenidin can potentially be developed into an anticancer compound.
Fulltext The hypocholesterolemic effect of germinated brown rice involves the upregulation of the apolipoprotein A1 and low-density lipoprotein receptor genes

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.
Fulltext Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats

Yida Z, Imam MU, Ismail M, Ooi DJ, Sarega N, Azmi NH, et al.

J Diabetes Res, 2015;2015:760535.
PMID: 26273674 DOI: 10.1155/2015/760535

Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance.
Fulltext High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats

Yida Z, Imam MU, Ismail M, Ismail N, Ideris A, Abdullah MA

J Biomed Sci, 2015;22:96.
PMID: 26498218 DOI: 10.1186/s12929-015-0211-6

Serum sialic acid levels are positively correlated with coronary artery disease and inflammation. Although sialic acid is a non-specific marker, it is considered sensitive likely due to its influence in sialylation of glycoprotein structures all over the body.
Iron-Binding Capacity of Defatted Rice Bran Hydrolysate and Bioavailability of Iron in Caco-2 Cells

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.
Fulltext Neuroprotective effects of germinated brown rice against hydrogen peroxide induced cell death in human SH-SY5Y cells

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.
Fulltext Effects of brown rice and white rice on expression of xenobiotic metabolism genes in type 2 diabetic rats

Imam MU, Ismail M

Int J Mol Sci, 2012;13(7):8597-608.
PMID: 22942722 DOI: 10.3390/ijms13078597

Xenobiotics constantly influence biological systems through several means of interaction. These interactions are disturbed in type 2 diabetes, with implications for disease outcome. We aimed to study the implications of such disturbances on type 2 diabetes and rice consumption, the results of which could affect management of the disease in developing countries. In a type 2 diabetic rat model induced through a combination of high fat diet and low dose streptozotocin injection, up-regulation of xenobiotic metabolism genes in the diabetic untreated group was observed. Xenobiotic metabolism genes were upregulated more in the white rice (WR) group than the diabetic untreated group while the brown rice (BR) group showed significantly lower expression values, though not as effective as metformin, which gave values closer to the normal non-diabetic group. The fold changes in expression in the WR group compared to the BR group for Cyp2D4, Cyp3A1, Cyp4A1, Cyp2B1, Cyp2E1, Cyp2C11, UGT2B1, ALDH1A1 and Cyp2C6 were 2.6, 2, 1.5, 4, 2.8, 1.5, 1.8, 3 and 5, respectively. Our results suggest that WR may upregulate these genes in type 2 diabetes more than BR, potentially causing faster drug metabolism, less drug efficacy and more toxicity. These results may have profound implications for rice eating populations, constituting half the world's population.
Fulltext Effects of white rice, brown rice and germinated brown rice on antioxidant status of type 2 diabetic rats

Imam MU, Musa SN, Azmi NH, Ismail M

Int J Mol Sci, 2012;13(10):12952-69.
PMID: 23202932 DOI: 10.3390/ijms131012952

Oxidative stress is implicated in the pathogenesis of diabetic complications, and can be increased by diet like white rice (WR). Though brown rice (BR) and germinated brown rice (GBR) have high antioxidant potentials as a result of their bioactive compounds, reports of their effects on oxidative stress-related conditions such as type 2 diabetes are lacking. We hypothesized therefore that if BR and GBR were to improve antioxidant status, they would be better for rice consuming populations instead of the commonly consumed WR that is known to promote oxidative stress. This will then provide further reasons why less consumption of WR should be encouraged. We studied the effects of GBR on antioxidant status in type 2 diabetic rats, induced using a high-fat diet and streptozotocin injection, and also evaluated the effects of WR, BR and GBR on catalase and superoxide dismutase genes. As dietary components, BR and GBR improved glycemia and kidney hydroxyl radical scavenging activities, and prevented the deterioration of total antioxidant status in type 2 diabetic rats. Similarly, GBR preserved liver enzymes, as well as serum creatinine. There seem to be evidence that upregulation of superoxide dismutase gene may likely be an underlying mechanism for antioxidant effects of BR and GBR. Our results provide insight into the effects of different rice types on antioxidant status in type 2 diabetes. The results also suggest that WR consumption, contrary to BR and GBR, may worsen antioxidant status that may lead to more damage by free radicals. From the data so far, the antioxidant effects of BR and GBR are worth studying further especially on a long term to determine their effects on development of oxidative stress-related problems, which WR consumption predisposes to.

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