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  1. Syarifah-Noratiqah, S.B., Zulfarina, M.S., 'Atiqah, A., Qodriyah, H.M.S., Naina-Mohamed, I., Fairus, S.
    Medicine & Health, 2018;13(1):29-48.
    MyJurnal
    Hyperlipidemia is a condition of high lipid levels in the plasma and often linked with the deposition of lipid droplets in the aorta which initiate the progression of atherosclerosis. Atherosclerosis is a common cardiovascular disorder initiated by the formation of foams cells in the vascular wall which leads to turbulent blood flow, injury to the endothelial layer and subsequent vascular thrombosis. Since the early 1980’s, Golden-Syrian hamsters have been widely used as an animal model in the research of hyperlipidemia and atherosclerosis. The use of hamsters in the hyperlipidemic and atherosclerotic model is due to their lipoprotein profile that is closer to human setting, sensitive to high-fat high-cholesterol (HFHC) diet and a suitable rodent model. Atherosclerosis can be induced in hamsters through dietary challenge with HFHC diet. Over the decades, coconut oil (CNO) was commonly used as the source of fat in the diet design of high saturated fatty acids (SFA) composition. In this review, we summarized published literature with designs involving CNO plus cholesterol-induced hyperlipidemia, atherosclerosis or both. The factors that may influence the ability of CNO and cholesterol combination to induce hyperlipidemia such as the period of dietary intervention, hamster strains and the dietary amount were evaluated and summarized.
  2. Ibrahim N', Fairus S, Mohamed IN
    Nutrients, 2020 Jul 10;12(7).
    PMID: 32664390 DOI: 10.3390/nu12072055
    Cardiovascular disease (CVD) is globally known as the number one cause of death with hyperlipidemia as a strong risk factor for CVD. The initiation of drug treatment will be recommended if lifestyle modification fails. However, medicines currently used for improving cholesterol and low-density lipoprotein cholesterols (LDL-C) levels have been associated with various side effects. Thus, alternative treatment with fewer or no side effects needs to be explored. A potential agent, oil palm phenolics (OPP) recovered from the aqueous waste of oil palm milling process contains numerous water-soluble phenolic compounds. It has been postulated that OPP has shown cardioprotective effects via several mechanisms such as cholesterol biosynthesis pathway, antioxidant and anti-inflammatory properties. This review aims to summarize the current evidence explicating the actions of OPP in cardiovascular health and the mechanisms that maybe involved for the cardioprotective effects.
  3. Fairus S, Cheng HM, Sundram K
    J Integr Med, 2020 Jan;18(1):68-79.
    PMID: 31812339 DOI: 10.1016/j.joim.2019.11.005
    OBJECTIVE: Tocotrienols (T3s) have been hypothesized to have greater antioxidant capacity than tocopherols (Ts) due to differences in biokinetics that affect their absorption and function. The present trial compares the antioxidant effectiveness following postprandial challenge of two different doses of α-T or palm T3-rich fraction (TRF) treatments and evaluates their dose-response effects on antioxidant status.

    METHODS: Ten healthy volunteers were given four different doses of vitamin E formulations (268 mg α-T, 537 mg α-T, 263 mg TRF or 526 mg TRF) in a cross-over postprandial trial. Blood was sampled at 0, 2, 4, 5, 6 and 8 hours after meal consumption and plasma antioxidant status including total glutathione, superoxide dismutase, malondialdehyde (MDA), ferric reducing antioxidant potential and trolox-equivalent antioxidant capacity, was analyzed.

    RESULTS: Supplementation with the different doses of either α-T or TRF did not significantly improve overall antioxidant status. There was no significant difference in overall antioxidant status among treatments at the different doses compared. However, a significant dose-response effect was observed for plasma MDA throughout the 8-hour postprandial period. MDA was significantly lower after the 537 mg α-T treatment, compared to the 268 mg α-T treatment; it was also lower after the 526 mg TRF treatment compared to the 263 mg TRF treatment (P 

  4. Leow SS, Fairus S, Sambanthamurthi R
    Crit Rev Food Sci Nutr, 2022;62(32):9076-9092.
    PMID: 34156318 DOI: 10.1080/10408398.2021.1939648
    The oil palm (Elaeis guineensis) fruit is a source of vegetable oil and various phytonutrients. Phytochemical compounds present in palm oil include tocotrienols, carotenoids, phytosterols, squalene, coenzyme Q10, and phospholipids. Being a fruit, the oil palm is also a rich source of water-soluble phytonutrients, including phenolic compounds. Extraction of phytonutrients from the oil palm vegetation liquor of palm oil milling results in a phenolic acid-rich fraction termed Water-Soluble Palm Fruit Extract (WSPFE). Pre-clinical in vitro, ex vivo, and in vivo studies carried out using various biological models have shown that WSPFE has beneficial bioactive properties, while clinical studies in healthy volunteers showed that it is safe for human consumption and confers antioxidant and anti-inflammatory effects. The composition, biological properties, and relevant molecular mechanisms of WSPFE discovered thus far are discussed in the present review, with a view to offer future research perspectives on WSPFE for health and non-health applications.
  5. Fairus S, Nor RM, Cheng HM, Sundram K
    Nutr J, 2012;11:5.
    PMID: 22252050 DOI: 10.1186/1475-2891-11-5
    Tocotrienols (T3) and tocopherols (T), both members of the natural vitamin E family have unique biological functions in humans. T3 are detected in circulating human plasma and lipoproteins, although at concentrations significantly lower than α-tocopherol (α-T). T3, especially α-T3 is known to be neuropotective at nanomolar concentrations and this study evaluated the postprandial fate of T3 and α-T in plasma and lipoproteins.
  6. Ibrahim N', Fairus S, Zulfarina MS, Naina Mohamed I
    Nutrients, 2020 Feb 05;12(2).
    PMID: 32033387 DOI: 10.3390/nu12020414
    INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death worldwide. Squalene (SQ), an intermediate for the cholesterol biosynthesis, has been proposed to act similarly to statins via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the liver.

    PURPOSE: This paper explores the effects of SQ in CVD.

    METHODS: A systematic review of the literature was performed to identify relevant studies about SQ and CVD. A comprehensive search in Medline and Scopus for relevant studies published between the years 1946 and 2019 was performed. The main inclusion criteria were that the study was published in English; that the study reported association or effect of SQ and CVD; and that CVD should be related to lifestyle variables, aging, or experimentally induced conditions.

    RESULTS: The literature searches identified 5562 potentially relevant articles, whereby 21 studies met the inclusion criteria. There were three human studies and 18 animal experimental studies included in this paper. Only one human study reported positive outcome of SQ in CVD. The remaining two studies reported inconsistent and/or no effect. For animal studies, 15 studies reported positive effect while the remaining reported negative and/or no effect of SQ on various related parameters.

    CONCLUSIONS: This evidence-based review emphasizes the potential of SQ being used for cardiovascular-related diseases. The effect of SQ, especially of plant-based warrants further exploration. Controlled human observational studies should be performed to provide comprehensive evidence.

  7. Fairus S, Nor RM, Cheng HM, Sundram K
    Am J Clin Nutr, 2006 Oct;84(4):835-42.
    PMID: 17023711
    BACKGROUND: The detection of tocotrienols in human plasma has proven elusive, and it is hypothesized that they are rapidly assimilated and redistributed in various mammalian tissues.

    OBJECTIVE: The primary study objective was to evaluate the postprandial fate of tocotrienols and alpha-tocopherol in human plasma and lipoproteins.

    DESIGN: Seven healthy volunteers (4 males, 3 females) were administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of tocopherol and tocotrienol isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were measured at each interval.

    RESULTS: After intervention with TRF, plasma tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than alpha-tocopherol concentrations. In comparison, plasma alpha-tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the alpha-tocopherol treatments.

    CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is alpha-tocopherol. This finding confirms previous observations that, in the fasted state, tocotrienols are not detected in plasma. Tocotrienol transport in lipoproteins appears to follow complex biochemically mediated pathways within the lipoprotein cascade.

  8. Syarifah-Noratiqah SB, Zulfarina MS, Ahmad SU, Fairus S, Naina-Mohamed I
    Int J Med Sci, 2019;16(5):711-719.
    PMID: 31217739 DOI: 10.7150/ijms.29934
    The oil palm tree (Elaeis guineensis) from the family Arecaceae is a high oil-producing agricultural crop. A significant amount of vegetation liquor is discarded during the palm oil milling process amounting to 90 million tons per year around the world. This water-soluble extract is rich in phenolic compounds known as Oil Palm Phenolics (OPP). Several phenolic acids including the three isomers of caffeoylshikimic acid (CFA), p-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA) and hydroxytyrosol are among the primary active ingredients in the OPP. Previous investigations have reported several positive pharmacological potentials by OPP such as neuroprotective and atheroprotective effects, anti-tumor and reduction in Aβ deposition in Alzheimer's disease model. In the current review, the pharmacological potential for CFA, PHBA, PCA and hydroxytyrosol is carefully reviewed and evaluated.
  9. Syarifah-Noratiqah SB, Fairus S, Zulfarina MS, Nasrullah Z, Qodriyah HMS, Naina-Mohamed I
    Front Vet Sci, 2020;7:303.
    PMID: 32775343 DOI: 10.3389/fvets.2020.00303
    Background: Accumulative evidences on the beneficial effects of palm oil are progressively reported; however, there are still several controversies related to their effects on the risks of cardiovascular disease (CVD). This review explores the effects of palm oil and its liquid fraction namely palm olein, which is commonly used as cooking oil on four lipid parameters; total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), which play an important role as CVD-related biomarkers. A systematic review of the literature was conducted to identify the relevant studies on palm oil and the lipid parameters specifically focusing on the in-vivo animal model. Methods: A comprehensive search was conducted in Medline via EBSCOhost, Medline via OVID and Scopus. Studies were limited to the English language published between the years of 2000 and 2019. The main inclusion criteria were as follows: (1) Study with in-vivo animal experiments [the animal should be limited to mammals] (2) Study should have evaluated the effects of palm oil or palm olein on plasma or serum lipid parameter (3) Study should have used palm oil or palm olein in the form of pure or refined oil (4) The treatment of palm oil or palm olein was assessed using the following outcomes: plasma or serum TC, TG, HDL-C, and LDL-C concentration (5) Study should have control group and (6) studies on specific fatty acid, fraction enriched tocotrienol and tocopherol, crude palm oil, kernel oil, red palm oil, thermally oxidized palm oil, hydrogenated palm oil, and palm oil or palm olein based products namely margarine, palm milk, butter and cream were excluded. The quality and the risk of bias on the selected studies were assessed using the ARRIVE Guideline and SYRCLE's Risk of Bias tools, respectively. Results: The literature search successfully identified 17 potentially relevant articles, whereby nine of them met the inclusion criteria. All research articles included in this review were in vivo studies comprising seven rats, one hamster and one mice model. Conclusion: Significant positive outcomes were observed in several lipid parameters such as TC and LDL-C. The evidence from this review supported that palm oil and palm olein possess high potential as lipid-lowering agents.
  10. Fairus S, Leow SS, Mohamed IN, Tan YA, Sundram K, Sambanthamurthi R
    Sci Rep, 2018 05 29;8(1):8217.
    PMID: 29844318 DOI: 10.1038/s41598-018-26384-7
    Plant phenolics are being increasingly consumed globally with limited scientific and clinical evidence pertaining to safety and efficacy. The oil palm fruit contains a cocktail of phenolics, and palm oil production results in high volumes of aqueous by-products enriched in phenolics and bioactives. Several lines of evidence from in vitro and in vivo animal studies confirmed that the aqueous extract enriched in phenolics and other bioactives collectively known as oil palm phenolics (OPP) is safe and has potent bioactivity. A phase one clinical trial was conducted to evaluate the safety and effects of OPP in healthy volunteers. In this single-blind trial, 25 healthy human volunteers were supplemented with 450 mg gallic acid equivalent (GAE)/day of OPP or control treatments for a 60-day period. Fasting blood and urine samples were collected at days 1, 30 and 60. Medical examination was performed during these trial interventions. All clinical biochemistry profiles observed throughout the control and OPP treatment period were in the normal range with no major adverse effect (AE) or serious adverse effect (SAE) observed. Additionally, OPP supplementation resulted in improvement of total cholesterol and LDL-C levels, compared to the control treatment. The outcomes support our previous observations that OPP is safe and may have a protective role in reducing cholesterol levels.
  11. Leow SS, Khoo JS, Lee WK, Hoh CC, Fairus S, Sambanthamurthi R, et al.
    J Appl Genet, 2024 Dec;65(4):867-895.
    PMID: 38890243 DOI: 10.1007/s13353-024-00880-1
    Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both deterred diabetes onset in NRs fed a high-carbohydrate (hiCHO) diet, but the liquid form provided better protection. In this study, NRs were fed either a hiCHO diet or the same diet added with liquid or powder WSPFE. Following feeding of the diets for 8 weeks, random blood glucose levels were measured to categorize NRs as either diabetes-resistant or diabetes-susceptible, based on a cut-off value of 75 mg/dL. Livers were then obtained for Illumina HiSeq 4000 paired end RNA-sequencing (RNA-Seq) and the data were mapped to the reference genome. Consistent with physiological and biochemical parameters, the gene expression data obtained indicated that WSPFE was associated with protection against diabetes. Among hepatic genes upregulated by WSPFE versus controls, were genes related to insulin-like growth factor binding protein, leptin receptor, and processes of hepatic metabolism maintenance, while those downregulated were related to antigen binding, immunoglobulin receptor, inflammation- and cancer-related processes. WSPFE supplementation thus helped inhibit diabetes progression in NRs by increasing insulin sensitivity and reducing both the inflammatory effects of a hiCHO diet and the related DNA-damage compensatory mechanisms contributing to liver disease progression. In addition, the genetic permissiveness of susceptible NRs to develop diabetes was potentially associated with dysregulated compensatory mechanisms involving insulin signaling and oxidative stress over time. Further studies on other NR organs associated with diabetes and its complications are warranted.
  12. Leow SS, Lee WK, Khoo JS, Teoh S, Hoh CC, Fairus S, et al.
    Mol Biol Rep, 2020 Dec;47(12):9409-9427.
    PMID: 33222119 DOI: 10.1007/s11033-020-06003-3
    The Nile rat (Arvicanthis niloticus) is a novel diurnal carbohydrate-sensitive rodent useful for studies on type 2 diabetes mellitus (T2DM) and the metabolic syndrome. Hepatic responses to T2DM and any interventions thereof can be evaluated via transcriptomic gene expression analysis. However, the study of gene expression via real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) requires identification of stably expressed reference genes for accurate normalisation. This study describes the evaluation and identification of stable reference genes in the livers from Control Nile rats as well as those supplemented with Water-Soluble Palm Fruit Extract, which has been previously shown to attenuate T2DM in this animal model. Seven genes identified as having stable expression in RNA-Sequencing transcriptome analysis were chosen for verification using real-time RT-qPCR. Six commonly used reference genes from previous literature and two genes from a previous microarray gene expression study in Nile rats were also evaluated. The expression data of these 15 candidate reference genes were analysed using the RefFinder software which incorporated analyses performed by various algorithms. The Hpd, Pnpla6 and Vpp2 genes were identified as the most stable across the 36 samples tested. Their applicability was demonstrated through the normalisation of the gene expression profiles of two target genes, Cela1 and Lepr. In conclusion, three novel reference genes which can be used for robust normalisation of real-time RT-qPCR data were identified, thereby facilitating future hepatic gene expression studies in the Nile rat.
  13. Sambanthamurthi R, Tan Y, Sundram K, Hayes KC, Abeywardena M, Leow SS, et al.
    Br J Nutr, 2011 Dec;106(11):1664-75.
    PMID: 21736778 DOI: 10.1017/S0007114511002133
    It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
  14. Weinberg RP, Koledova VV, Schneider K, Sambandan TG, Grayson A, Zeidman G, et al.
    Sci Rep, 2018 Nov 06;8(1):16423.
    PMID: 30401897 DOI: 10.1038/s41598-018-34763-3
    Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are becoming more prevalent and an increasing burden on society. Neurodegenerative diseases often arise in the milieu of neuro-inflammation of the brain. Reactive astrocytes are key regulators in the development of neuro-inflammation. This study describes the effects of Palm Fruit Bioactives (PFB) on the behavior of human astrocytes which have been activated by IL-1β. When activated, the astrocytes proliferate, release numerous cytokines/chemokines including TNFα, RANTES (CCL5), IP-10 (CXCL10), generate reactive oxygen species (ROS), and express specific cell surface biomarkers such as the Intercellular Adhesion Molecule (ICAM), Vascular Cellular Adhesion Molecule (VCAM) and the Neuronal Cellular Adhesion Molecule (NCAM). Interleukin 1-beta (IL-1β) causes activation of human astrocytes with marked upregulation of pro-inflammatory genes. We show significant inhibition of these pro-inflammatory processes when IL-1β-activated astrocytes are exposed to PFB. PFB causes a dose-dependent and time-dependent reduction in specific cytokines: TNFα, RANTES, and IP-10. We also show that PFB significantly reduces ROS production by IL-1β-activated astrocytes. Furthermore, PFB also reduces the expression of ICAM and VCAM, both in activated and naïve human astrocytes in vitro. Since reactive astrocytes play an essential role in the neuroinflammatory state preceding neurodegenerative diseases, this study suggests that PFB may have a potential role in their prevention and/or treatment.
  15. Muhammad Ismail Tadj NB, Ibrahim NI, Tg Abu Bakar Sidik TMI, Zulfarina MS, Haji Mohd Saad Q, Leow SS, et al.
    Front Pharmacol, 2023;14:1190663.
    PMID: 37484009 DOI: 10.3389/fphar.2023.1190663
    Introduction: Oil palm phenolic (OPP) is an antioxidant aqueous palm oil by-product and contains a high amount of phenolics. OPP has been proven to have many therapeutical benefits, and one of them is as an antihyperlipidemic agent. The previous phase 1 clinical trial proved OPP was safe to be orally consumed by healthy volunteers and yielded a good lipid profile. Thus, this phase 2 clinical trial was conducted to determine the effectiveness of OPP in improving the lipid profile among hyperlipidemic subjects. Methods: A parallel, placebo-controlled, randomized, double-blinded clinical trial was conducted for 2 months on 50 hyperlipidemic subjects aged 20-50 years old. The subjects were randomly distributed to two treatment arms with 25 participants each: control/placebo (11 males and 14 females) and 250 mg of OPP (10 males and 15 females). The subjects were required to consume one capsule per day for 60 days. Fasting blood sampling for routine blood profile (hematology, liver function, renal function, and lipid) analysis and a medical examination were conducted at baseline, day 30, and day 60. t-test analysis was used to compare the difference between two test groups. Results: The baseline lipid profile between control group (TC, 5.78 ± 0.52 mmol/L; LDL, 3.88 ± 0.51 mmol/L; HDL, 1.30 ± 0.25; TG, 1.30 ± 0.82), and 250 mg OPP (TC, 5.76 ± 0.54 mmol/L; LDL, 3.82 ± 0.59 mmol/L; HDL, 1.37 ± 0.34; TG, 1.25 ± 0.54) is insignificant. No serious adverse events (SAEs) were reported. No abnormality in fasting blood parameters in all groups was found. Compared to the control group among male participants, the 250 mg OPP group showed an improved serum triglyceride level. There were no statistically significant changes in all blood parameters from day 1 to day 60 with the exception of triglyceride level. Conclusion: The absence of SAEs reported and no abnormal findings in biochemistry and hematology results suggested that the 250 mg OPP was safe to be taken by hyperlipidemic patients with a high probability of reducing triglyceride level in hyperlipidemic male patients The outcomes from this phase II trial suggest that by incorporating OPP supplements into the diet may be a promising strategy for individuals with hyperlipidemia to improve their lipid profiles and reduce cardiovascular risk. However, more research is needed to fully understand the mechanisms of action and establish the long-term efficacy and safety of OPP supplementation in larger scale. Limitation: Small samples size hence lack of diversity (25 subjects per groups) and early sharing of treatment-response results. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04573218.
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