Displaying publications 61 - 80 of 97 in total

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  1. Long-term in vitro expansion of human adipose-derived stem cells showed low risk of tumourigenicity
    Zaman WS, Makpol S, Sathapan S, Chua KH
    J Tissue Eng Regen Med, 2014 Jan;8(1):67-76.
    PMID: 22552847 DOI: 10.1002/term.1501
    In the field of cell-based therapy and regenerative medicine, clinical application is the ultimate goal. However, one major concern is: does in vitro manipulation during culture expansion increases tumourigenicity risk on the prepared cells? Therefore, the aim of this study was to investigate the effect of long-term in vitro expansion on human adipose-derived stem cells (ASCs). The ASCs were harvested from lipo-aspirate samples and cultured until passage 20 (P20), using standard culture procedures. ASCs at P5, P10, P15 and P20 were analysed for morphological changes, DNA damage (Comet assay), tumour suppressor gene expression level (quantitative PCR), p53 mutation, telomerase activity, telomere length determination and in vivo tumourigenicity test. Our data showed that ASCs lost their fibroblastic feature in long-term culture. The population doubling time of ASCs increased with long-term culture especially at P15 and P20. There was an increase in DNA damage at later passages (P15 and P20). No significant changes were observed in both p53 and p21 genes expression throughout the long-term culture. There was also no p53 mutation detected and no significant changes were recorded in the relative telomerase activity (RTA) and mean telomere length (TRF) in ASCs at all passages. In vivo implantation of ASCs at P15 and P20 into the nude mice did not result in tumour formation after 4 months. The data showed that ASCs have low risk of tumourigenicity up to P20, with a total population doubling of 42 times. This indicates that adipose tissue should be a safe source of stem cells for cell-based therapy.
  2. Does gamma irradiation affect physicochemical properties of honey?
    Hussein SZ, Yusoff KM, Makpol S, Mohd Yusof YA
    Clin Ter, 2014;165(2):e125-33.
    PMID: 24770820 DOI: 10.7471/CT.2014.1695
    Honey is a supersaturated solution of sugars, enriched with proteins, minerals, vitamins, organic acids and polyphenols. Gamma irradiation is a physical technique of food preservation which protects the honey from insects' and microbial contamination during storage. We investigated the effect of gamma irradiation on physicochemical properties in two types of Malaysian honey, Gelam and Nenas.
  3. Comparable down-regulation of TYR, TYRP1 and TYRP2 genes and inhibition of melanogenesis by tyrostat, tocotrienol-rich fraction and tocopherol in human skin melanocytes improves skin pigmentation
    Makpol S, Jam FA, Rahim NA, Khor SC, Ismail Z, Yusof YA, et al.
    Clin Ter, 2014;165(1):e39-45.
    PMID: 24589959
    Antioxidant has been recognized to inhibit UV-induced melanogenesis. This study aimed to elucidate the molecular mechanism of tyrostat, tocopherol and tocotrienol-rich fraction in inhibiting melanogenesis in human skin melanocytes.
  4. Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts
    Durani LW, Jaafar F, Tan JK, Tajul Arifin K, Mohd Yusof YA, Wan Ngah WZ, et al.
    Clin Ter, 2016;166(6):e365-73.
    PMID: 26794818 DOI: 10.7417/T.2015.1902
    Tocotrienols have been known for their antioxidant properties besides their roles in cellular signalling, gene expression, immune response and apoptosis. This study aimed to determine the molecular mechanism of tocotrienol-rich fraction (TRF) in preventing cellular senescence of human diploid fibroblasts (HDFs) by targeting the genes in senescence-associated signalling pathways.
  5. Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways
    Khor SC, Mohd Yusof YA, Wan Ngah WZ, Makpol S
    Clin Ter, 2015;166(2):e81-90.
    PMID: 25945449 DOI: 10.7417/CT.2015.1825
    BACKGROUND AND OBJECTIVE: Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).

    MATERIALS AND METHODS: Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.

    RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.

    CONCLUSIONS: Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging.

  6. Chlorella vulgaris modulates the expression of senescence-associated genes in replicative senescence of human diploid fibroblasts
    Jaafar F, Durani LW, Makpol S
    Mol Biol Rep, 2020 Jan;47(1):369-379.
    PMID: 31642042 DOI: 10.1007/s11033-019-05140-8
    Human diploid fibroblasts (HDFs) cultured in vitro have limited capacity to proliferate after population doubling is repeated several times, and they enter into a state known as replicative senescence or cellular senescence. This study aimed to investigate the effect of Chlorella vulgaris on the replicative senescence of HDFs by determining the expression of senescence-associated genes. Young and senescent HDFs were divided into untreated control and C. vulgaris-treated groups. A senescence-associated gene transcription analysis was carried out with qRT-PCR. Treatment of young HDFs with C. vulgaris reduced the expression of SOD1, CAT and CCS (p 
  7. Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases
    Abdullah A, Mohd Murshid N, Makpol S
    Mol Neurobiol, 2020 Dec;57(12):5193-5207.
    PMID: 32865663 DOI: 10.1007/s12035-020-02083-1
    In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease is highlighted.
  8. Fulltext Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells
    Rahman AA, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2014 Sep 12;19(9):14528-41.
    PMID: 25221872 DOI: 10.3390/molecules190914528
    Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.
  9. Fulltext Gelam honey protects against gamma-irradiation damage to antioxidant enzymes in human diploid fibroblasts
    Ahmad TA, Jubri Z, Rajab NF, Rahim KA, Yusof YA, Makpol S
    Molecules, 2013 Feb 11;18(2):2200-11.
    PMID: 23434870 DOI: 10.3390/molecules18022200
    The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma rays at the dose rate of 0.25 Gy/min. Gamma-irradiation was shown to down-regulate SOD1, SOD2, CAT and GPx1 gene expressions (p < 0.05). Conversely, HDFs treated with Gelam honey alone showed up-regulation of all genes studied. Similarly, SOD, CAT and GPx enzyme activities in HDFs decreased with gamma-irradiation and increased when cells were treated with Gelam honey (p < 0.05). Furthermore, of the three different stages of study treatment, pre-treatment with Gelam honey caused up-regulation of SOD1, SOD2 and CAT genes expression and increased the activity of SOD and CAT. As a conclusion, Gelam honey modulates the expression of antioxidant enzymes at gene and protein levels in irradiated HDFs indicating its potential as a radioprotectant agent.
  10. Fulltext γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells
    Yusof KM, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2015 Jun 03;20(6):10280-97.
    PMID: 26046324 DOI: 10.3390/molecules200610280
    Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
  11. Fulltext Antioxidant capacities and total phenolic contents increase with gamma irradiation in two types of Malaysian honey
    Hussein SZ, Yusoff KM, Makpol S, Yusof YA
    Molecules, 2011 Jul 27;16(8):6378-95.
    PMID: 21796076 DOI: 10.3390/molecules16066378
    Two types of monofloral Malaysian honey (Gelam and Nenas) were analyzed to determine their antioxidant activities and total phenolic and flavonoid contents, with and without gamma irradiation. Our results showed that both types of honey can scavenge free radicals and exhibit high antioxidant-reducing power; however, Gelam honey exhibited higher antioxidant activity (p < 0.05) than Nenas honey, which is in good correlation (r = 0.9899) with its phenolic contents. Interestingly, we also noted that both irradiated honeys have higher antioxidant activities and total phenolic and flavonoid contents compared to nonirradiated honeys by Folin-Ciocalteu and UV-spectrophotometry methods, respectively. However, HPLC analysis for phenolic compounds showed insignificant increase between irradiated and nonirradiated honeys. The phenolic compounds such as: caffeic acid, chlorogenic acid, ellagic acid, p- coumaric acid, quercetin and hesperetin as indicated by HPLC method were found to be higher in Gelam honey versus Nenas honey. In conclusion, irradiation of honey causes enhanced antioxidant activities and flavonoid compounds.
  12. Fulltext Zebrafish: A Pharmacological Model for Learning and Memory Research
    Tan JK, Nazar FH, Makpol S, Teoh SL
    Molecules, 2022 Oct 30;27(21).
    PMID: 36364200 DOI: 10.3390/molecules27217374
    Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.
  13. Fulltext Suppression of Inflamm-Aging by Moringa oleifera and Zingiber officinale Roscoe in the Prevention of Degenerative Diseases: A Review of Current Evidence
    Mohd Sahardi NFN, Makpol S
    Molecules, 2023 Aug 03;28(15).
    PMID: 37570837 DOI: 10.3390/molecules28155867
    Inflammation or inflamm-aging is a chronic low-grade inflammation that contributes to numerous types of degenerative diseases among the elderly and might be impeded by introducing an anti-inflammatory agent like Moringa oleifera Lam (moringa) and Zingiber officinale Roscoe (ginger). Therefore, this paper aims to review the role of moringa and ginger in suppressing inflamm-aging to prevent degenerative diseases. Various peer-reviewed publications were searched and downloaded using the reputed search engine "Pubmed" and "Google Scholar". These materials were reviewed and tabulated. A comparison between these previous findings was made based on the mechanism of action of moringa and ginger against degenerative diseases, focusing on their anti-inflammatory properties. Many studies have reported the efficacy of moringa and ginger in type 2 diabetes mellitus, neurodegenerative disease, cardiovascular disease, cancer, and kidney disease by reducing inflammatory cytokines activities, mainly of TNF-α and IL-6. They also enhanced the activity of antioxidant enzymes, including catalase, glutathione, and superoxide dismutase. The anti-inflammatory activities can be seen by inhibiting NF-κβ activity. Thus, the anti-inflammatory potential of moringa and ginger in various types of degenerative diseases due to inflamm-aging has been shown in many recent types of research.
  14. Fulltext Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review
    Yap KH, Azmin S, Makpol S, Damanhuri HA, Mustapha M, Hamzah JC, et al.
    Neural Regen Res, 2023 Jun;18(6):1179-1185.
    PMID: 36453391 DOI: 10.4103/1673-5374.360164
    Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.
  15. Fulltext Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model
    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.
  16. Fulltext Elucidating the Pharmacological Properties of Zingiber officinale Roscoe (Ginger) on Muscle Ageing by Untargeted Metabolomic Profiling of Human Myoblasts
    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.
  17. Fulltext Tocotrienol rich fraction supplementation improved lipid profile and oxidative status in healthy older adults: A randomized controlled study
    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.
  18. Fulltext Combined ginger extract & Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells
    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.
  19. Fulltext Expression of senescence-associated microRNAs and target genes in cellular aging and modulation by tocotrienol-rich fraction
    Khee SG, Yusof YA, Makpol S
    Oxid Med Cell Longev, 2014;2014:725929.
    PMID: 25132913 DOI: 10.1155/2014/725929
    Emerging evidences highlight the implication of microRNAs as a posttranscriptional regulator in aging. Several senescence-associated microRNAs (SA-miRNAs) are found to be differentially expressed during cellular senescence. However, the role of dietary compounds on SA-miRNAs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on SA-miRNAs (miR-20a, miR-24, miR-34a, miR-106a, and miR-449a) and established target genes of miR-34a (CCND1, CDK4, and SIRT1) during replicative senescence of human diploid fibroblasts (HDFs). Primary cultures of HDFs at young and senescent were incubated with TRF at 0.5 mg/mL. Taqman microRNA assay showed significant upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in senescent HDFs (P < 0.05). TRF reduced miR-34a expression in senescent HDFs and increased miR-20a expression in young HDFs and increased miR-449a expression in both young and senescent HDFs. Our results also demonstrated that ectopic expression of miR-34a reduced the expression of CDK4 significantly (P < 0.05). TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene expression. No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol-rich fraction prevented cellular senescence of human diploid fibroblasts via modulation of SA-miRNAs and target genes expression.
  20. Fulltext Vitamin E in sarcopenia: current evidences on its role in prevention and treatment
    Khor SC, Abdul Karim N, Ngah WZ, Yusof YA, Makpol S
    Oxid Med Cell Longev, 2014;2014:914853.
    PMID: 25097722 DOI: 10.1155/2014/914853
    Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies.
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