Displaying publications 61 - 80 of 91 in total

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  1. Hamid A, Rajab NF, Charmagne Y, Awang N, Jufri NF, Rasli NR
    Anticancer Agents Med Chem, 2024;24(1):58-65.
    PMID: 37921147 DOI: 10.2174/0118715206266851231025054446
    INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell).

    METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes.

    RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 μM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 μM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects.

    CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.

  2. Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF
    Sci Rep, 2021 Nov 18;11(1):22500.
    PMID: 34795360 DOI: 10.1038/s41598-021-01988-8
    Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P 
  3. Ng PL, Rajab NF, Then SM, Mohd Yusof YA, Wan Ngah WZ, Pin KY, et al.
    J Zhejiang Univ Sci B, 2014 Aug;15(8):692-700.
    PMID: 25091987 DOI: 10.1631/jzus.B1300303
    OBJECTIVE: The combination effect of Piper betle (PB) and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated.
    METHODS: HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography (HPLC) was performed to exclude any possible chemical interaction between the compounds.
    RESULTS: In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose (IC50 12.5 µmol/L) and a shorter time (24 h) in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively.
    CONCLUSIONS: In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
    KEYWORDS: 5-Fluorouracil; Herb-drug interaction; Isobologram analysis; Piper betle L.; Piperaceae
  4. Yen HK, Fauzi AR, Din LB, McKelvey-Martin VJ, Meng CK, Inayat-Hussain SH, et al.
    PMID: 25107315 DOI: 10.1186/1472-6882-14-295
    Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer's disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4.
  5. Inayat-Hussain SH, Chan KM, Rajab NF, Din LB, Chow SC, Kizilors A, et al.
    Toxicol Lett, 2010 Mar 1;193(1):108-14.
    PMID: 20026395 DOI: 10.1016/j.toxlet.2009.12.010
    Goniothalamin (GTN) isolated from Goniothalamus sp. has been demonstrated to induce apoptosis in a variety of cancer cell lines including Jurkat T leukemia cells. However, the mechanism of GTN-induced apoptosis upstream of mitochondria is still poorly defined. In this study, GTN caused a decrease in GSH with an elevation of reactive oxygen species as early as 30 min and DNA damage as assessed by Comet assay. Analysis using topoisomerase II processing of supercoiled pBR 322 DNA showed that GTN caused DNA damage via a topoisomerase II-independent pathway suggesting that cellular oxidative stress may contribute to genotoxicity. A 12-fold increase of caspase-2 activity was observed in GTN-treated Jurkat cells after 4h treatment and this was confirmed using Western blotting. Although the caspase-2 inhibitor Z-VDVAD-FMK inhibited the proteolytic activity of caspase-2, apoptosis ensued confirming that caspase-2 activity was not crucial for GTN-induced apoptosis. However, GTN-induced apoptosis was completely abrogated by N-acetylcysteine further confirming the role of oxidative stress. Since cytochrome c release was observed as early as 1h without any appreciable change in Bcl-2 protein expression, we further investigated whether overexpression of Bcl-2 confers resistance in GTN-induced cytotoxicity. Using a panel of Jurkat Bcl-2 transfectants, GTN cytotoxicity was not abrogated in these cells. In conclusion, GTN induces DNA damage and oxidative stress resulting in apoptosis which is independent of both caspase-2 and Bcl-2.
  6. Taib IS, Budin SB, Siti Nor Ain SM, Mohamed J, Louis SR, Das S, et al.
    J Zhejiang Univ Sci B, 2009 Nov;10(11):813-9.
    PMID: 19882755 DOI: 10.1631/jzus.B0920199
    Litsea elliptica Blume leaves have been traditionally used as medicinal herbs because of its antimutagenicity, chemopreventative and insecticidal properties. In this study, the toxic effects of L. elliptica essential oil against Sprague-Dawley rat's red blood cells (RBCs) were evaluated. L. elliptica essential oil was given by oral gavage 5 times per week for 3 treated groups in the doses of 125, 250, and 500 mg/(kg body weight), respectively, and the control group received distilled water. Full blood count, RBC osmotic fragility, RBC morphological changes, and RBC membrane lipid were analyzed 28 d after the treatment. Although L. elliptica essential oil administration had significantly different effects on hemoglobin (Hb), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), and mean cell hemoglobin (MCH) in the experimental groups as compared to the control group (P<0.05), the values were still within the normal range. L. elliptica induced morphological changes of RBC into the form of echinocyte. The percentage of echinocyte increased significantly among the treated groups in a dose-response manner (P<0.001). The concentrations of RBC membrane phospholipids and cholesterol of all treated groups were significantly lower than those of control group (P<0.001). However, the RBC membrane osmotic fragility and total proteins of RBC membrane findings did not differ significantly between control and treated groups (P>0.05). It is concluded that structural changes in the RBC membrane due to L. elliptica essential oil administration did not cause severe membrane damage.
  7. Chan KM, Hamzah R, Rahaman AA, Jong VY, Khong HY, Rajab NF, et al.
    Food Chem Toxicol, 2012 Aug;50(8):2916-22.
    PMID: 22613213 DOI: 10.1016/j.fct.2012.04.048
    Inophyllin A (INO-A), a pyranoxanthone isolated from the roots of Calophyllum inophyllum represents a new xanthone with potential chemotherapeutic activity. In this study, the molecular mechanism of INO-A-induced cell death was investigated in Jurkat T lymphoblastic leukemia cells. Assessment of phosphatidylserine exposure confirmed apoptosis as the primary mode of cell death in INO-A-treated Jurkat cells. INO-A treatment for only 30 min resulted in a significant increase of tail moment which suggests that DNA damage is an early apoptotic signal. Further flow cytometric assessment of the superoxide anion level confirmed that INO-A induced DNA damage was mediated with a concomitant generation of reactive oxygen species (ROS). Investigation on the thiols revealed an early decrease of free thiols in 30 min after 50 μM INO-A treatment. Using tetramethylrhodamine ethyl ester, a potentiometric dye, the loss of mitochondrial membrane potential (MPP) was observed in INO-A-treated cells as early as 30 min. The INO-A-induced apoptosis progressed with the simultaneous activation of caspases-2 and -9 which then led to the processing of caspase-3. Taken together, these data demonstrate that INO-A induced early oxidative stress, DNA damage and loss of MMP which subsequently led to the activation of an intrinsic pathway of apoptosis in Jurkat cells.
  8. You YX, Shahar S, Rajab NF, Haron H, Yahya HM, Mohamad M, et al.
    Nutrients, 2021 Jan 29;13(2).
    PMID: 33572715 DOI: 10.3390/nu13020434
    Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.
  9. Vanoh D, Shahar S, Yahya HM, Che Din N, Mat Ludin AF, Ajit Singh DK, et al.
    Clin Interv Aging, 2021;16:161-175.
    PMID: 33531799 DOI: 10.2147/CIA.S266587
    Purpose: Use of dietary supplements by older adults has been increasing for improving micronutrient deficiencies, cognitive function, and overall health status. Thus, the objective of this secondary investigation is to explore the longitudinal association of baseline supplement intake in improving cognitive function, biochemical parameters, anthropometric variables and physical fitness among older adults.

    Methods: Towards Useful Aging (TUA) is a three-year longitudinal study conducted at baseline (2013-2014) and at follow-up (2015-2017) surveys. The number of participants dropped from 2322 during baseline study to 1787 and 1560 during the 18th and 36th month follow-up, respectively. Data on socio-demography, use of dietary supplement, biochemical indices, anthropometry, cognitive function, physical fitness and depressive symptoms were obtained. Longitudinal associations were done using the linear mixed model analysis among 1285 subjects with complete data.

    Results: The most common vitamin and mineral supplementations consumed were multivitamin, B-complex, and calcium. Meanwhile, the herbal supplements consumed by participants were Eurycoma longifolia, Morinda citrifolia and Orthosiphon aristatus. Longitudinal analysis adjusted for multiple covariates showed improvement in both supplement users and non-users for global cognitive function, working memory, visual memory, 2-minute step test, chair stand test, chair sit and reach and time up and go test, waist circumference and hip circumference in both the supplement users and non-users.

    Conclusion: Our findings indicated that dietary supplement intake is not associated with cognitive function, physical fitness, nutritional status, depressive symptoms or biochemical indices since improvement in the parameters was observed among both supplement users and non-users.

  10. Ooi TC, Ibrahim FW, Ahmad S, Chan KM, Leong LM, Mohammad N, et al.
    Molecules, 2021 May 29;26(11).
    PMID: 34072474 DOI: 10.3390/molecules26113287
    Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5-100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.
  11. Nor Hisam NS, Ugusman A, Rajab NF, Ahmad MF, Fenech M, Liew SL, et al.
    Pharmaceutics, 2021 Aug 28;13(9).
    PMID: 34575429 DOI: 10.3390/pharmaceutics13091353
    Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family and has a high affinity towards pro-survival BCL-2 family proteins (i.e., BCL-XL, BCL-2, BCL-W) to induce cell apoptosis effectively. A single navitoclax action potently ameliorates several tumor progressions, including blood and bone marrow cancer, as well as small cell lung carcinoma. Not only that, but navitoclax alone also therapeutically affects fibrotic disease. Nevertheless, outcomes from the clinical trial of a single navitoclax agent in patients with advanced and relapsed small cell lung cancer demonstrated a limited anti-cancer activity. This brings accumulating evidence of navitoclax to be used concomitantly with other chemotherapeutic agents in several solid and non-solid tumors that are therapeutically benefiting from navitoclax treatment in preclinical studies. Initially, we justify the anti-cancer role of navitoclax in combination therapy. Then, we evaluate the current evidence of navitoclax in combination with the chemotherapeutic agents comprehensively to indicate the primary regulator of this combination strategy in order to produce a therapeutic effect.
  12. Ng CT, Fong LY, Tan JJ, Rajab NF, Abas F, Shaari K, et al.
    BMC Complement Altern Med, 2018 Jul 06;18(1):210.
    PMID: 29980198 DOI: 10.1186/s12906-018-2270-1
    BACKGROUND: Clinacanthus nutans (Burm. f.) Lindau. has traditionally been using in South East Asia countries to manage cancer. However, scientific evidence is generally lacking to support this traditional claim. This study aims to investigate the in vitro, ex-vivo and in vivo effects of C. nutans extracts on angiogenesis.

    METHODS: C. nutans leaves was extracted with 50-100% ethanol or deionised water at 1% (w/v). Human umbilical veins endothelial cell (HUVEC) proliferation was examined using MTT assay. The in vitro anti-angiogenic effects of C. nutans were assessed using wound scratch, tube formation and transwell migration assays. The VEGF levels secreted by human oral squamous cell carcinoma (HSC-4) cell and HUVEC permeability were also measured. Besides, the rat aortic ring and chick embryo chorioallantoic membrane (CAM) assays, representing ex vivo and in vivo models, respectively, were performed.

    RESULTS: The MTT assay revealed that water extract of C. nutans leaves exhibited the highest activity, compared to the ethanol extracts. Therefore, the water extract was chosen for subsequent experiments. C. nutans leaf extract significantly suppressed endothelial cell proliferation and migration in both absence and presence of VEGF. However, the water extract failed to suppress HUVEC transmigration, differentiation and permeability. C. nutans water extract also did not suppress HSC-4 cell-induced VEGF production. Importantly, C. nutans water extract significantly abolished the sprouting of vessels in aortic rings as well as in chick embryo CAM.

    CONCLUSION: In conclusion, these findings reveal potential anti-angiogenic effects of C. nutans, providing new evidence for its potential application as an anti-angiogenic agent.

  13. Ooi TC, Ishak WS, Sharif R, Shahar S, Rajab NF, Singh DKA, et al.
    Clin Interv Aging, 2021;16:2033-2046.
    PMID: 34949916 DOI: 10.2147/CIA.S340432
    Purpose: This study evaluates the prevalence of and the multidimensional risk factors associated with age-related hearing loss (ARHL) among community-dwelling older adults in Malaysia.

    Patients and Methods: A total of 253 participants aged 60 years and above participated in this cross-sectional study. The participants were subjected to pure tone audiometric assessment. The hearing threshold was calculated for the better ear and classified into pure-tone average (PTA) for the octave frequencies from 0.5 to 4 kHz and high-frequency pure-tone average (HFA) for the octave from 2 to 8kHz. Then, the risk factors associated with PTA hearing loss (HL) and HFAHL were identified by using multivariate logistic regression analysis.

    Results: The prevalence of ARHL based on PTA and HFA among the community-dwelling older adults was 75.5% and 83.0%, respectively. Following multifactorial adjustments, being older (OR: 1.239; 95% CI: 1.062-1.445), having higher waist circumference (OR: 1.158; 95% CI: 1.015-1.322), lower intake of niacin (OR: 0.909; 95% CI: 0.831-0.988) and potassium (OR: 0.998; 95% CI: 0.996-1.000), and scoring lower in RAVLT T5 (OR: 0.905; 95% CI: 0.838-0.978) were identified as the risk factors of PTAHL. Meanwhile, being older (OR: 1.117; 95% CI: 1.003-1.244), higher intake of carbohydrate (OR: 1.018; 95% CI: 1.006-1.030), lower intake of potassium (OR: 0.998; 95% CI: 0.997-0.999), and lower scores on the RAVLT T5 (OR: 0.922; 95% CI: 0.874-0.973) were associated with increased risk of having HFAHL.

    Conclusion: Increasing age, having higher waist circumference, lower intake of niacin and potassium, higher intake of carbohydrates and having lower RAVLT T5 score were associated with increased risk of ARHL. Modifying these risk factors may be beneficial in preventive and management strategies of ARHL among older persons.

  14. Rivan NFM, Singh DKA, Shahar S, Wen GJ, Rajab NF, Din NC, et al.
    BMC Geriatr, 2021 10 25;21(1):593.
    PMID: 34696720 DOI: 10.1186/s12877-021-02525-y
    BACKGROUND: Cognitive frailty, a combination of physical frailty and cognitive impairment, is associated with functional decline in older adults. However, there is limited information if cognitive frailty predicts the incidence of falls, injuries, and disability. In this study, we aimed to determine the ability of cognitive frailty in predicting the incidence of falls, injuries and disability among multi-ethnic older adults in Malaysia at 5 years follow-up.

    METHODS: In this prospective cohort study, a total of 400 participants aged 60 years and above were successfully followed up at 5 years. Participants' socio-demographic, medical history, psycho-social, physical, cognitive and dietary intake information was obtained. Cognitive frailty was defined as comorbid physical frailty (> 1 Fried criteria) and mild cognitive impairment (Petersen criteria). Univariate analysis was performed for all variables, followed by hierarchical binary logistic regression (BLR) analysis to identify the ability of CF in predicting the incidence of falls, injuries, and disability. The significant value was set at p 

  15. Ooi TC, Nordin FJ, Rahmat NS, Abdul Halim SN', Sarip R, Chan KM, et al.
    PMID: 36868695 DOI: 10.1016/j.mrgentox.2022.503581
    Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 μM, 2.70 ± 0.17 μM, 1.34 ± 0.22 μM, 2.82 ± 0.45 μM, and 0.64 ± 0.04 μM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.
  16. Joseph DK, Mat Ludin AF, Ibrahim FW, Ahmadazam A, Che Roos NA, Shahar S, et al.
    Front Physiol, 2023;14:1287170.
    PMID: 37817985 DOI: 10.3389/fphys.2023.1287170
    [This corrects the article DOI: 10.3389/fphys.2023.1216948.].
  17. Joseph DK, Mat Ludin AF, Ibrahim FW, Ahmadazam A, Che Roos NA, Shahar S, et al.
    Front Physiol, 2023;14:1216948.
    PMID: 37664425 DOI: 10.3389/fphys.2023.1216948
    Introduction: Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately. Methods: Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS. Results: A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis. Discussion: The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments. Systematic Review Registration: identifier: [CRD42021271001].
  18. Malek Rivan NF, Shahar S, Rajab NF, Singh DKA, Din NC, Hazlina M, et al.
    Clin Interv Aging, 2019;14:1343-1352.
    PMID: 31413555 DOI: 10.2147/CIA.S211027
    PURPOSE: This study was aimed at determining the presence of cognitive frailty and its associated factors among community-dwelling older adults from the "LRGS-Towards Useful Aging (TUA)" longitudinal study.

    PATIENTS AND METHODS: The available data related to cognitive frailty among a sub-sample of older adults aged 60 years and above (n=815) from two states in Malaysia were analysed. In the LRGS-TUA study, a comprehensive interview-based questionnaire was administered to obtain the socio-demographic information of the participants, followed by assessments to examine the cognitive function, functional status, dietary intake, lifestyle, psychosocial status and biomarkers associated with cognitive frailty. The factors associated with cognitive frailty were assessed using a bivariate logistic regression (BLR).

    RESULTS: The majority of the older adults were categorized as robust (68.4%), followed by cognitively pre-frail (37.4%) and cognitively frail (2.2%). The data on the cognitively frail and pre-frail groups were combined for comparison with the robust group. A hierarchical BLR indicated that advancing age (OR=1.04, 95% CI:1.01-1.08, p<0.05) and depression (OR=1.49, 95% CI:1.34-1.65, p<0.001) scored lower on the Activity of Daily Living (ADL) scale (OR=0.98, 95% CI:0.96-0.99, p<0.05), while low social support (OR=0.98, 95% CI:0.97-0.99, p<0.05) and low niacin intake (OR=0.94, 95% CI:0.89-0.99, p<0.05) were found to be significant factors for cognitive frailty. Higher oxidative stress (MDA) and lower telomerase activity were also associated with cognitive frailty (p<0.05).

    CONCLUSION: Older age, a lower niacin intake, lack of social support, depression and lower functional status were identified as significant factors associated with cognitive frailty among older Malaysian adults. MDA and telomerase activity can be used as potential biomarkers for the identification of cognitive frailty.

  19. Inayat-Hussain SH, Wong LT, Chan KM, Rajab NF, Din LB, Harun R, et al.
    Toxicol Lett, 2009 Dec 15;191(2-3):118-22.
    PMID: 19698770 DOI: 10.1016/j.toxlet.2009.08.012
    Goniothalamin, a styryllactone, has been shown to induce cytotoxicity via apoptosis in several tumor cell lines. In this study, we have examined the potential role of several genes, which were stably transfected into T-cell lines and which regulate apoptosis in different ways, on goniothalamin-induced cell death. Overexpression of full-length receptor for activated protein C-kinase 1 (RACK-1) and pc3n3, which up-regulates endogenous RACK-1, in both Jurkat and W7.2 T cells resulted in inhibition of goniothalamin-induced cell death as assessed by MTT and clonogenic assays. However, overexpression of rFau (antisense sequence to Finkel-Biskis-Reilly murine sarcoma virus-associated ubiquitously expressed gene) in W7.2 cells did not confer resistance to goniothalamin-induced cell death. Etoposide, a clinically used cytotoxic agent, was equipotent in causing cytotoxicity in all the stable transfectants. Assessment of DNA damage by Comet assay revealed goniothalamin-induced DNA strand breaks as early as 1 h in vector control but this effect was inhibited in RACK-1 and pc3n3 stably transfected W7.2 cells. This data demonstrate that RACK-1 plays a crucial role in regulating cell death signalling pathways induced by goniothalamin.
  20. Muniandy S, Yahya HM, Shahar S, Kamisan Atan I, Mahdy ZA, Rajab NF, et al.
    BMJ Open, 2023 Nov 01;13(11):e073323.
    PMID: 37914304 DOI: 10.1136/bmjopen-2023-073323
    INTRODUCTION: Eurycoma longifolia Jack (EL), profoundly recognised as 'Tongkat Ali', is a medicinal herb originating from Southeast Asia. It is commonly used in traditional 'antiageing' treatments to address decreased energy, mood, libido and hormonal imbalances. While the benefits of EL have been extensively studied among the male population, less attention has been given to its effects on women. Menopause can impact the overall well-being of middle-aged women and incorporation of herbal supplements can aid them in managing the menopausal symptoms.

    METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis.

    ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications.

    TRIAL REGISTRATION NUMBER: ACTRN12622001341718.

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