Displaying publications 81 - 100 of 102 in total

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  1. Makpol S, Zainuddin A, Chua KH, Yusof YA, Ngah WZ
    Clinics (Sao Paulo), 2012;67(2):135-43.
    PMID: 22358238
    OBJECTIVE: Human diploid fibroblasts undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular aging. The beneficial effects of vitamin E in aging have been established, but studies to determine the mechanisms of these effects are ongoing. This study determined the molecular mechanism of γ-tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human diploid fibroblasts using the expression of senescence-associated genes.

    METHODS: Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.

    RESULTS: The cell cycle was arrested in the G(0)/G(1) phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.

    CONCLUSION: γ-Tocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.

  2. Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA
    Nutr J, 2015;14:31.
    PMID: 25889965 DOI: 10.1186/s12937-015-0015-2
    The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.
  3. Wee LH, Morad NA, Aan GJ, Makpol S, Wan Ngah WZ, Mohd Yusof YA
    Asian Pac J Cancer Prev, 2015;16(15):6549-56.
    PMID: 26434873
    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.
  4. Hakim L, Alias E, Makpol S, Ngah WZ, Morad NA, Yusof YA
    Asian Pac J Cancer Prev, 2014;15(11):4651-7.
    PMID: 24969899
    The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75 mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75 mg/mL Gelam honey) synergistically lowered the IC50 of Gelam honey to 22 mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose- dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.
  5. Habib SH, Makpol S, Abdul Hamid NA, Das S, Ngah WZ, Yusof YA
    Clinics (Sao Paulo), 2008 Dec;63(6):807-13.
    PMID: 19061005
    OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFkappaB and TNF-alpha in liver cancer-induced rats.

    METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1% ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFkappaB and TNF-alpha.

    RESULTS: The expression of NFkappaB was detected in the choline-deficient diet group, with 88.3 +/- 1.83% of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFkappaB was significantly reduced, to 32.35 +/- 1.34% (p<0.05). In the choline-deficient diet group, 83.3 +/- 4.52% of samples showed positive staining of TNF-alpha, which was significantly reduced to 7.94 +/- 1.32% (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFkappaB and TNF-alpha in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group.

    CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFkappaB and TNF-alpha in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFkappaB through the suppression of the pro-inflammatory TNF-alpha.

  6. Saud Gany SL, Chin KY, Tan JK, Aminuddin A, Makpol S
    Front Pharmacol, 2023;14:1290721.
    PMID: 38146461 DOI: 10.3389/fphar.2023.1290721
    Musculoskeletal health is paramount in an ageing population susceptible to conditions such as osteoporosis, arthritis and fractures. Age-related changes in bone, muscle, and joint function result in declining musculoskeletal health, reduced mobility, increased risk of falls, and persistent discomfort. Preserving musculoskeletal wellbeing is essential for maintaining independence and enhancing the overall quality of life for the elderly. The global burden of musculoskeletal disorders is significant, impacting 1.71 billion individuals worldwide, with age-related muscle atrophy being a well-established phenomenon. Tocotrienols, a unique type of vitamin E found in various sources, demonstrate exceptional antioxidant capabilities compared to tocopherols. This characteristic positions them as promising candidates for addressing musculoskeletal challenges, particularly in mitigating inflammation and oxidative stress underlying musculoskeletal disorders. This review paper comprehensively examines existing research into the preventive and therapeutic potential of tocotrienols in addressing age-related musculoskeletal issues. It sheds light on the promising role of tocotrienols in enhancing musculoskeletal health and overall wellbeing, emphasizing their significance within the broader context of age-related health concerns.
  7. Mohd Sahardi NFN, Jaafar F, Tan JK, Mad Nordin MF, Makpol S
    Nutrients, 2023 Oct 25;15(21).
    PMID: 37960173 DOI: 10.3390/nu15214520
    (1) Background: Muscle loss is associated with frailty and a reduction in physical strength and performance, which is caused by increased oxidative stress. Ginger (Zingiber officinale Roscoe) is a potential herb that can be used to reduce the level of oxidative stress. This study aimed to determine the effect of ginger on the expression of metabolites and their metabolic pathways in the myoblast cells to elucidate the mechanism involved and its pharmacological properties in promoting myoblast differentiation. (2) Methods: The myoblast cells were cultured into three stages (young, pre-senescent and senescent). At each stage, the myoblasts were treated with different concentrations of ginger extract. Then, metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry (LCMS/MS). (3) Results: Nine metabolites were decreased in both the pre-senescent and senescent control groups as compared to the young control group. For the young ginger-treated group, 8-shogaol and valine were upregulated, whereas adipic acid and bis (4-ethyl benzylidene) sorbitol were decreased. In the pre-senescent ginger-treated group, the niacinamide was upregulated, while carnitine and creatine were downregulated. Ginger treatment in the senescent group caused a significant upregulation in 8-shogaol, octadecanamide and uracil. (4) Conclusions: Ginger extract has the potential as a pharmacological agent to reduce muscle loss in skeletal muscle by triggering changes in some metabolites and their pathways that could promote muscle regeneration in ageing.
  8. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Makpol S, et al.
    J Alzheimers Dis, 2019;72(1):229-246.
    PMID: 31594216 DOI: 10.3233/JAD-181171
    Tocotrienol-rich fraction (TRF) is a mixture of vitamin E analogs derived from palm oil. We previously demonstrated that supplementation with TRF improved cognitive function and modulated amyloid pathology in AβPP/PS1 mice brains. The current study was designed to examine proteomic profiles underlying the therapeutic effect of TRF in the brain. Proteomic analyses were performed on samples of hippocampus, medial prefrontal cortex (mPFC), and striatum using liquid chromatography coupled to Q Exactive HF Orbitrap mass spectrometry. From these analyses, we profiled a total of 5,847 proteins of which 155 proteins were differentially expressed between AβPP/PS1 and wild-type mice. TRF supplementation of these mice altered the expression of 255 proteins in the hippocampus, mPFC, and striatum. TRF also negatively modulated the expression of amyloid beta A4 protein and receptor-type tyrosine-protein phosphatase alpha protein in the hippocampus. The expression of proteins in metabolic pathways, oxidative phosphorylation, and those involved in Alzheimer's disease were altered in the brains of AβPP/PS1 mice that received TRF supplementation.
  9. Abdul Sani NF, Amir Hamzah AIZ, Abu Bakar ZH, Mohd Yusof YA, Makpol S, Wan Ngah WZ, et al.
    Cells, 2021 06 27;10(7).
    PMID: 34199148 DOI: 10.3390/cells10071611
    The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult's susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.
  10. Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Jaafar F, et al.
    Sci Rep, 2020 06 02;10(1):8962.
    PMID: 32488024 DOI: 10.1038/s41598-020-65570-4
    Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer's disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (Aβ) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of Aβ. Mitochondrial function was shown to be affected by the increased level of Aβ and may induce cell death. Here, we aimed to compare the effects of ATF and GTF on their ability to reduce Aβ level, modulate mitochondrial function and reduce the apoptosis marker in SH-SY5Y cells stably transfected with the wild-type or mutant form of the APP gene. The Aβ level was measured by ELISA, the mitochondrial ROS and ATP level were quantified by fluorescence and luciferase assay respectively whereas the complex V enzyme activity was measured by spectrophotometry. The expressions of genes involved in the regulation of mitochondrial membrane permeability such as voltage dependent anion channel (VDAC1), adenine nucleotide translocase (ANT), and cyclophilin D (CYPD) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while the expressions of cyclophilin D (CypD), cytochrome c, Bcl2 associated X (BAX), B cell lymphoma-2 (Bcl-2), and pro-caspase-3 were determined by western blot. Our results showed that mitochondrial ROS level was elevated accompanied by decreased ATP level and complex V enzyme activity in SH-SY5Y cells expressing the mutant APP gene (p 
  11. Pahrudin Arrozi A, Shukri SNS, Mohd Murshid N, Ahmad Shahzalli AB, Wan Ngah WZ, Ahmad Damanhuri H, et al.
    Front Cell Neurosci, 2022;16:846459.
    PMID: 35614968 DOI: 10.3389/fncel.2022.846459
    The amyloid precursor protein (APP) processing pathway was altered in Alzheimer's disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundamental for AD modifying therapy. Extensive research has evaluated the protective effects of vitamin E as an antioxidant and as a signaling molecule. The present study aimed to investigate the modulatory effects of different tocopherol isomers on the expression of genes involved in regulating the APP processing pathway in vitro. The screening for the effective tocopherol isomers in reducing APP expression and Aβ-42 was carried out in SH-SY5Y stably overexpressed APP Swedish. Subsequently, quantitative one-step real-time PCR was performed to determine the modulatory effects of selected tocopherol isomers on the expression of genes in SH-SY5Y stably overexpressed three different types of APP (wild-type, APP Swedish, and APP Swedish/Indiana). Our results showed that all tocopherol isomers, especially at higher concentrations (80-100 μM), significantly increased (p < 0.05) the cell viability in all cells group, but only α-tocopherol (ATF) and γ-tocopherol (GTF) significantly decreased (p < 0.05) the APP mRNA level without statistically significant APP protein level, accompanied with a reduced significance (p < 0.05) on the level of Aβ-42 in SH-SY5Y APP Swedish. On the other hand, β- and δ-tocopherol (BTF and DTF) showed no effects on the level of APP expression and Aβ-42. Subsequent results demonstrated that ATF and GTF significantly decreased (p < 0.05) the expression of gene beta-site APP cleaving enzyme (BACE1), APH1B, and Nicastrin (NCSTN), but significantly increased (p < 0.05) the expression of Sirtuin 1 (SIRT1) in SH-SY5Y stably expressed the mutant APP form. These findings suggested that ATF and GTF could modulate altered pathways and may help ameliorate the burden of amyloid load in AD.
  12. Hanim A, Mohamed IN, Mohamed RMP, Mokhtar MH, Makpol S, Naomi R, et al.
    Nutrients, 2023 Jul 05;15(13).
    PMID: 37447362 DOI: 10.3390/nu15133036
    Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.
  13. Sani NF, Belani LK, Sin CP, Rahman SN, Das S, Chi TZ, et al.
    Biomed Res Int, 2014;2014:160695.
    PMID: 24822178 DOI: 10.1155/2014/160695
    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats.
  14. Muzammil AN, Barathan M, Yazid MD, Sulaiman N, Makpol S, Mohamed Ibrahim N, et al.
    Front Endocrinol (Lausanne), 2024;15:1406531.
    PMID: 39398330 DOI: 10.3389/fendo.2024.1406531
    Phoenixin (PNX) is an emerging neuropeptide that plays a significant role in regulating metabolism and reproduction. This comprehensive review examines findings from human, in vivo, and in vitro studies to elucidate the functions of PNX in metabolic processes. PNX has been identified as a key player in essential metabolic pathways, including energy homeostasis, glucose, lipid and electrolyte metabolism, and mitochondrial dynamics. It modulates food and fluid intake, influences glucose and lipid profiles, and affects mitochondrial biogenesis and function. PNX is abundantly expressed in the hypothalamus, where it plays a crucial role in regulating reproductive hormone secretion and maintaining energy balance. Furthermore, PNX is also expressed in peripheral tissues such as the heart, spleen, and pancreas, indicating its involvement in the regulation of metabolism across central and peripheral systems. PNX is a therapeutic peptide that operates through the G protein-coupled receptor 173 (GPR173) at the molecular level. It activates signaling pathways such as cAMP-protein kinase A (PKA) and Epac-ERK, which are crucial for metabolic regulation. Research suggests that PNX may be effective in managing metabolic disorders like obesity and type 2 diabetes, as well as reproductive health issues like infertility. Since metabolic processes are closely linked to reproduction, further understanding of PNX's role in these areas is necessary to develop effective management/treatments. This review aims to highlight PNX's involvement in metabolism and identify gaps in current knowledge regarding its impact on human health. Understanding the mechanisms of PNX's action is crucial for the development of novel therapeutic strategies for the treatment of metabolic disorders and reproductive health issues, which are significant public health concerns globally.
  15. Chin SF, Ibahim J, Makpol S, Abdul Hamid NA, Abdul Latiff A, Zakaria Z, et al.
    Nutr Metab (Lond), 2011;8(1):42.
    PMID: 21702918 DOI: 10.1186/1743-7075-8-42
    Vitamin E supplements containing tocotrienols are now being recommended for optimum health but its effects are scarcely known. The objective was to determine the effects of Tocotrienol Rich Fraction (TRF) supplementation on lipid profile and oxidative status in healthy older individuals at a dose of 160 mg/day for 6 months.
  16. Tan CM, Najib NAM, Suhaimi NF, Halid NA, Cho VV, Abdullah SI, et al.
    Arch Med Sci, 2021;17(3):752-763.
    PMID: 34025846 DOI: 10.5114/aoms.2019.85449
    Introduction: Replicative senescence results in dysregulation of cell proliferation and differentiation, which plays a role in the regenerative defects observed during age-related muscle atrophy. Vitamin E is a well-known antioxidant, which potentially ameliorates a wide range of age-related manifestations. The aim of this study was to determine the effects of tocotrienol-rich fraction (TRF) in modulating the expression of proliferation- and differentiation-associated proteins in senescent human myoblasts during the differentiation phase.

    Material and methods: Human skeletal muscle myoblasts were cultured until senescence. Young and senescent cells were treated with TRF for 24 h before and after differentiation induction, followed by evaluation of cellular morphology and efficiency of differentiation. Expression of cell proliferation marker Ki67 protein and myogenic regulatory factors MyoD and myogenin were determined.

    Results: Our findings showed that treatment with TRF significantly improved the morphology of senescent myoblasts. Promotion of differentiation was observed in young and senescent myoblasts with TRF treatment as shown by the increased fusion index and larger size of myotubes. Increased Ki67 and myogenin expression with TRF treatment was also observed in senescent myoblasts, suggesting amelioration of the myogenic program by TRF during replicative senescence.

    Conclusions: TRF modulates the expression of regulatory factors related to proliferation and differentiation in senescent human myoblasts and could be beneficial for ameliorating the regenerative defects during aging.

  17. Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Nasaruddin ML, Mori M, et al.
    J Alzheimers Dis, 2018;64(1):249-267.
    PMID: 29889072 DOI: 10.3233/JAD-170880
    We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.
  18. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, et al.
    Exp Gerontol, 2018 Oct 01;111:53-64.
    PMID: 29981398 DOI: 10.1016/j.exger.2018.07.002
    Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
  19. Razak AM, Zakaria SNA, Abdul Sani NF, Ab Rani N, Hakimi NH, Mohd Said M, et al.
    Front Pharmacol, 2023;14:1006265.
    PMID: 36843947 DOI: 10.3389/fphar.2023.1006265
    Introduction: Ginger (Zingiber officinale Roscoe) can scavenge free radicals, which cause oxidative damage and inflamm-ageing. This study aimed to evaluate the antioxidant and anti-inflammatory effects of soil ginger's sub-critical water extracts (SWE) on different ages of Sprague Dawley (SD) rats. The antioxidant properties and yield of SWE of soil- and soilless-grown ginger (soil ginger and soilless ginger will be used throughout the passage) were compared and evaluated. Methods: Three (young), nine (adult), and twenty-one (old) months old SD rats were subjected to oral gavage treatments with either distilled water or the SWE of soil ginger at a concentration of 200 mg/kg body weight (BW) for three months. Results: Soil ginger was found to yield 46% more extract than soilless ginger. While [6]-shogaol was more prevalent in soilless ginger, and [6]-gingerol concentration was higher in soil ginger (p < 0.05). Interestingly, soil ginger exhibited higher antioxidant activities than soilless ginger by using 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay. With ginger treatment, a reduced levels of tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) but not interleukin-6 (IL-6) were observed in young rats. In all ages of SD rats, ginger treatment boosted catalase activity while lowering malondialdehyde (MDA). Reduction of urine 15-isoprostane F2t in young rats, creatine kinase-MM (CK-MM) in adult and old rats and lipid peroxidation (LPO) in young and adult rats were also observed. Discussion: The findings confirmed that the SWE of both soil and soilless grown ginger possessed antioxidant activities. Soil ginger produced a higher yield of extracts with a more prominent antioxidant activity. The SWE of soil ginger treatment on the different ages of SD rats ameliorates oxidative stress and inflammation responses. This could serve as the basis for developing a nutraceutical that can be used as a therapeutic intervention for ageing-related diseases.
  20. Abu Bakar ZH, Damanhuri HA, Makpol S, Wan Kamaruddin WMA, Abdul Sani NF, Amir Hamzah AIZ, et al.
    J Alzheimers Dis, 2019;70(s1):S43-S62.
    PMID: 30594926 DOI: 10.3233/JAD-180511
    BACKGROUND: Many studies on biochemical and psychological variables have aimed to elucidate the association between aging and cognitive function. Demographic differences and protein expression have been reported to play a role in determining the cognitive capability of a population.

    OBJECTIVE: This study aimed to determine the effect of age on the protein profile of Malay individuals and its association with cognitive competency.

    METHODS: A total of 160 individuals were recruited and grouped accordingly. Cognitive competency of each subject was assessed with several neuropsychological tests. Plasma samples were collected and analyzed with Q Exactive HF Orbitrap. Proteins were identified and quantitated with MaxQuant and further analyzed with Perseus to determine differentially expressed proteins. PANTHER, Reactome, and STRING were applied for bioinformatics output.

    RESULTS: Our data showed that the Malay individuals are vulnerable to the deterioration of cognitive function with aging, and most of the proteins were differentially expressed in concordance. Several physiological components and pathways were shown to be involved, giving a hint of a promising interpretation on the induction of aging toward the state of the Malays' cognitive function. Nevertheless, some proteins have shown a considerable interaction with the generated protein network, which provides a direction of focus for further investigation.

    CONCLUSION: This study demonstrated notable changes in the expression of several proteins as age increased. These changes provide a promising platform for understanding the biochemical factors affecting cognitive function in the Malay population. The exhibited network of protein-protein interaction suggests the possibility of implementing regulatory intervention in ameliorating Malay cognitive function.

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