Displaying publications 1 - 20 of 67 in total

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  1. Fulltext gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals
    Makpol S, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ
    Oxid Med Cell Longev, 2010 Jan-Feb;3(1):35-43.
    PMID: 20716926 DOI: 10.4161/oxim.3.1.9940
    The effects of palm gamma-tocotrienol (GGT) on oxidative stress-induced cellular ageing was investigated in normal human skin fibroblast cell lines derived from different age groups; young (21-year-old, YF), middle (40-year-old, MF) and old (68-year-old, OF). Fibroblast cells were treated with gamma-tocotrienol for 24 hours before or after incubation with IC50 dose of H2O2 for 2 hours. Changes in cell viability, telomere length and telomerase activity were assessed using the MTS assay (Promega, USA), Southern blot analysis and telomere repeat amplification protocol respectively. Results showed that treatment with different concentrations of gamma-tocotrienol increased fibroblasts viability with optimum dose of 80 microM for YF and 40 microM for both MF and OF. At higher concentrations, gamma-tocotrienol treatment caused marked decrease in cell viability with IC50 value of 200 microM (YF), 300 microM (MF) and 100 microM (OF). Exposure to H2O2 decreased cell viability in dose dependent manner, shortened telomere length and reduced telomerase activity in all age groups. The IC50 of H2O2 was found to be; YF (700 microM), MF (400 microM) and OF (100 microM). Results showed that viability increased significantly (p < 0.05) when cells were treated with 80 microM and 40 microM gamma-tocotrienol prior or after H2O2-induced oxidative stress in all age groups. In YF and OF, pretreatment with gamma-tocotrienol prevented shortening of telomere length and reduction in telomerase activity. In MF, telomerase activity increased while no changes in telomere length was observed. However, post-treatment of gamma-tocotrienol did not exert any significant effects on telomere length and telomerase activity. Thus, these data suggest that gamma-tocotrienol protects against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase.
  2. 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.
  3. Fulltext Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure
    Tang SP, Kuttulebbai Nainamohamed Salam S, Jaafar H, Gan SH, Muzaimi M, Sulaiman SA
    Oxid Med Cell Longev, 2017;2017:4605782.
    PMID: 28127418 DOI: 10.1155/2017/4605782
    Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
  4. Fulltext Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats
    Azman KF, Zakaria R, Abdul Aziz CB, Othman Z
    Oxid Med Cell Longev, 2016;2016:1549158.
    PMID: 27119005 DOI: 10.1155/2016/1549158
    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.
  5. Fulltext Tocotrienol-Rich Fraction Ameliorates Antioxidant Defense Mechanisms and Improves Replicative Senescence-Associated Oxidative Stress in Human Myoblasts
    Khor SC, Wan Ngah WZ, Mohd Yusof YA, Abdul Karim N, Makpol S
    Oxid Med Cell Longev, 2017;2017:3868305.
    PMID: 28243354 DOI: 10.1155/2017/3868305
    During aging, oxidative stress affects the normal function of satellite cells, with consequent regeneration defects that lead to sarcopenia. This study aimed to evaluate tocotrienol-rich fraction (TRF) modulation in reestablishing the oxidative status of myoblasts during replicative senescence and to compare the effects of TRF with other antioxidants (α-tocopherol (ATF) and N-acetyl-cysteine (NAC)). Primary human myoblasts were cultured to young, presenescent, and senescent phases. The cells were treated with antioxidants for 24 h, followed by the assessment of free radical generation, lipid peroxidation, antioxidant enzyme mRNA expression and activities, and the ratio of reduced to oxidized glutathione. Our data showed that replicative senescence increased reactive oxygen species (ROS) generation and lipid peroxidation in myoblasts. Treatment with TRF significantly diminished ROS production and decreased lipid peroxidation in senescent myoblasts. Moreover, the gene expression of superoxide dismutase (SOD2), catalase (CAT), and glutathione peroxidase (GPX1) was modulated by TRF treatment, with increased activity of superoxide dismutase and catalase and reduced glutathione peroxidase in senescent myoblasts. In comparison to ATF and NAC, TRF was more efficient in heightening the antioxidant capacity and reducing free radical insults. These results suggested that TRF is able to ameliorate antioxidant defense mechanisms and improves replicative senescence-associated oxidative stress in myoblasts.
  6. Fulltext Tocotrienol-Rich Fraction (TRF) Treatment Promotes Proliferation Capacity of Stress-Induced Premature Senescence Myoblasts and Modulates the Renewal of Satellite Cells: Microarray Analysis
    Lim JJ, Wan Zurinah WN, Mouly V, Norwahidah AK
    Oxid Med Cell Longev, 2019;2019:9141343.
    PMID: 30774750 DOI: 10.1155/2019/9141343
    Human skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50 μg/mL TRF treatment after SIPS induction). The differential gene expressions were assessed using microarray, GSEA, and KEGG pathway analysis. Results showed that TRF treatment significantly regulated the gene expressions, i.e., p53 (RRM2B, SESN1), ErbB (EREG, SHC1, and SHC3), and FoxO (MSTN, SMAD3) signalling pathways in the SIPS myoblasts compared to the SIPS control group (p < 0.05). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways.
  7. Fulltext The Differences in the Levels of Oxidative Status Marker and Soluble CD95 in Patients with Moderate to Severe COPD during an Exacerbation and a Stable Period
    Soodaeva S, Kubysheva N, Klimanov I, Shutov A, Eliseeva T, Novikov V, et al.
    Oxid Med Cell Longev, 2021;2021:2105406.
    PMID: 34925689 DOI: 10.1155/2021/2105406
    Studying the features of changes in markers of oxidative stress (OS) and inflammation indicators in COPD patients depending on the degree of bronchial obstruction is one of the priority directions for improving the prognosis and monitoring of the course of this pathology. We conducted a comparative investigation of changes in markers of OS and apoptosis at the systemic and local levels in patients with moderate to severe COPD during exacerbation and stable phase. 105 patients with COPD aged 46-67 and 21 healthy nonsmoking volunteers comparable in age were examined. COPD patients were divided into four groups: moderate COPD (GOLDII) during the exacerbation (GOLDIIex, n = 25) and in the stable phase (GOLDIIst, n = 27), severe COPD (GOLDIII) during the exacerbation (GOLDIIIex, n = 29), and in the stable phase (GOLDIIIst, n = 24). We studied the levels of such lipid peroxidation (LPO) products as diene conjugates (DC) and Schiff bases (SB) and parameters of induced chemiluminescence (Imax, total light sum-S, Imax/S) in blood serum, as well as sCD95 concentration in blood and exhaled breath condensate (EBC). The relationship between the values of the OS system indicators with sCD95, as well as with the parameters of lung function, was investigated. Multidirectional changes in OS indicator levels in COPD patients depending on the severity of obstructive airway disorders have been established. The maximum values of DC (0.26 ± 0.046 RU), Imax (0.265 ± 0.19 RLU), and Imax/S (0.13 ± 0.05) were typical for patients with moderate COPD, while the highest SB level (5.7 ± 2.3 RU) was observed in severe COPD during an exacerbation. The exacerbation of the disease was characterized by an increase in DC concentration in both GOLDIIex (0.26 ± 0.046 RU) and GOLDIIIex (0.209 ± 0.02 RU) compared to the stable moderate and severe COPD (0.202 ± 0.028 RU and 0.19 ± 0.03 RU, respectively, p < 0.05). The established decrease in high values of DC, Imax, Imax/S, and sCD95 and an increase in SB concentration in GOLD III can serve as quantitative indicators of the prognosis of the severity of the disease. The serum concentration of sCD95 in GOLDIIex (366.4 ± 70.5 U/ml) and GOLDIIst (361.4 ± 72.8 U/ml) did not differ from the control group (393.7 ± 80.9 U/ml, p > 0.05). In patients with FEV1 < 49% during the exacerbation and stable phase, the serum levels of Imax/S (0.058 ± 0.01 and 0.062 ± 0.01) and sCD95 (318.2 ± 66.3 U/ml and 321.4 ± 42.5 U/ml) were lower than the values of healthy volunteers (0.08 ± 0.01 and 393.7 ± 80.9 U/ml, respectively, p < 0.05). A positive correlation between sCD95 concentration and airway obstruction degree in all examined COPD patients was established. The revealed numerous associations between sCD95 and OS marker levels in GOLDIII indicate a relationship between systemic radical stress and apoptosis processes both in the respiratory tract and the whole body under conditions of severe inflammation. The established correlations between the values of DC, Imax, and sCD95 in the blood serum and the lung function parameters in all studied patients allow us to consider these indicators as additional prognostic indicators of disease intensification. Our work results help clarify the participation and detail of FRO and apoptosis processes in developing pathophysiological features in moderate to severe COPD in different periods and, accordingly, improve the efficiency of diagnosis and treatment of the disease.
  8. The Attenuation of Chronic Ulcerative Colitis by (R)-salbutamol in Repeated DSS-Induced Mice
    Deng L, Guo H, Wang S, Liu X, Lin Y, Zhang R, et al.
    Oxid Med Cell Longev, 2022;2022:9318721.
    PMID: 35178163 DOI: 10.1155/2022/9318721
    Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.
  9. Fulltext The Antioxidative Role of Natural Compounds from a Green Coconut Mesocarp Undeniably Contributes to Control Diabetic Complications as Evidenced by the Associated Genes and Biochemical Indexes
    Das RR, Rahman MA, Al-Araby SQ, Islam MS, Rashid MM, Babteen NA, et al.
    Oxid Med Cell Longev, 2021;2021:9711176.
    PMID: 34367469 DOI: 10.1155/2021/9711176
    The purpose of this study was to look into the effects of green coconut mesocarp juice extract (CMJE) on diabetes-related problems in streptozotocin- (STZ-) induced type 2 diabetes, as well as the antioxidative functions of its natural compounds in regulating the associated genes and biochemical markers. CMJE's antioxidative properties were evaluated by the standard antioxidant assays of 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide radical, nitric oxide, and ferrous ions along with the total phenolic and flavonoids content. The α-amylase inhibitory effect was measured by an established method. The antidiabetic effect of CMJE was assayed by fructose-fed STZ-induced diabetic models in albino rats. The obtained results were verified by bioinformatics-based network pharmacological tools: STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba bioinformatics tools. The results showed that GC-MS-characterized compounds from CMJE displayed a very promising antioxidative potential. In an animal model study, CMJE significantly (P < 0.05) decreased blood glucose, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, uric acid, and lipid levels and increased glucose tolerance as well as glucose homeostasis (HOMA-IR and HOMA-b scores). The animal's body weights and relative organ weights were found to be partially restored. Tissue architectures of the pancreas and the kidney were remarkably improved by low doses of CMJE. Compound-protein interactions showed that thymine, catechol, and 5-hydroxymethylfurfural of CMJE interacted with 84 target proteins. Of the top 15 proteins found by Cytoscape 3.6.1, 8, CAT and OGG1 (downregulated) and CASP3, COMT, CYP1B1, DPYD, NQO1, and PTGS1 (upregulated), were dysregulated in diabetes-related kidney disease. The data demonstrate the highly prospective use of CMJE in the regulation of tubulointerstitial tissues of patients with diabetic nephropathy.
  10. Fulltext Targeted Diagnosis, Therapeutic Monitoring, and Assessment of Atherosclerosis Based on Mesoporous Silica Nanoparticles Coated with cRGD-Platelets
    Zhang W, Lv Z, Zhang Y, Gopinath SCB, Yuan Y, Huang D, et al.
    Oxid Med Cell Longev, 2022;2022:6006601.
    PMID: 36211824 DOI: 10.1155/2022/6006601
    OBJECTIVE: The off-target effects and severe side effects of PPARα and LXRα agonists greatly limit their application in atherosclerosis (AS). Therefore, this study intended to use mesoporous silica nanoparticles as carriers to generate MnO nanoparticles in situ with T1WI-MRI in mesoporous pores and simultaneously load PPARα and LXRα agonists. Afterward, cRGD-chelated platelet membranes can be used for coating to construct a new nanotheranostic agent.

    METHODS: cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified.

    RESULTS: cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1.

    CONCLUSION: In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.

  11. Fulltext Senescence-related changes in gene expression of peripheral blood mononuclear cells from octo/nonagenarians compared to their offspring
    Abdul Rahman A, Abdul Karim N, Abdul Hamid NA, Harun R, Ngah WZ
    Oxid Med Cell Longev, 2013;2013:189129.
    PMID: 24381713 DOI: 10.1155/2013/189129
    Mechanisms determining both functional rate of decline and the time of onset in aging remain elusive. Studies of the aging process especially those involving the comparison of long-lived individuals and young controls are fairly limited. Therefore, this research aims to determine the differential gene expression profile in related individuals from villages in Pahang, Malaysia. Genome-wide microarray analysis of 18 samples of peripheral blood mononuclear cells (PBMCs) from two groups: octo/nonagenarians (80-99 years old) and their offspring (50.2 ± 4.0 years old) revealed that 477 transcripts were age-induced and 335 transcripts were age-repressed with fold changes ≥1.2 in octo/nonagenarians compared to offspring. Interestingly, changes in gene expression were associated with increased capacity for apoptosis (BAK1), cell cycle regulation (CDKN1B), metabolic process (LRPAP1), insulin action (IGF2R), and increased immune and inflammatory response (IL27RA), whereas response to stress (HSPA8), damage stimulus (XRCC6), and chromatin remodelling (TINF2) pathways were downregulated in octo/nonagenarians. These results suggested that systemic telomere maintenance, metabolism, cell signalling, and redox regulation may be important for individuals to maintain their healthy state with advancing age and that these processes play an important role in the determination of the healthy life-span.
  12. Fulltext Semipurified Ethyl Acetate Partition of Methanolic Extract of Melastoma malabathricum Leaves Exerts Gastroprotective Activity Partly via Its Antioxidant-Antisecretory-Anti-Inflammatory Action and Synergistic Action of Several Flavonoid-Based Compounds
    Ismail Suhaimy NW, Noor Azmi AK, Mohtarrudin N, Omar MH, Tohid SF, Cheema MS, et al.
    Oxid Med Cell Longev, 2017;2017:6542631.
    PMID: 28168011 DOI: 10.1155/2017/6542631
    Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition. EAMM significantly (i) reduced the volume and acidity (free and total) while increasing the pH of gastric juice and enhanced the gastric wall mucus secretion when assessed using the pylorus ligation assay, (ii) increased the enzymatic and nonenzymatic antioxidant activity of the stomach tissue, (iii) lost its gastroprotective activity following pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker), (iv) exerted antioxidant activity against various in vitro oxidation assays, and (v) showed moderate in vitro anti-inflammatory activity via the LOX-modulated pathway. In conclusion, EAMM exerts a remarkable NO/NP-SH-dependent gastroprotective effect that is attributed to its antisecretory and antioxidant activities, ability to stimulate the gastric mucus production and endogenous antioxidant system, and synergistic action of several gastroprotective-induced flavonoids.
  13. Fulltext Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation
    Ramachandran S, Verma AK, Dev K, Goyal Y, Bhatt D, Alsahli MA, et al.
    Oxid Med Cell Longev, 2021;2021:5563746.
    PMID: 34336101 DOI: 10.1155/2021/5563746
    With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.
  14. Role of Antioxidants and Natural Products in Inflammation
    Arulselvan P, Fard MT, Tan WS, Gothai S, Fakurazi S, Norhaizan ME, et al.
    Oxid Med Cell Longev, 2016;2016:5276130.
    PMID: 27803762
    Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases.
  15. Fulltext Reversal of myoblast aging by tocotrienol rich fraction posttreatment
    Lim JJ, Ngah WZ, Mouly V, Abdul Karim N
    Oxid Med Cell Longev, 2013;2013:978101.
    PMID: 24349615 DOI: 10.1155/2013/978101
    Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associated β-galactosidase (SA-β-galactosidase), and cell proliferation were determined. 50 μg/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA-β-galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA-β-galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA-β-galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed.
  16. Fulltext Redox Control of Antioxidant and Antihepatotoxic Activities of Cassia surattensis Seed Extract against Paracetamol Intoxication in Mice: In Vitro and In Vivo Studies of Herbal Green Antioxidant
    Uthaya Kumar US, Chen Y, Kanwar JR, Sasidharan S
    Oxid Med Cell Longev, 2016;2016:6841348.
    PMID: 28053693 DOI: 10.1155/2016/6841348
    The therapeutic potential of Cassia surattensis in reducing free radical-induced oxidative stress and inflammation particularly in hepatic diseases was evaluated in this study. The polyphenol rich C. surattensis seed extract showed good in vitro antioxidant. C. surattensis seed extract contained total phenolic content of 100.99 mg GAE/g dry weight and there was a positive correlation (r > 0.9) between total phenolic content and the antioxidant activities of the seed extract. C. surattensis seed extract significantly (p < 0.05) reduced the elevated levels of serum liver enzymes (ALT, AST, and ALP) and relative liver weight in paracetamol-induced liver hepatotoxicity in mice. Moreover, the extract significantly (p < 0.05) enhanced the antioxidant enzymes and glutathione (GSH) contents in the liver tissues, which led to decrease of malondialdehyde (MDA) level. The histopathological examination showed the liver protective effect of C. surattensis seed extract against paracetamol-induced histoarchitectural alterations by maximum recovery in the histoarchitecture of the liver tissue. Furthermore, histopathological observations correspondingly supported the biochemical assay outcome, that is, the significant reduction in elevated levels of serum liver enzymes. In conclusion, C. surattensis seed extract enhanced the in vivo antioxidant status and showed antihepatotoxic activities, which is probably due to the presence of phenolic compounds.
  17. Fulltext Protective effects of gelam honey against oxidative damage in young and aged rats
    Sahhugi Z, Hasenan SM, Jubri Z
    Oxid Med Cell Longev, 2014;2014:673628.
    PMID: 25505937 DOI: 10.1155/2014/673628
    Aging is characterized by progressive decline in physiological and body function due to increase in oxidative damage. Gelam honey has been accounted to have high phenolic and nonphenolic content to attenuate oxidative damage. This study was to determine the effect of local gelam honey on oxidative damage of aged rats. Twenty-four male Spraque-Dawley rats were divided into young (2 months) and aged (19 months) groups. Each group was further divided into control (fed with plain water) and supplemented with 2.5 mg/kg body weight of gelam honey for 8 months. DNA damage level was determined by comet assay and plasma malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The activity of blood and cardiac antioxidant enzymes was determined by spectrophotometer. The DNA damage and MDA level were reduced in both gelam honey supplemented groups. Gelam honey increases erythrocytes CAT and cardiac SOD activities in young and cardiac CAT activity in young and aged groups. The DNA damage was increased in the aged group compared to young group, but reduced at the end of the study. The decline of oxidative damage in rats supplemented with gelam honey might be through the modulation of antioxidant enzyme activities.
  18. Fulltext Protective effect of pulp oil extracted from Canarium odontophyllum Miq. Fruit on blood lipids, lipid peroxidation, and antioxidant status in healthy rabbits
    Shakirin FH, Azlan A, Ismail A, Amom Z, Yuon LC
    Oxid Med Cell Longev, 2012;2012:840973.
    PMID: 22685623 DOI: 10.1155/2012/840973
    The aim of this paper was to compare the effects of pulp and kernel oils of Canarium odontophyllum Miq. (CO) on lipid profile, lipid peroxidation, and oxidative stress of healthy rabbits. The oils are rich in SFAs and MUFAs (mainly palmitic and oleic acids). The pulp oil is rich in polyphenols. Male New Zealand white (NZW) rabbits were fed for 4 weeks on a normal diet containing pulp (NP) or kernel oil (NK) of CO while corn oil was used as control (NC). Total cholesterol (TC), HDL-C, LDL-c and triglycerides (TG) levels were measured in this paper. Antioxidant enzymes (superoxide dismutase and glutathione peroxidise), thiobarbiturate reactive substances (TBARSs), and plasma total antioxidant status (TAS) were also evaluated. Supplementation of CO pulp oil resulted in favorable changes in blood lipid and lipid peroxidation (increased HDL-C, reduced LDL-C, TG, TBARS levels) with enhancement of SOD, GPx, and plasma TAS levels. Meanwhile, supplementation of kernel oil caused lowering of plasma TC and LDL-C as well as enhancement of SOD and TAS levels. These changes showed that oils of CO could be beneficial in improving lipid profile and antioxidant status as when using part of normal diet. The oils can be used as alternative to present vegetable oil.
  19. Fulltext Protective effect of Momordica charantia fruit extract on hyperglycaemia-induced cardiac fibrosis
    Abas R, Othman F, Thent ZC
    Oxid Med Cell Longev, 2014;2014:429060.
    PMID: 25371774 DOI: 10.1155/2014/429060
    In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect of Momordica charantia (MC) fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ induction, the rats were subdivided (n = 6) into control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC), and diabetic group treated with 150 mg/kg of metformin (DM-Met). Administration of MC fruit extract (1.5 g/kg body weight) in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase (CAT) was observed following MC treatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded that MC fruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis.
  20. Fulltext Protective Mechanisms of Flavonoids in Parkinson's Disease
    Magalingam KB, Radhakrishnan AK, Haleagrahara N
    Oxid Med Cell Longev, 2015;2015:314560.
    PMID: 26576219 DOI: 10.1155/2015/314560
    Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage. Within the past decades, an explosion of research discoveries has reported on the protective mechanisms of flavonoids, which are plant-based polyphenols, in the treatment of neurodegenerative disease using both in vitro and in vivo models. In this paper, we have reviewed the literature on the neuroprotective mechanisms of flavonoids in protecting the dopaminergic neurons hence reducing the symptoms of this movement disorder. The mechanism reviewed includes effect of flavonoids in activation of endogenous antioxidant enzymes, suppressing the lipid peroxidation, inhibition of inflammatory mediators, flavonoids as a mitochondrial target therapy, and modulation of gene expression in neuronal cells.
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