Displaying publications 21 - 40 of 106 in total

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  1. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 32496996 DOI: 10.2174/1871530320666200604160614
    Osteoporosis is one of the major health issues associated with menopause-related estrogen deficiency. Various reports suggest that the hormonal changes related to menopausal transition may lead to the derangement of redox homeostasis and ultimately oxidative stress. Estrogen deficiency and oxidative stress may enhance the expression of genes involved in inflammation. All these factors may contribute, in synergy, to the development of postmenopausal osteoporosis. Previous studies suggest that estrogen may act as an antioxidant to protect the bone against oxidative stress, and as an antiinflammatory agent in suppressing pro-inflammatory and pro-osteoclastic cytokines. Thus, the focus of the current review is to examine the relationship between estrogen deficiency, oxidative stress and inflammation, and the impacts of these phenomena on skeletal health in postmenopausal women.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  2. Leong XF, Ng CY, Badiah B, Das S
    ScientificWorldJournal, 2014;2014:768237.
    PMID: 24526921 DOI: 10.1155/2014/768237
    This review is to examine the current literatures on the relationship between periodontitis and hypertension as well as to explore the possible biological pathways underlying the linkage between these health conditions. Hypertension is one of the major risk factors for cardiovascular diseases. Oxidative stress and endothelial dysfunction are among the critical components in the development of hypertension. Inflammation has received much attention recently and may contribute to a pivotal role in hypertension. Periodontitis, a chronic low-grade inflammation of gingival tissue, has been linked to endothelial dysfunction, with blood pressure elevation and increased mortality risk in hypertensive patients. Inflammatory biomarkers are increased in hypertensive patients with periodontitis. Over the years, various researches have been performed to evaluate the involvement of periodontitis in the initiation and progression of hypertension. Many cross-sectional studies documented an association between hypertension and periodontitis. However, more well-designed prospective population trials need to be carried out to ascertain the role of periodontitis in hypertension.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  3. Singh JC, Kakalij RM, Kshirsagar RP, Kumar BH, Komakula SS, Diwan PV
    Pharm Biol, 2015 May;53(5):630-6.
    PMID: 25472801 DOI: 10.3109/13880209.2014.935866
    Vanillic acid (VA), a flavoring agent used in food and drug products, obtained naturally from the plant Angelica sinensis (Oliv.) Diels (Apiaceae), used in the traditional Chinese medicine. It is reported to possess strong antioxidant, anti-inflammatory, and neuroprotective effects. However, the pharmacological effects on oxidative stress-induced neurodegeneration are not well investigated.
    Matched MeSH terms: Inflammation Mediators/antagonists & inhibitors; Inflammation Mediators/metabolism
  4. Gautam RK, Gupta G, Sharma S, Hatware K, Patil K, Sharma K, et al.
    Int J Rheum Dis, 2019 Jul;22(7):1247-1254.
    PMID: 31155849 DOI: 10.1111/1756-185X.13602
    AIM: The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum.

    METHOD: Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated.

    RESULTS: Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P 

    Matched MeSH terms: Inflammation Mediators/blood
  5. Kotyla PJ, Islam MA, Engelmann M
    Int J Mol Sci, 2020 Oct 07;21(19).
    PMID: 33036382 DOI: 10.3390/ijms21197390
    Janus kinase (JAK) inhibitors, a novel class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), have shown their safety and efficacy in rheumatoid arthritis (RA) and are being intensively tested in other autoimmune and inflammatory disorders. Targeting several cytokines with a single small compound leads to blocking the physiological response of hundreds of genes, thereby providing the background to stabilize the immune response. Unfortunately, blocking many cytokines with a single drug may also bring some negative consequences. In this review, we focused on the activity of JAK inhibitors in the cardiovascular system of patients with RA. Special emphasis was put on the modification of heart performance, progression of atherosclerosis, lipid profile disturbance, and risk of thromboembolic complications. We also discussed potential pathophysiological mechanisms that may be responsible for such JAK inhibitor-associated side effects.
    Matched MeSH terms: Inflammation Mediators/metabolism
  6. Ose J, Schock H, Tjønneland A, Hansen L, Overvad K, Dossus L, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Jun;24(6):951-61.
    PMID: 25855626 DOI: 10.1158/1055-9965.EPI-14-1279-T
    BACKGROUND: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse.

    METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.

    RESULTS: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity ≤ 0.01].

    CONCLUSIONS: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity.

    IMPACT: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.

    Matched MeSH terms: Inflammation Mediators/blood*
  7. Passmore MR, Byrne L, Obonyo NG, See Hoe LE, Boon AC, Diab SD, et al.
    Respir Res, 2018 Nov 22;19(1):231.
    PMID: 30466423 DOI: 10.1186/s12931-018-0935-4
    BACKGROUND: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.

    METHODS: Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases.

    RESULTS: Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β were elevated.

    CONCLUSIONS: This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.

    Matched MeSH terms: Inflammation Mediators/metabolism*
  8. Gupta S, Mishra KP, Kumar B, Singh SB, Ganju L
    J Ethnopharmacol, 2020 Oct 28;261:113022.
    PMID: 32569719 DOI: 10.1016/j.jep.2020.113022
    ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AIM: The study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis.

    MATERIALS AND METHODS: The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days.

    RESULTS: The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1β and IL-6 involved in arthritis.

    CONCLUSION: The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.

    Matched MeSH terms: Inflammation Mediators/antagonists & inhibitors*; Inflammation Mediators/metabolism
  9. Zahedi FD, Asmi NH, Husain S, Gendeh BS
    Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1837-1842.
    PMID: 31763256 DOI: 10.1007/s12070-017-1219-x
    Nasal irrigation is an effective and cheap method in managing post sinonasal surgery patients. It works by improving ciliary clearance and performing mechanical debridement of the thick crust, decreasing mucosal edema and reducing the inflammatory mediators. Presence of nasal irrigation bottle contamination and its effect on patients have been studied. The aim of this study is to prospectively identify the risk of contamination in the nasal irrigation bottle, fluid from the bottle and to correlate with endoscopic findings from the patients who had underwent sinonasal surgery. Swabs will be taken from the nasal irrigation bottle and patient's middle meatus before the surgery and at each post surgery visits (2 and 4 weeks). Patients will be advised to irrigate their nose three times per day post sinonasal surgery. During endoscopic examination of the patient's nasal cavity at 2 and 4 weeks, any evidence of infection will be noted and documented. Additionally, a swab of fluid irrigated from the nasal cavity collected during the clinic follow-ups will also be taken. The specimens will be sent to the Microbiology laboratory for standard culture and sensitivity test. A total of 27 patients completed the study and were divided into case (n = 15) and control (n = 12) groups. The CFU (colony-forming unit) value of the bacteria cultured from the nasal cavity and the nasal irrigation bottle was statistically significantly (P = 0.00) increased from the baseline to the second week follow-up in both groups but not from the second week to the fourth week follow-up. The majority of the swabs from the nasal cavity of the patients and the nasal irrigation bottles were positively cultured for Pseudomonas sp. group. Other groups of bacteria that were cultured were Enterobacter sp., Coagulase Negative Staphylococcus (CONS) and Klebsiella sp. Endoscopically, there was no clinical evidence of infection found in the nasal cavity of the patients. The nasal irrigation bottle that was used in the post sinonasal surgery treatment and for alleviation of symptoms of sinonasal diseases was found to have bacterial contamination from the swabs taken from the bottle. However, despite this finding there was not clinical evidence of infection noted from the nasal endoscopic examination. A simple and effective method of cleaning the bottle would be helpful to reduce the bacterial contamination for this useful treatment method.
    Matched MeSH terms: Inflammation Mediators
  10. Taha H, Arya A, Paydar M, Looi CY, Wong WF, Vasudeva Murthy CR, et al.
    Food Chem Toxicol, 2014 Apr;66:295-306.
    PMID: 24518542 DOI: 10.1016/j.fct.2014.01.054
    The current study aimed to ascertain the antidiabetic potential of Pseuduvaria monticola bark methanolic extract (PMm) using in vitro mechanistic study models. In particular, the study determined the effect of PMm on cellular viability, 2-NBDG glucose uptake, insulin secretion, and NF-κB translocation in mouse pancreatic insulinoma cells (NIT-1). Furthermore, in vivo acute toxicity and antidiabetic studies were performed using streptozotocin (STZ)-induced type 1 and STZ-nicotinamide-induced type 2 diabetic rat models to evaluate various biochemical parameters and markers of oxidative stress and pro-inflammatory cytokines. Five isoquinoline alkaloids and three phenolic compounds were tentatively identified in the PMm by LC/MS Triple TOF. The study results showed that PMm is non-toxic to NIT-1 cells and significantly increased the glucose uptake and insulin secretion without affecting the translocation of NF-κB. Moreover, the non-toxic effects of PMm were confirmed through an in vivo acute toxicity study, which revealed that the serum insulin and C-peptide levels were significantly upregulated in type 2 diabetic rats and that no significant changes were observed in type 1 diabetic rats. Similarly, PMm was found to downregulate the levels of oxidative stress and pro-inflammatory cytokines in type 2 diabetic rats by alleviating hyperglycemia. Therefore, we conclude that PMm may be developed as an antidiabetic agent for the treatment of type 2 diabetes-associated conditions.
    Matched MeSH terms: Inflammation Mediators/metabolism
  11. Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.
    Mucosal Immunol, 2016 Jul;9(4):859-72.
    PMID: 26555706 DOI: 10.1038/mi.2015.111
    Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
    Matched MeSH terms: Inflammation Mediators/metabolism
  12. Haque MA, Jantan I, Harikrishnan H
    Int Immunopharmacol, 2018 Feb;55:312-322.
    PMID: 29310107 DOI: 10.1016/j.intimp.2018.01.001
    Zerumbone (ZER), isolated mainly from the Zingiber zerumbet (Z. zerumbet) rhizomes was found to be effective against numerous inflammatory and immune disorders, however, the molecular and biochemical mechanisms underlying its anti-inflammatory and immunosuppressive properties have not been well studied. This study was carried out to examine the profound effects of ZER on inflammatory mediated MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways in LPS-stimulated U937 human macrophages. ZER significantly suppressed the up-regulation pro-inflammatory mediators, TNF-α, IL-1β, PGE2, and COX-2 protein in LPS-induced human macrophages. Moreover, ZER significantly downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β as well as restored the degradation of IκBα. ZER correspondingly showed remarkable attenuation of the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a concentration-dependent manner. ZER also diminished the expression of upstream signaling molecules TLR4 and MyD88, which are prerequisite for the NF-κB, MAPK and PI3K-Akt activation. Additionally, quantification of relative gene expression of TNF-α, IL-1β, and COX-2 indicated that, at a higher dose (50μM), ZER significantly downregulated the elevated mRNA transcription levels of the stated pro-inflammatory markers in LPS-stimulated U937 macrophages. The strong suppressive effects of ZER on the activation of inflammatory markers in the macrophages via MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways suggest that ZER can be a preventive and potent therapeutic candidate for the management of various inflammatory-mediated immune disorders.
    Matched MeSH terms: Inflammation Mediators/metabolism
  13. Zainal Z, Longman AJ, Hurst S, Duggan K, Hughes CE, Caterson B, et al.
    Lipids, 2009 Jul;44(7):581-92.
    PMID: 19449050 DOI: 10.1007/s11745-009-3304-8
    Palm oil is one of the most important edible oils in the world. Its composition (rich in palmitate and oleate) make it suitable for general food uses but its utility could be increased if its fatty acid quality could be varied. In this study, we have modified a palm olein fraction by transesterification with the n-3 polyunsaturated fatty acids, alpha-linolenate or eicosapentaenoic acid (EPA). Evaluation of the potential nutritional efficacy of the oils was made using chondrocyte culture systems which can be used to mimic many of the degenerative and inflammatory pathways involved in arthritis. On stimulation of such cultures with interleukin-1alpha, they showed increased expression of cyclooxygenase-2, the inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-1alpha and IL-1beta and the proteinase ADAMTS-4. This increased expression was not affected by challenge of the cultures with palm olein alone but showed concentration-dependent reduction by the modified oil in a manner similar to EPA. These results show clearly that it is possible to modify palm oil conveniently to produce a nutraceutical with effective anti-inflammatory properties.
    Matched MeSH terms: Inflammation Mediators/metabolism
  14. Hassan J, Cader RA, Kong NC, Mohd M, Rahman AR, Hod R
    EXCLI J, 2013;12:681-92.
    PMID: 26600735
    To compare the efficacy of Coupled Plasma Filtration and Adsorption (CPFA) plus Continuous Veno-Venous Haemofiltration (CVVH) versus CVVH alone as an adjunct treatment of sepsis in terms of haemodynamic stability, inotropic requirement and inflammatory mediators.
    Matched MeSH terms: Inflammation Mediators
  15. Gnanaraj C, Shah MD, Makki JS, Iqbal M
    Pharm Biol, 2016 Aug;54(8):1420-33.
    PMID: 26810847 DOI: 10.3109/13880209.2015.1104697
    Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 ± 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  16. Gnanaraj C, Shah MD, Song TT, Iqbal M
    Biomed Pharmacother, 2017 Aug;92:1010-1022.
    PMID: 28609838 DOI: 10.1016/j.biopha.2017.06.014
    Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.
    Matched MeSH terms: Inflammation Mediators/metabolism
  17. Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al.
    Eur J Pharmacol, 2011 Feb 10;652(1-3):136-44.
    PMID: 21114991 DOI: 10.1016/j.ejphar.2010.10.092
    We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  18. Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA
    Mediators Inflamm, 2021;2021:9725903.
    PMID: 33883974 DOI: 10.1155/2021/9725903
    2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.
    Matched MeSH terms: Inflammation Mediators
  19. Sim TY, Harith HH, Tham CL, Md Hashim NF, Shaari K, Sulaiman MR, et al.
    Molecules, 2018 Jun 05;23(6).
    PMID: 29874809 DOI: 10.3390/molecules23061355
    Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone analogue with therapeutic potential in asthma. Its therapeutic potential in ALI is presently unknown. Herein, the effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. The anti-inflammatory properties of tHGA were assessed by monocyte adhesion assay and analysis of MCP-1 and ICAM-1 expression. The epithelial barrier function was assessed by paracellular permeability and transepithelial electrical resistance (TEER) assays, and analysis of junctional complex molecules expression. To elucidate the mechanism of action, the effects of tHGA on the NF-κB and MAPK pathways were determined. Gene and protein expression were analyzed by RT-PCR and Western blotting or ELISA, respectively. tHGA suppressed leukocyte adhesion to TNF-α-induced epithelium and reduced MCP-1 and ICAM-1 gene expression and secretion. tHGA also increased TEER readings, reduced epithelial permeability and enhanced expression of junctional complex molecules (zona occludens-1, occludin and E-cadherin) in TNF-α-induced cells. Correspondingly, the NF-κB, ERK and p38 MAPK pathways were also inhibited by tHGA. These findings suggest that tHGA is able to preserve alveolar epithelial barrier function in response to acute inflammation, via its anti-inflammatory activity and stabilization of epithelial barrier integrity, mediated by NF-κB, ERK and p38 MAPK signaling.
    Matched MeSH terms: Inflammation Mediators/pharmacology*
  20. Das S, Hamsi MA, Kamisah Y, Qodriyah HMS, Othman F, Emran A, et al.
    Pak J Pharm Sci, 2017 Sep;30(5):1609-1615.
    PMID: 29084680
    Consumption of corn oil for cooking purpose is gaining popularity. The present study examined the effect of heated corn oil on blood pressure and its possible mechanism in experimental rats. Thirty male Sprague-Dawley rats were randomly divided into 5 groups and were fed with the following diets, Group I was fed with basal diet only; whereas group II,III,IV and V were fed with basal diet fortified with 15% (w/w) either fresh, once-heated, five-times-heated or ten-times-heated corn oil, respectively for 16 weeks. Body weight, blood pressure were measured at baseline and weekly interval for 16 weeks. Inflammatory biomarkers which included soluble intracellular adhesion molecules (sICAM), soluble vascular adhesion molecules (sVCAM) and C reactive protein (CRP), were measured at baseline and the end of 16 weeks. The rats were sacrificed and thoracic aorta was taken for measurement of vascular reactivity. There was significant increase in the blood pressure in the groups fed with heated once, five-times (5HCO) and ten-times-heated corn oil (10-HCO) compared to the control. The increase in the blood pressure was associated with an increase in CRP, sICAM and sVCAM, reduction in vasodilatation response to acetylcholine and greater vasoconstriction response to phenylephrine. The results suggest that repeatedly heated corn oil causes elevation in blood pressure, vascular inflammation which impairs vascular reactivity thereby predisposing to hypertension. There is a need to educate people not to consume corn oil in a heated state.
    Matched MeSH terms: Inflammation Mediators/blood*
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