Displaying publications 1 - 20 of 79 in total

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  1. Nallappan D, Ong KC, Palanisamy UD, Chua KH, Kuppusamy UR
    Arch Physiol Biochem, 2023 Feb;129(1):186-197.
    PMID: 32813560 DOI: 10.1080/13813455.2020.1808019
    AIM: A high-fat diet (HFD) can lead to obesity and related metabolic disorders. This study evaluated the preventive efficacy of myricetin derivative-rich fraction (MD) from Syzygium malaccense leaf extract against HFD-induced obesity, hyperglycaemia, and oxidative stress in C57BL/6J mice.

    METHODS: HFD-fed mice were administered MD (50 mg/kg, 100 mg/kg, and 150 mg/kg) or 2 mg/kg metformin (positive control) orally for 16 weeks. Normal diet and HFD-fed control groups received normal saline.

    RESULTS: MD dose of 50 mg/kg was better than 100 mg/kg and 150 mg/kg in significantly reducing weight-gain, glucose intolerance, insulin resistance, lipid accumulation in liver and kidney, and improving the serum lipid profile. Lowered protein carbonyls and lipid hydroperoxides in urine and tissue homogenates and elevated reduced glutathione, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC) levels in tissue homogenates indicated amelioration of oxidative stress.

    CONCLUSION: MD has therapeutic value in the prevention and management of obesity, hyperglycaemia, and oxidative stress.

  2. Kanagasabapathy G, Kuppusamy UR, Abd Malek SN, Abdulla MA, Chua KH, Sabaratnam V
    PMID: 23259700 DOI: 10.1186/1472-6882-12-261
    BACKGROUND: Pleurotus sajor-caju (P. sajor-caju) has been extremely useful in the prevention of diabetes mellitus due to its low fat and high soluble fiber content for thousands of years. Insulin resistance is a key component in the development of diabetes mellitus which is caused by inflammation. In this study, we aimed to investigate the in vivo efficacy of glucan-rich polysaccharide of P. sajor-caju (GE) against diabetes mellitus and inflammation in C57BL/6J mice fed a high-fat diet.
    METHODS: Diabetes was induced in C57BL/6J mice by feeding a high-fat diet. The mice were randomly assigned to 7 groups (n=6 per group). The control groups in this study were ND (for normal diet) and HFD (for high-fat diet). The treated groups were ND240 (for normal diet) (240 mg/kg b.w) and HFD60, HFD120 and HFD240 (for high-fat), where the mice were administrated with three dosages of GE (60, 120, 240 mg GE/kg b.w respectively). Metformin (2 mg/kg b.w) served as positive control. The glucose tolerance test, glucose and insulin levels were measured at the end of 16 weeks. Expressions of genes for inflammatory markers, GLUT-4 and adiponectin in the adipose tissue of the mice were assessed. One-way ANOVA and Duncan's multiple range tests (DMRT) were used to determine the significant differences between groups.
    RESULTS: GE treated groups improved the glucose tolerance, attenuated hyperglycemia and hyperinsulinemia in the mice by up-regulating the adiponectin and GLUT-4 gene expressions. The mice in GE treated groups did not develop insulin resistance. GE also down-regulated the expression of inflammatory markers (IL-6, TNF-α, SAA2, CRP and MCP-1) via attenuation of nuclear transcription factors (NF-κB).
    CONCLUSION: Glucan-rich polysaccharide of P. sajor-caju can serve as a potential agent for prevention of glucose intolerance, insulin resistance and inflammation.
  3. Baskaran A, Chua KH, Sabaratnam V, Ravishankar Ram M, Kuppusamy UR
    BMC Complement Altern Med, 2017 Jan 13;17(1):40.
    PMID: 28086773 DOI: 10.1186/s12906-016-1546-6
    Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H2O2)-induced inflammation on RAW 264.7 macrophages was investigated.
  4. Azila N, Kuppusamy UR, Ong KK
    Biochem. Int., 1989 Nov;19(5):1077-85.
    PMID: 2561441
    Cyclic AMP phosphodiesterase (PDE) activity was assayed in the plasma membrane, mitochondrial and microsomal fractions of rat brain. The specific activity of the enzyme was highest in the plasma membrane fraction followed by mitochondrial and then the microsomal fraction. Phosphodiesterase activity of all three fractions was reduced after pretreatment with lecithinase C (PCase) from Clostridium perfringens but less markedly affected by the pretreatment with sphingomyelinase (SMase) from human placenta. The PDE activity of the plasma membrane fraction was more sensitive to PCase treatment compared with the other two particulate fractions, which showed only a slight loss of activity. Temperature seemed to affect PDE activity of the plasma membrane. The enzyme was quite stable at 30 degrees C but its activity dropped by approximately 46% at 37 degrees C after 90 min of incubation. Pretreatment of the plasma membrane at 30 degrees C with PCase at a concentration of more than 5 U caused a marked loss of PDE activity and the decrease in activity reached a plateau at concentrations above 10 U.
  5. Kuppusamy UR, Dharmani M, Kanthimathi MS, Indran M
    Biol Trace Elem Res, 2005 Jul;106(1):29-40.
    PMID: 16037608
    The trace elements copper, zinc, and selenium are important immune modulators and essential cofactors of the antioxidant enzymes. In the present study, the proliferative effect of human peripheral mononuclear cells (PBMCs) that have been exposed to copper, zinc, and selenium and the corresponding activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, were determined. Zinc and copper stimulated the PBMC proliferation in a dose-dependent manner within the dose range 25-200 micromol/L. SOD and GPx activities in PBMCs exposed to zinc were inhibited, whereas catalase activity was unaffected. All the three antioxidant enzymes in the cells exposed to copper were inhibited. Selenium exerted more potent inhibition of the cell proliferation while causing stimulation of the antioxidant enzymes at the lowest dose (25 micromol/L) than at the highest dose (200 micromol/L) tested. A significant negative correlation was observed between proliferation and antioxidant enzyme (SOD and GPx) activities in trace-element-exposed PBMC. The present findings substantiate the importance of trace elements as immune modulators and the involvement of enzymatic antioxidant system in the immune cell regulation.
  6. Lau MF, Chua KH, Sabaratnam V, Kuppusamy UR
    Biotechnol Appl Biochem, 2021 Aug;68(4):902-917.
    PMID: 32856730 DOI: 10.1002/bab.2013
    Ganoderma neo-japonicum is a well-known medicinal mushroom in Asian countries. However, scientific validations on its curative activities are confined to cirrhosis and diabetes. In this study, the anticancer properties of G. neo-japonicum were evaluated using cellular and computational models. The ethanolic extract (EtOH) with a promising inhibitory effect was fractionated into four different fractions: hexane (Hex), chloroform (Chl), butanol (Btn), and aqueous (Aq). The active fractions were then subjected to cell apoptosis assessment and phytochemical profiling. Molecular docking was conducted to elucidate the affinity of selected constituents towards antiapoptotic Bcl-2 protein. The butanol fraction showed the highest antioxidant activities as well as total phenolic content. Both hexane and chloroform fractions exerted a potent cytotoxic effect on colonic carcinoma cells through the induction of apoptosis. Phytochemical analysis revealed that the chloroform fraction is terpenoid enriched whereas the hexane fraction comprises predominantly sterol constituents. Stellasterol and 1,25-dihydroxyvitamin D3 3-glycoside were demonstrated to have a high affinity towards Bcl-2 protein. Overall, G. neo-japonicum can be considered as a compelling therapeutic candidate for cancer treatment.
  7. Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA
    Clin Chim Acta, 2005 Jan;351(1-2):197-201.
    PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014
    BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
    METHOD: The assays were carried out according to known established protocols.
    RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
    CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
  8. Wong FN, Tan JA, Keng TC, Ng KP, Chua KH, Kuppusamy UR
    Clin Chim Acta, 2016 Jan 30;453:56-61.
    PMID: 26657980 DOI: 10.1016/j.cca.2015.12.002
    BACKGROUND: This study aimed to investigate the relationship between soluble RAGE and estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD) after controlling for the potential confounding factors such as medication usage and enzymatic antioxidants.
    METHODS: A total of 222 CKD patients whose eGFR is less than 60ml/min/1.73m(2) and 111 non-CKD individuals were recruited. The study subjects were classified based on their diabetes status. The plasma glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities as well as plasma soluble RAGE level were measured.
    RESULTS: The plasma GPx and SOD activities were significantly lower and the plasma soluble RAGE level was significantly higher in the CKD patients than in the non-CKD individuals, regardless of the diabetes status. Soluble RAGE was significantly correlated with eGFR in both diabetic CKD (D-CKD) and non-diabetic CKD (ND-CKD) patients. The association between soluble RAGE and eGFR remained largely unaffected by the confounding factors in D-CKD patients. However, the confounding effect of enzymatic antioxidants in the relationship between eGFR and soluble RAGE was observed in ND-CKD patients.
    CONCLUSION: The increased plasma level of soluble RAGE is a better indicator of renal function decline in diabetic CKD patients instead of non-diabetic CKD patients.
    KEYWORDS: Chronic kidney disease; Diabetes; Enzymatic antioxidants; Glomerular filtration rate; Medications; Soluble RAGE
  9. Abd Rahim MR, Kho SL, Kuppusamy UR, Tan JA
    Clin. Lab., 2015;61(9):1325-30.
    PMID: 26554253
    BACKGROUND: Beta-thalassemia is the most common genetic disorder in Malaysia. Confirmation of the β-globin gene mutations involved in thalassemia is usually carried out by molecular analysis of DNA extracted from leukocytes in whole blood. Molecular analysis is generally carried out when affected children are around 1 - 2 years as clinical symptoms are expressed during this period. Blood taking at this age can be distressing for the child. High yield and pure DNA extracted from non-invasive sampling methods can serve as alternative samples in molecular studies for genetic diseases especially in pediatric cases.

    METHODS: In this study, mouthwash, saliva, and buccal cytobrush samples were collected from β-thalassemia major patients who had previously been characterized using DNA extracted from peripheral blood. DNA was extracted from mouthwash, saliva, and buccal cytobrush samples using the conventional inexpensive phenol-chloroform method and was measured by spectrophotometry for yield and purity. Molecular characterization of β-globin gene mutations was carried out using the amplification refractory mutation system (ARMS).

    RESULTS: DNA extracted from mouthwash, saliva, and buccal cytobrush samples produced high concentration and pure DNA. The purified DNA was successfully amplified using ARMS. Results of the β-globin gene mutations using DNA from the three non-invasive samples were in 100% concordance with results from DNA extracted from peripheral blood.

    CONCLUSIONS: The conventional in-house developed methods for non-invasive sample collection and DNA extraction from these samples are effective and negate the use of more expensive commercial kits. In conclusion, DNA extracted from mouthwash, saliva, and buccal cytobrush samples provided sufficiently high amounts of pure DNA suitable for molecular analysis of β-thalassemia.

  10. Ng ZX, Chua KH, Tajunisah I, Pendek R, Kuppusamy UR
    Clinics (Sao Paulo), 2013;68(2):185-93.
    PMID: 23525314 DOI: 10.6061/clinics/2013(02)oa11
    OBJECTIVE: This study aimed to assess the circulating levels of activated nuclear factor kappa B p65 and monocyte chemotactic protein-1 in diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs.

    METHODS: In total, 235 healthy controls and 371 Type 2 diabetic patients [171 without retinopathy (DNR) and 200 patients with retinopathy (diabetic retinopathy)] were recruited for this study. Plasma and the nuclear fraction of peripheral blood mononuclear cells were isolated for the quantification of the monocyte chemotactic protein-1 and nuclear factor kappa B p65 levels, respectively.

    RESULTS: Non-medicated diabetic retinopathy patients had significantly higher levels of activated nuclear factor kappa B p65 and plasma monocyte chemotactic protein-1 than DNR patients. Diabetic retinopathy patients who were taking antihyperglycemic and antihypertensive drugs showed significant reductions in both the nuclear factor kappa B p65 and monocyte chemotactic protein-1 levels compared with the non-medicated patients.

    CONCLUSION: This study demonstrated the significant attenuation of both the nuclear factor kappa B p65 and circulating monocyte chemotactic protein-1 levels in diabetic retinopathy patients taking antihyperglycemic and antihypertensive drugs.
  11. Lee VS, Sukumaran SD, Tan PK, Kuppusamy UR, Arumugam B
    Comput Biol Chem, 2021 Jun;92:107501.
    PMID: 33989998 DOI: 10.1016/j.compbiolchem.2021.107501
    Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH2) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH3+). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.
  12. Ng ZX, Kuppusamy UR, Tajunisah I, Fong KC, Chua KH
    Diabetes Res Clin Pract, 2012 Mar;95(3):372-7.
    PMID: 22154374 DOI: 10.1016/j.diabres.2011.11.005
    Conflicting results have been reported in different populations on the association between two particular RAGE gene polymorphisms (-429T/C and -374T/A) and retinopathy in diabetic patients. Therefore this study was designed to assess the association between both gene polymorphisms with retinopathy in Malaysian diabetic patients. A total of 342 type 2 diabetic patients [171 without retinopathy (DNR) and 171 with retinopathy (DR)] and 235 healthy controls were included in this study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism approach. Overall, the genotype distribution for both polymorphisms was not statistically different (p>0.05) among the control, DNR and DR groups. The -429C minor allele frequency of DR group (12.0%) was not significantly different (p>0.05) when compared to DNR group (16.1%) and healthy controls (11.3%). The -374A allele frequency also did not differ significantly between the control and DNR (p>0.05), control and DR (p>0.05) as well as DNR and DR groups (p>0.05). This is the first study report on RAGE gene polymorphism in Malaysian DR patients. In conclusion, -429T/C and -374T/A polymorphisms in the promoter region of RAGE gene were not associated with Malaysian type 2 DR patients.
  13. Kuppusamy UR, Indran M, Rokiah P
    Diabet Med, 2005 Oct;22(10):1343-6.
    PMID: 16176194 DOI: 10.1111/j.1464-5491.2005.01630.x
    Aims: Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant-antioxidant levels in these patients.

    Methods: Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods.

    Results: Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA(1c), fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant-antioxidant parameters as a function of HbA(1c) in each ethnic group revealed a strong association of HbA(1c) with oxidative indices.

    Conclusions: The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA(1c) remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration.
  14. Mhd Omar NA, Abdullah S, Abdullah N, Kuppusamy UR, Abdulla MA, Sabaratnam V
    Drug Des Devel Ther, 2015;9:5957-64.
    PMID: 26604694 DOI: 10.2147/DDDT.S90746
    Lentinus squarrosulus is an edible wild mushroom commonly found in Asia. This species has several interesting features such as rapid mycelial growth, and hence has the potential to be used as food, functional food, and nutraceuticals. Our previous study shows that L. squarrosulus contains potent antioxidant compounds in vitro. This study aims to investigate the in vivo bioavailability of L. squarrosulus mycelium extract and its antioxidant effect on biomarkers of antioxidant defense and oxidative stress.
  15. Lau MF, Vellasamy S, Chua KH, Sabaratnam V, Kuppusamy UR
    EXCLI J, 2018;17:186-199.
    PMID: 29743857 DOI: 10.17179/excli2018-1011
    Colorectal cancer (CRC) is the third most leading cause of morbidity and mortality throughout the world. 5-fluorouracil (5-FU), which is often administrated to disrupt carcinogenesis, was found to elevate blood glucose level among CRC patients. Thus, this study was conducted to evaluate the influence of rosiglitazone on antiproliferative effect of 5-FU using cellular model. Two human colonic carcinoma cell lines (HCT 116 and HT 29) were cultured in the presence of 5-FU, rosiglitazone or in combination under normal and high glucose concentration. The drug cytotoxicity was evaluated using the MTT assay whereas the assessment of cell cycle was carried out using the flow cytometry technique. Combination index (CI) method was used to determine the drug interaction between rosiglitazone and 5-FU. High glucose diminished the cytotoxic effect of 5-FU but at a high drug dosage, this effect could be overcome. Cell cycle analysis demonstrated that 5-FU and rosiglitazone caused G1-phase arrest and S-phase arrest, respectively. CI values indicated that rosiglitazone exerted synergistic effect on 5-FU regardless of glucose levels. This study is the first to demonstrate the influence of rosiglitazone on cytotoxicity of 5-FU under normal or high glucose level. Rosiglitazone may be a promising drug for enhancing the efficacy of 5-FU in the treatment of CRC associated with hyperglycemia.
  16. Jinam TA, Phipps ME, Indran M, Kuppusamy UR, Mahmood AA, Hong LC, et al.
    Ethn Health, 2008 Jun;13(3):277-87.
    PMID: 18568977 DOI: 10.1080/13557850801930478
    Health scenarios are constantly evolving, particularly in developing countries but little is known regarding the health status of indigenous groups in Malaysia. This study aims to elucidate the current health status in four indigenous populations in the country, who by and large been left out of mainstream healthcare developments.
  17. Wong KH, Naidu M, David P, Abdulla MA, Abdullah N, Kuppusamy UR, et al.
    PMID: 21941586 DOI: 10.1093/ecam/neq062
    Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.
  18. Mhd Omar NA, Abdullah N, Kuppusamy UR, Abdulla MA, Sabaratnam V
    PMID: 21423634 DOI: 10.1155/2011/539356
    Water extract of Lentinus squarrosulus mycelia was analysed for nutritional content, antioxidant capacity, and antiulcer ability. The extract contains high protein (57.6 g/100 g) and low total fat (0.5 g/100 g) and is rich in magnesium (0.4 g/100 g), potassium (3.8 g/100 g), vitamins B(1) (1.42 mg/100 g), and B(3) (194.29 mg/100 g) with total phenolic content of 39.16 mg/100 g. The cupric reducing antioxidant capacity and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of the extract were A(450) of 0.20 ± 0.03 at 0.5 mg/ml and IC(50) of 14.29 mg/ml, respectively. Oral feeding of L. squarrosulus extract (250 mg/kg) offered significant gastric mucosal protection of Sprague-Dawley rats compared to cimetidine (50 mg/kg). The ulcer healing rate of ulcerated rats after 24, 48, and 72 hours of treatment was 82%, 90%, and 100%, respectively. The IL-1β level in the serum and the NF-κB level in the tissues indicate that the healing potential was associated with attenuation of proinflammatory cytokines.
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