Displaying publications 1 - 20 of 271 in total

Abstract:
Sort:
  1. Abd Rashid N, Hussan F, Hamid A, Adib Ridzuan NR, Halim SASA, Abdul Jalil NA, et al.
    EXCLI J, 2020;19:1246-1265.
    PMID: 33122975 DOI: 10.17179/excli2020-2355
    Oxidative stress, inflammation and apoptosis are thought as primary mediators of cisplatin-induced hepatotoxicity. The objective of this study was to determine the protective effect of Polygonum minus essential oil in cisplatin-induced hepatotoxicity. A total of forty-two male rats were randomly divided into seven groups: control, cisplatin, β-caryophyllene 150 mg/kg (BCP), PmEO 100 mg/kg + cisplatin (PmEO100CP), PmEO 200 mg/kg + cisplatin (PmEO200CP), PmEO 400 mg/kg + cisplatin (PmEO400CP) and PmEO 400 mg/kg (PmEO400). Rats in the BCP, PmEO100CP, PmEO200CP, PmEO400CP and PmEO400 group received respective treatment orally for 14 consecutive days prior to cisplatin injection. All animals except for those in the control group and PmEO400 were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally on day 15 and all animals were sacrificed on day 18. PmEO100CP pretreatment protected against cisplatin-induced hepatotoxicity by decreasing CYP2E1 and indicators of oxidative stress including malondialdehyde, 8-OHdG and protein carbonyl which was accompanied by increased antioxidant status (glutathione, glutathione peroxidase, superoxide dismutase and catalase) as compared to cisplatin group. PmEO100CP pretreatment also modulated changes in liver inflammatory markers (TNF-α, IL-1α, IL-1β, IL-6 and IL-10). PmEO100CP administration also notably reduced cisplatin-induced apoptosis significantly as compared to cisplatin group. In conclusion, our results suggested that P. minus essential oil at a dose of 100 mg/kg may protect against cisplatin-induced hepatotoxicity possibly via inhibition of oxidative stress, inflammation and apoptosis.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  2. Abdo Qaid EY, Abdullah Z, Zakaria R, Long I
    Neurol Res, 2024 Mar;46(3):261-271.
    PMID: 38122814 DOI: 10.1080/01616412.2023.2296754
    INTRODUCTION: The neuroinflammatory response was seen to impact the formation of phosphorylated tau protein in Alzheimer's disease (AD). This study aims to investigate the molecular mechanism of minocycline in reducing phosphorylated tau protein formation in the hippocampus of lipopolysaccharide (LPS)-induced rats.

    METHODS: Fifty adult male Sprague Dawley (SD) rats were randomly allocated to 1 of 5 groups: control, LPS (5 mg/kg), LPS + minocycline (25 mg/kg), LPS + minocycline (50 mg/kg) and LPS + memantine (10 mg/kg). Minocycline and memantine were administered intraperitoneally (i.p) for two weeks, and LPS was injected i.p. once on day 5. ELISA was used to determine the level of phosphorylated tau protein in SD rats' hippocampal tissue. The density and expression of Toll-like receptor-4 (TLR-4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кβ), tumour necrosis factor-alpha (TNF-α), and cyclooxygenase (COX)-2 were determined using Western blot and immunohistochemistry.

    RESULTS: Minocycline, like memantine, prevented LPS-induced increasein phosphorylated tau protein level suggested via reduced density and expression of TLR-4, NF-кβ, TNF-αand COX-2 proteins in rat hippocampal tissue. Interestingly, higher doses were shown to be more neuroprotective than lower doses.

    CONCLUSION: This study suggests that minocycline suppresses the neuroinflammation signalling pathway and decreased phosphorylated tau protein formation induced by LPS in a dose-dependent manner. Minocycline can be used as a preventative and therapeutic drug for neuroinflammatory diseases such as AD.

    Matched MeSH terms: Tumor Necrosis Factor-alpha/metabolism
  3. Abood WN, Al-Henhena NA, Najim Abood A, Al-Obaidi MM, Ismail S, Abdulla MA, et al.
    Bosn J Basic Med Sci, 2015 05 12;15(2):25-30.
    PMID: 26042509 DOI: 10.17305/bjbms.2015.39
    The wound-healing potential of Phaleria macrocarpa was evaluated by monitoring the levels of inflammatory mediators, collagen, and antioxidant enzymes. Experimentally, two-centimeter-wide full-thickness-deep skin excision wounds were created on the posterior neck area of the rats. The wounds were topically treated with gum acacia as a vehicle in the control group, intrasite gel in the reference group, and 100 and 200 mg/mL P. macrocarpa ‎fruit extract in the treatment group. Granulation tissues were excised on the 15th day and were further processed for histological and biochemical analyzes. Wound healing was evaluated by measuring the contractions and protein contents of the wounds. Cellular redistribution and collagen deposition were assessed morphologically using Masson's trichrome stain. Superoxide dismutase (SOD) and catalase (CAT) activities, along with malondialdehyde (MDA) level were determined in skin tissue homogenates of the dermal wounds. Serum levels of transforming growth factor beta 1 (TGF-β1) and tumor necrosis factor alpha (TNF-α) were evaluated in all the animals. A significant decrease in wound area was caused by a significant increase in TGF-β1 level in the treated groups. Decrease in TNF-α level and increase in the collagen formation were also observed in the treated groups. Topical treatment with P. macrocarpa fruit extract increased the SOD and CAT activities in the healing wounds, thereby significantly increasing MDA level. The topical treatment with P. macrocarpa fruit extract showed significant healing effect on excision wounds and demonstrated an important role in the inflammation process by increasing antioxidant enzyme activities, thereby accelerating the wound healing process and reducing tissue injury.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/blood
  4. Abu Bakar MH, Hairunisa N, Zaman Huri H
    Clin Exp Med, 2018 Aug;18(3):373-382.
    PMID: 29550985 DOI: 10.1007/s10238-018-0495-4
    Altered mitochondrial DNA (mtDNA) is the most common denominator to numerous metabolic diseases. The present study sought to investigate the correlation between mtDNA content in lymphocytes and associated clinical risk factors for impaired fasting glucose (IFG). We included 23 healthy control and 42 IFG participants in this cross-sectional study. The measurements of mtDNA content in lymphocytes and pro-inflammatory markers derived from both normal and diseased individuals were quantified. Spearman partial correlation and multivariate statistical analyses were employed to evaluate the association between mtDNA content and other metabolic covariates in IFG. Reduced mtDNA content was observed in the IFG group with microvascular complications than those without complications. The IFG patients with lowest median of mtDNA content had considerably elevated hyperglycemia, insulin resistance and inflammation. The adjusted partial correlation analysis showed that mtDNA content was positively correlated with HDL-cholesterol and IL-10 (P factors. Our data show that reduced mtDNA content in lymphocytes was associated with insulin resistance and inflammation in individuals with IFG.
    Study site: Outpatient clinics, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
    Matched MeSH terms: Tumor Necrosis Factor-alpha/blood; Tumor Necrosis Factor-alpha/immunology
  5. Adamu HA, Imam MU, Der-Jiun O, Ismail M
    J Nutrigenet Nutrigenomics, 2017;10(1-2):19-31.
    PMID: 28399529 DOI: 10.1159/000469663
    BACKGROUND: Numerous studies have reported on the influence of diet on insulin resistance. Our study provides insight into the effect of germinated brown rice (GBR) and γ-aminobutyric acid (GABA) on early environment-driven programming and susceptibility to insulin resistance in rat offspring.

    METHODS: Male rat offspring from female Sprague-Dawley rats fed with a high-fat diet (HFD) alone, HFD + GBR, or HFD + GABA extract throughout pregnancy and lactation were weaned 4 weeks after delivery and followed up for 8 weeks. A biochemical analysis and an assessment of the hepatic expression of insulin signaling genes were performed.

    RESULTS: The results showed that intrauterine exposure to HFD caused metabolic perturbations in rat offspring which gravitated towards insulin resistance even though the rat offspring did not consume an HFD. GBR and GABA attenuated the HFD-induced changes by underlying regulation of the insulin signaling genes.

    CONCLUSIONS: The results suggest that intake of GBR and GABA during pregnancy and lactation can influence the programming of genes in rat offspring, thereby enhancing insulin sensitivity.

    Matched MeSH terms: Tumor Necrosis Factor-alpha/blood
  6. Agarwal R, Krasilnikova AV, Raja IS, Agarwal P, Mohd Ismail N
    Eur J Pharmacol, 2014 May 5;730:8-13.
    PMID: 24583339 DOI: 10.1016/j.ejphar.2014.02.021
    Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have similarity with those of prostaglandin analogs. The present study investigated the involvement of matrix metalloproteinases (MMPs) and cytokine activity modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor. Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering effect of ACEI. Topical treatment with single drop of enalaprilat resulted in significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h post-instillation. Treatment with losartan resulted in a peak IOP reduction of 13.3%, which was significantly lower than enalaprilat, indicating involvement of mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin II type 1 receptor stimulation and modulation of MMP and cytokines activities.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/metabolism
  7. Agarwal R, Agarwal P
    Indian J Ophthalmol, 2012 Jul;60(4):255-61.
    PMID: 22824592 DOI: 10.4103/0301-4738.98700
    Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/biosynthesis*
  8. Ahmad S, Israf DA, Lajis NH, Shaari K, Mohamed H, Wahab AA, et al.
    Eur J Pharmacol, 2006 May 24;538(1-3):188-94.
    PMID: 16650843
    Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2',4'-dihydroxy-6'-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE(2) production from lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2) via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively. Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-alpha from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8 microM and 4.6 microM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on the 4' or 6' locations of the A benzene ring.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/biosynthesis
  9. Ahmad S, Azid NA, Boer JC, Lim J, Chen X, Plebanski M, et al.
    Front Immunol, 2018;9:2572.
    PMID: 30473698 DOI: 10.3389/fimmu.2018.02572
    Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine, which is thought to play a major role in the pathogenesis of inflammatory diseases, including allergy. TNF is produced at the early stage of allergen sensitization, and then continues to promote the inflammation cascade in the effector phase of allergic reactions. Consequently, anti-TNF treatment has been proposed as a potential therapeutic option. However, recent studies reveal anti-intuitive effects of TNF in the activation and proliferative expansion of immunosuppressive Tregs, tolerogenic DCs and MDSCs. This immunosuppressive effect of TNF is mediated by TNFR2, which is preferentially expressed by immunosuppressive cells. These findings redefine the role of TNF in allergic reaction, and suggest that targeting TNF-TNFR2 interaction itself may represent a novel strategy in the treatment of allergy.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/immunology*
  10. Ahmad S, Mohd Noor N, Engku Nur Syafirah EAR, Irekeola AA, Shueb RH, Chan YY, et al.
    J Interferon Cytokine Res, 2023 Feb;43(2):77-85.
    PMID: 36795972 DOI: 10.1089/jir.2022.0211
    Tumor-necrosis factor (TNF) is recognized as a therapeutic target in inflammatory diseases, including asthma. In severe forms of asthma, biologics such as anti-TNF are rendered to be investigated as therapeutic options in severe asthma. Hence, this work is done to assess the efficacy and safety of anti-TNF as a supplementary therapy for patients with severe asthma. A systematic search of 3 databases (Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov) was performed to identify for published and unpublished randomized controlled trials comparing anti-TNF (etanercept, adalimumab, infliximab, certolizumab pegol, golimumab) with placebo in patients diagnosed with persistent or severe asthma. Random-effects model was used to estimate risk ratios and mean differences (MDs) with confidence intervals (95% CIs). PROSPERO registration number is CRD42020172006. Four trials with 489 randomized patients were included. Comparison between etanercept and placebo involved 3 trials while comparison between golimumab and placebo involved 1 trial. Etanercept produced a small but significant impairment in forced expiratory flow in 1 second (MD 0.33, 95% CI 0.09-0.57, I2 statistic = 0%, P = 0.008) and a modest improvement of asthma control using the Asthma Control Questionnaire. However, using the Asthma Quality of Life Questionnaire, the patients exhibit an impaired quality of life with etanercept. Treatment with etanercept showed a reduced injection site reaction and gastroenteritis compared with placebo. Although treatment with anti-TNF is shown to improve asthma control, severe asthma patients did not benefit from this therapy as there is limited evidence for improvement in lung function and reduction of asthma exacerbation. Hence, it is unlikely to prescribe anti-TNF in adults with severe asthma.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  11. Ahmad W, Jantan I, Kumolosasi E, Haque MA, Bukhari SNA
    Int Immunopharmacol, 2018 Jul;60:141-151.
    PMID: 29730557 DOI: 10.1016/j.intimp.2018.04.046
    The in vivo immunomodulatory activities of Tinospora crispa have been reported but its molecular mechanisms underlying its immunomodulatory properties remains obscure and the active constituents contributing to the activities have not been identified. The present study was aimed to investigate the immunomodulatory effects of T. crispa extract (TCE) and its chemical constituents on RAW 264.7 macrophages. Six known compounds including magnoflorine and syringin were isolated by various chromatographic techniques from TCE and their structures were determined spectroscopically. A validated HPLC method was used to quantify magnoflorine and syringin in the extract. The immunomodulatory effects of TCE and its isolated compounds on chemotaxis, phagocytosis, production of inflammatory mediators including reactive oxygen species (ROS), nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines which include tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) on macrophages were assessed. TCE increased the chemotaxis and phagocytic activity of macrophages and significantly enhanced the production of ROS, NO and pro-inflammatory cytokines. All alkaloids isolated, specifically magnoflorine showed remarkable inducing effects on the chemotaxis, phagocytic activity, ROS and NO productions and the secretions of IL-1β, TNF-α, IL6, PGE2 and MCP-1. In contrast, syringin potently reduced the chemotaxis, phagocytic activity, ROS and NO productions and secretions of IL-1β, TNF-α, IL6, PGE2 and MCP-1. TCE showed strong immunostimulant effects on various components of the immune system and these activities were possibly contributed mainly by the alkaloids specifically magnoflorine. TCE has potential to be developed as an effective natural immunostimulant for improvement of immune-related disorders.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  12. Ahmed S, Sulaiman SA, Othman NH
    PMID: 28479926 DOI: 10.1155/2017/5904361
    Breast cancer has been recognized as the leading cause of death in women worldwide. Research has shown the importance of complementary and alternative therapies in cancer. In this study, we investigated the antitumoural therapeutic effects of Malaysian Tualang honey (TH) and Australian/New Zealand Manuka honey (MH) against breast cancer in rats. Thirty syngeneic virgin female Sprague-Dawley (SD) rats were induced by the carcinogen 1-methyl-1-nitrosourea (MNU) 80 mg/kg. The treatment started when first palpable tumour reached 10-12 mm in size by dividing rats into following groups: Group 0 (negative control); Group 1 (positive control); and Groups 2 and 3 which received 1.0 g/kg body weight/day of TH and MH, respectively, for 120 days. The data demonstrate that cancer masses in TH and MH treated groups showed a lower median tumour size, weight, and multiplicity compared with the nontreated positive control (p < 0.05). Treatment also showed a dramatic slower growth rate (up to 70.82%) compared with the nontreated control (0%) (p < 0.05). The antitumoural effect was mediated through modulation of tumour growth, tumour grading, estrogenic activity, and haematological parameters. Our findings demonstrate that systemic administration of TH and MH increases the susceptibility of expression of proapoptotic proteins (Apaf-1, Caspase-9, IFN-γ, IFNGR1, and p53) and decreases the expression of antiapoptotic proteins (TNF-α, COX-2, and Bcl-xL 1) in its mechanism of action. This highlights a potential novel role for TH and MH in alleviating breast cancer.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  13. Ahmed S, Othman NH
    PMID: 24363771 DOI: 10.1155/2013/829070
    The main treatment for cancer is by using chemotherapy and radiotherapy which themselves are toxic to other viable cells of the body. Recently, there are many studies focusing on the use of natural products for cancer prevention and treatment. Of these natural products, honey has been extensively researched. The mechanism of the anti-cancer activity of honey as chemopreventive and therapeutic agent has not been completely understood. The possible mechanisms are due to its apoptotic, antiproliferative, antitumor necrosis factor (anti-TNF), antioxidant, anti-inflammatory, estrogenic and immunomodulatory activities. We collate the findings of several studies published in the literature in order to understand the mechanism of its action.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  14. Al-Hatamleh MAI, Ahmad S, Boer JC, Lim J, Chen X, Plebanski M, et al.
    J Oncol, 2019;2019:6313242.
    PMID: 31239840 DOI: 10.1155/2019/6313242
    In the past decade, nanomedicine research has provided us with highly useful agents (nanoparticles) delivering therapeutic drugs to target cancer cells. The present review highlights nanomedicine applications for breast cancer immunotherapy. Recent studies have suggested that tumour necrosis factor (TNF) and its receptor 2 (TNFR2) expressed on breast cancer cells have important functional consequences. This cytokine/receptor interaction is also critical for promoting highly immune-suppressive phenotypes by regulatory T cells (Tregs). This review generally provides a background for nanoparticles as potential drug delivery agents for immunomodulators and further discusses in depth the potential of TNF antagonists delivery to modulate TNF-TNFR2 interactions and inhibit breast cancer progression.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  15. Al-Qubaisi MS, Rasedee A, Flaifel MH, Eid EEM, Hussein-Al-Ali S, Alhassan FH, et al.
    Eur J Pharm Sci, 2019 May 15;133:167-182.
    PMID: 30902654 DOI: 10.1016/j.ejps.2019.03.015
    Thymoquinone is an effective phytochemical compound in the treatment of various diseases. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. In this work, we developed a novel inclusion complex of thymoquinone and hydroxypropyl-β-cyclodextrin that features improved solubility and bioactivity. The drug solubility was markedly accelerated in the increasing ratio of hydroxypropyl-β-cyclodextrin to thymoquinone amount. The formation of the thymoquinone/hydroxypropyl-β-cyclodextrin inclusion complex was evidenced using X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, Fourier transform infrared, scanning electron microscopy and nuclear magnetic resonance. The release behavior of the complex, as well as of their mixtures, was examined in artificial gastric (pH 1.2) and intestinal (pH 6.8) dissolution media. The formulated complex released the drug rapidly at the initial stage, followed by a slow release. Thermodynamic parameters ΔH, ΔS and ΔG were calculated with temperatures ranging from 20 to 45 °C to evaluate the complexation process. The activity of the inclusion complex was evaluated on IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells by monitoring key allergic mediators. The results revealed that compared with free thymoquinone, the inclusion complex more strongly inhibited the release of histamine, tumor necrosis factor-α, and interleukin-4, and was not cytotoxic at the tested thymoquinone concentrations (0.125-4 μg/mL) indicating the inclusion complex possibly had better antiallergic effects. Our finding suggested that the inclusion complex achieved prolonged action and reduced side-effect of thymoquinone.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/metabolism
  16. Alafiatayo AA, Lai KS, Ahmad S, Mahmood M, Shaharuddin NA
    Genomics, 2020 01;112(1):484-493.
    PMID: 30946891 DOI: 10.1016/j.ygeno.2019.03.011
    Exposing the skin to solar UV radiation induces cascades of signaling pathways and biological alterations such as redox imbalance, suppression of antioxidant genes and programmed cell death. Therefore, the aim of this study was to use RNA-Seq to unravel the effects of UV radiation on Normal Human Adult Fibroblast cells (NHDF). Cells were exposed to UV (20 mJ/cm2 for 3 mins) and incubated for 24 h. Total mRNA from the cells generated libraries of 72,080,648 and 40,750,939 raw reads from UV-treated and control cells respectively. Of the differentially expressed genes (DEGs) produced 2,007 were up-regulated and 2,791 were down-regulated (fold change ≥2, p 
    Matched MeSH terms: Tumor Necrosis Factor-alpha/metabolism
  17. Alagan A, Jantan I, Kumolosasi E, Ogawa S, Abdullah MA, Azmi N
    Front Pharmacol, 2019;10:632.
    PMID: 31231221 DOI: 10.3389/fphar.2019.00632
    Background:Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against functional changes remain unexplored. Therefore, we sought to examine the protective effects of 80% v/v ethanol extract of PA on lipopolysaccharide (LPS)-induced non-spatial memory impairment and neuroinflammation. Methods: Selected major phytoconstituents of PA extract were identified and quantified using high-performance liquid chromatography. Subchronic neurotoxicity was performed in male Wistar rats given daily oral administration of 100, 200, and 400 mg/kg of the PA extract. Their neurobehavioral activities (functional observation battery and locomotor activity) were scored, and the extracted brains were examined for neuropathological changes. Rats were treated orally with vehicle (5% Tween 20), PA extract (100, 200, and 400 mg/kg), or ibuprofen (IBF; 40 mg/kg) for 14 and 28 days before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly (p < 0.05) decreased the release of proteins like TNF-α, IL-1β, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin immunoreactivity were also reduced as compared with those in the LPS-challenged group. Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to identify the bioactive phytochemicals and the precise underlying mechanisms.
    Matched MeSH terms: Tumor Necrosis Factor-alpha
  18. Alawieyah Syed Mortadza S, Sim JA, Neubrand VE, Jiang LH
    Glia, 2018 03;66(3):562-575.
    PMID: 29143372 DOI: 10.1002/glia.23265
    Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD. Exposure to 10-300 nM Aβ42 induced concentration-dependent microglial activation and generation of TNF-α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2-KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42 -induced microglial activation and generation of TNF-α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase-1 (PARP-1). Aβ42 -induced generation of ROS and activation of PARP-1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42 -induced activation of PARP-1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42 -induced activation of PARP-1 was attenuated by TRPM2-KO and moreover, the remaining PARP-1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX-mediated generation of ROS and subsequent activation of PARP-1 play a role in Aβ42 -induced TRPM2 channel activation and TRPM2-dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP-1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ-induced AD-related neuroinflammation.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/metabolism*
  19. Ali AH, Sudi S, Basir R, Embi N, Sidek HM
    J Med Food, 2017 Feb;20(2):152-161.
    PMID: 28146408 DOI: 10.1089/jmf.2016.3813
    Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.
    Matched MeSH terms: Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/metabolism
  20. Ali Salim KM, Abd Jalil A, Radzi Z, Ismail SM, Czernuszka JT, Rahman MT
    Materials (Basel), 2020 Oct 06;13(19).
    PMID: 33036128 DOI: 10.3390/ma13194436
    OBJECTIVE: Reconstruction of oral and facial defects often necessitate replacement of missing soft tissue. The purpose of tissue expanders is to grow healthy supplementary tissue under a controlled force. This study investigates the inflammatory responses associated with the force generated from the use of anisotropic hydrogel tissue expanders.

    METHODS: Sprague Dawley rats (n = 7, body weight = 300 g ± 50 g) were grouped randomly into two groups-control (n = 3) and expanded (n = 4). Anisotropic hydrogel tissue expanders were inserted into the frontal maxillofacial region of the rats in the expanded group. The rats were sacrificed, and skin samples were harvested, fixed in formalin, and embedded in paraffin wax for histological investigation. Hematoxylin and eosin staining was performed to detect histological changes between the two groups and to investigate the inflammatory response in the expanded samples. Three inflammatory markers, namely interleukin (IL)-1α, IL-6, and tumor necrosis factor-α (TNF-α), were analyzed by immunohistochemistry.

    RESULT: IL-1-α expression was only observed in the expanded tissue samples compared to the controls. In contrast, there was no significant difference in IL-6, and TNF-α production. Histological analysis showed the absence of inflammatory response in expanded tissues, and a negative non-significant correlation (Spearman's correlation coefficient) between IL-1-α immune-positive cells and the inflammatory cells (r = -0.500). In conclusion, tissues that are expanded and stabilized using an anisotropic self-inflating hydrogel tissue expander might be useful for tissue replacement and engraftment as the expanded tissue does not show any sign of inflammatory responses. Detection of IL-1-α in the expanded tissues warrants further investigation for its involvement without any visible inflammatory response.

    Matched MeSH terms: Tumor Necrosis Factor-alpha
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links