Displaying publications 1 - 20 of 216 in total

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  1. Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.
    J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
    PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051
    The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
    Matched MeSH terms: Lipopolysaccharides/toxicity*
  2. Moriya S, Tan VP, Yee AK, Parhar IS
    Neurosci Lett, 2019 08 24;708:134330.
    PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330
    In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.
    Matched MeSH terms: Lipopolysaccharides/genetics; Lipopolysaccharides/pharmacology*
  3. Ooi TC, Chan KM, Sharif R
    Immunopharmacol Immunotoxicol, 2017 Oct;39(5):259-267.
    PMID: 28697633 DOI: 10.1080/08923973.2017.1344987
    CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer.

    OBJECTIVE: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages.

    MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay.

    RESULTS: Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine.

    CONCLUSION: Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

    Matched MeSH terms: Lipopolysaccharides/toxicity*
  4. Ooi TC, Chan KM, Sharif R
    Biol Trace Elem Res, 2016 Aug;172(2):458-464.
    PMID: 26749414 DOI: 10.1007/s12011-015-0615-x
    This study aimed to investigate the role of the mitogen-activated protein kinases (MAPKs) signaling pathway in the anti-inflammatory effects of zinc carnosine (ZnC) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Cells were pretreated with ZnC (0-100 μM) for 2 h prior to the addition of LPS (1 μg/ml). Following 24 h of treatment, ZnC was found not to be cytotoxic to RAW 264.7 cells up to the concentration of 100 μM. Our current findings showed that ZnC did not protect RAW 264.7 cells from LPS-induced "respiratory burst". Significant increment in intracellular glutathione (GSH) level and reduction in thiobarbituric acid reactive substances (TBARS) concentration can only be observed in cell pretreated with high doses of ZnC only (50 and 100 μM for GSH and 100 μM only for TBARS). On the other hand, pretreatment of cells with ZnC was able to inhibit LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression significantly. Furthermore, results from immunoblotting showed that ZnC was able to suppress nuclear factor-kappaB (NF-κB) activation, and highest suppression can be observed at 100 μM of ZnC pretreatment. However, pretreatment of ZnC did not inhibit the early activation of MAPKs. In conclusion, pretreatment with ZnC was able to inhibit the expression of inflammatory mediators in LPS-induced RAW 264.7 cells, mainly via suppression of NF-κB activation, and is independent of the MAPKs signaling pathway.
    Matched MeSH terms: Lipopolysaccharides/antagonists & inhibitors*; Lipopolysaccharides/pharmacology
  5. 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: Lipopolysaccharides/immunology
  6. Chia JSM, Izham NAM, Farouk AAO, Sulaiman MR, Mustafa S, Hutchinson MR, et al.
    Front Pharmacol, 2020;11:92.
    PMID: 32194397 DOI: 10.3389/fphar.2020.00092
    Zerumbone has shown great potential in various pathophysiological models of diseases, particularly in neuropathic pain conditions. Further understanding the mechanisms of action is important to develop zerumbone as a potential anti-nociceptive agent. Numerous receptors and pathways function to inhibit and modulate transmission of pain signals. Previously, we demonstrated involvement of the serotonergic system in zerumbone's anti-neuropathic effects. The present study was conducted to determine zerumbone's modulatory potential involving noradrenergic, transient receptor potential vanilloid type 1 (TRPV1) and N-methyl-D-aspartate (NMDA) receptors in chronic constriction injury (CCI)-induced in vitro and lipopolysaccharide (LPS)-induced SH-SY5Y in vitro neuroinflammatory models. von Frey filament and Hargreaves plantar tests were used to assess allodynia and hyperalgesia in the chronic constriction injury-induced neuropathic pain mouse model. Involvement of specific adrenoceptors were investigated using antagonists- prazosin (α1-adrenoceptor antagonist), idazoxan (α2-adrenoceptor antagonist), metoprolol (β1-adrenoceptor antagonist), ICI 118,551 (β2-adrenoceptor antagonist), and SR 59230 A (β3-adrenoceptor antagonist), co-administered with zerumbone (10 mg/kg). Involvement of excitatory receptors; TRPV and NMDA were conducted using antagonists capsazepine (TRPV1 antagonist) and memantine (NMDA antagonist). Western blot was conducted to investigate the effect of zerumbone on the expression of α2A-adrenoceptor, TRPV1 and NMDA NR2B receptors in CCI-induced whole brain samples of mice as well as in LPS-induced SH-SY5Y neuroblastoma cells. Pre-treatment with α1- and α2-adrenoceptor antagonists significantly attenuated both anti-allodynic and anti-hyperalgesic effects of zerumbone. For β-adrenoceptors, only β2-adrenoceptor antagonist significantly reversed the anti-allodynic and anti-hyperalgesic effects of zerumbone. β1-adrenoceptor antagonist only reversed the anti-allodynic effect of zerumbone. The anti-allodynic and anti-hyperalgesic effects of zerumbone were both absent when TRPV1 and NMDA receptors were antagonized in both nociceptive assays. Zerumbone treatment markedly decreased the expression of α2A-adrenoceptor, while an up-regulation was observed of NMDA NR2B receptors. Expression of TRPV1 receptors however did not significantly change. The in vitro study, representing a peripheral model, demonstrated the reduction of both NMDA NR2B and TRPV1 receptors while significantly increasing α2A-adrenoceptor expression in contrast to the brain samples. Our current findings suggest that the α1-, α2-, β1- and β2-adrenoceptors, TRPV1 and NMDA NR2B are essential for the anti-allodynic and antihyperalgesic effects of zerumbone. Alternatively, we demonstrated the plasticity of these receptors through their response to zerumbone's administration.
    Matched MeSH terms: Lipopolysaccharides
  7. Rahim NS, Lim SM, Mani V, Hazalin NAMN, Majeed ABA, Ramasamy K
    J Diet Suppl, 2020 Oct 14.
    PMID: 33962540 DOI: 10.1080/19390211.2020.1830223
    Neuroinflammation is associated with neuronal cell death and could lead to chronic neurodegeneration. This study investigated the neuroprotective potential of virgin coconut oil (VCO) against lipopolysaccharide (LPS)-induced cytotoxicity of neuroblastoma SK-N-SH cells. The findings were validated using Wistar rats, which were fed with 1-10 g/kg VCO for 31 days, exposed to LPS (0.25 mg/kg) and subjected to the Morris Water Maze Test. Brain homogenate was subjected to biochemical analyses and gene expression studies. α-Tocopherol (α-T; 150 mg/kg) served as the positive control. VCO (100 µg/mL) significantly (p 
    Matched MeSH terms: Lipopolysaccharides
  8. Puspitasari Y, Salleh A, Zamri-Saad M
    BMC Vet Res, 2020 Jun 09;16(1):186.
    PMID: 32517749 DOI: 10.1186/s12917-020-02415-2
    BACKGROUND: Pasteurella multocida B:2 causes haemorrhagic septicaemia in cattle and buffaloes. However, buffaloes are found to be more susceptible to the infection than cattle. Upon infection, the pathogen rapidly spread from the respiratory tract to the blood circulation within 16-72 h, causing septicaemia. So far, limited study has been conducted to evaluate the response of endothelial cells of buffalo towards P. multocida B:2 and its lipopolysaccharide (LPS). This study aimed to evaluate the ultrastructural changes in the aortic endothelium of buffaloes (BAEC) following exposure to P. multocida B:2 and its endotoxin. The endothelial cells were harvested from the aorta of healthy buffaloes and were prepared as monolayer cell cultures. The cultures were divided into 3 groups before Group 1 was inoculated with 107 cfu/ml of whole cell P. multocida B:2, Group 2 with LPS, which was extracted earlier from 107 cfu/ml of P. multocida B:2 and Group 3 with sterile cell culture medium. The cells were harvested at 0, 6, 12, 18, 24, 36, and 48 h post-inoculation for assessment of cellular changes using transmission electron microscopy.

    RESULTS: The BAEC of Groups 1 and 2 demonstrated moderate to severe endothelial lysis, suggestive of acute cellular injury. In general, severity of the ultrastructural changes increased with the time of incubation but no significant difference (p > 0.05) in the severity of the cellular changes between Groups 1 and 2 was observed in the first 18 h. The severity of lesions became significant (p 

    Matched MeSH terms: Lipopolysaccharides/toxicity
  9. Ng WL, Marinov GK, Chin YM, Lim YY, Ea CK
    Sci Rep, 2017 09 25;7(1):12227.
    PMID: 28947785 DOI: 10.1038/s41598-017-12550-w
    Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.
    Matched MeSH terms: Lipopolysaccharides/metabolism*
  10. Alwash MS, Aqma WS, Ahmad WY, Ibrahim N
    Int J Microbiol, 2020;2020:6915483.
    PMID: 32089696 DOI: 10.1155/2020/6915483
    Pseudomonas aeruginosa is one of the main causes of nosocomial infections and is frequently associated with opportunistic infections among hospitalized patients. Kaempferol-3-O-(2',6'-di-O-trans-p-coumaroyl)-β-D glucopyranoside (KF) is an antipseudomonal compound isolated from the leaves of the native medicinal plant Melastoma malabathricum. Herein, an RNA-seq transcriptomic approach was employed to study the effect of KF treatment on P. aeruginosa and to elucidate the molecular mechanisms underlying the response to KF at two time points (6 h and 24 h incubation). Quantitative real-time PCR (qRT-PCR) was performed for four genes (uvrD, sodM, fumC1, and rpsL) to assess the reliability of the RNA-seq results. The RNA-seq transcriptomic analysis revealed that KF increases the expression of genes involved in the electron transport chain (NADH-I), resulting in the induction of ATP synthesis. Furthermore, KF also increased the expression of genes associated with ATP-binding cassette transporters, flagella, type III secretion system proteins, and DNA replication and repair, which may further influence nutrient uptake, motility, and growth. The results also revealed that KF decreased the expression of a broad range of virulence factors associated with LPS biosynthesis, iron homeostasis, cytotoxic pigment pyocyanin production, and motility and adhesion that are representative of an acute P. aeruginosa infection profile. In addition, P. aeruginosa pathways for amino acid synthesis and membrane lipid composition were modified to adapt to KF treatment. Overall, the present research provides a detailed view of P. aeruginosa adaptation and behaviour in response to KF and highlights the possible therapeutic approach of using plants to combat P. aeruginosa infections.
    Matched MeSH terms: Lipopolysaccharides
  11. Yam ML, Abdul Hafid SR, Cheng HM, Nesaretnam K
    Lipids, 2009 Sep;44(9):787-97.
    PMID: 19655189 DOI: 10.1007/s11745-009-3326-2
    Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.
    Matched MeSH terms: Lipopolysaccharides/pharmacology
  12. Seow SL, Naidu M, Sabaratnam V, Vidyadaran S, Wong KH
    Int J Med Mushrooms, 2017;19(5):405-418.
    PMID: 28845770 DOI: 10.1615/IntJMedMushrooms.v19.i5.30
    In Malaysia and China, the sclerotium of Lignosus rhinocerotis is used by local communities and traditional medicine practitioners as a general tonic and remedy to treat a variety of ailments, including inflammation-associated disorders. In this study, 10 samples from different preparations of L. rhinocerotis sclerotium, including a hot aqueous extract (HAE), an ethanol extract (EE), fractions from the HAE and EE, and crude polysaccharides, were tested for their in vitro cytotoxic and nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS)--stimulated BV2 microglia. Of the 10 samples tested, HAE was the least cytotoxic toward BV2 microglia, with a half-maximal inhibitory concentration of 176.23 ± 2.64 mg/mL at 24 hours of incubation and 20.01 ± 1.69 mg/ mL at 48 hours of incubation. The inhibition of NO production was explored by pretreatment of BV2 microglia with samples at 2 incubation time points (4 and 24 hours) before the stimulation by LPS for 24 hours. After 24 hours of pretreatment, 8 of the 10 samples inhibited NO production by 50% or more, and cytotoxic effects were not observed. Among the 8 active samples, 500 µg/mL of HAE, 250 µg/mL of an n-butanol fraction of the HAE, and 250 µg/mL of an ethyl acetate fraction of HAE showed maximum inhibition of NO production by 88.95%, 86.50%, and 85.93%, respectively. These results suggest that the L. rhinocerotis sclerotium may contain secondary metabolites that have the potential to inhibit NO production.
    Matched MeSH terms: Lipopolysaccharides
  13. Tham CL, Hazeera Harith H, Wai Lam K, Joong Chong Y, Singh Cheema M, Roslan Sulaiman M, et al.
    Eur J Pharmacol, 2015 Feb 15;749:1-11.
    PMID: 25560198 DOI: 10.1016/j.ejphar.2014.12.015
    2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC) has been proven to selectively inhibit the synthesis of proinflammatory mediators in lipopolysaccharide-induced U937 monocytes through specific interruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and improves the survival rate in a murine lethal sepsis model. The present study addressed the effects of BHMC upon lipopolysaccharide-induced endothelial dysfunction in human umbilical vein endothelial cells to determine the underlying mechanisms. The cytotoxicity effect of BHMC on HUVEC were determined by MTT assay. The effects of BHMC on endothelial dysfunction induced by lipopolysaccharide such as endothelial hyperpermeability, monocyte-endothelial adhesion, transendothelial migration, up-regulation of adhesion molecules and chemokines were evaluated. The effects of BHMC at transcriptional and post-translational levels were determined by Reverse Transcriptase-Polymerase Chain Reaction and Western Blots. The mode of action of BHMC was dissected by looking into the activation of Nuclear Factor-kappa B and Mitogen-Activated Protein Kinases. BHMC concentration-dependently reduced endothelial hyperpermeability, leukocyte-endothelial cell adhesion and monocyte transendothelial migration through inhibition of the protein expression of adhesion molecules (Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) and secretion of chemokines (Monocyte Chemotactic Protein-1) at the transcriptional level. BHMC restored endothelial dysfunction via selective inhibition of p38 Mitogen-Activated Protein Kinase enzymatic activity which indirectly prevents the activation of Nuclear Factor-kappaB and Activator Protein-1 transcription factors. These findings further support earlier observations on the inhibition of BHMC on inflammatory events through specific disruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and provide new insights into the inhibitory effects of BHMC on lipopolysaccharide-induced endothelial dysfunction.
    Matched MeSH terms: Lipopolysaccharides
  14. Ooi TC, Yaacob M, Rajab NF, Shahar S, Sharif R
    Saudi J Biol Sci, 2021 May;28(5):2987-2994.
    PMID: 34025176 DOI: 10.1016/j.sjbs.2021.02.039
    Oxidative stress, DNA damage, and unresolved inflammation are the predisposing factors of many chronic and degenerative diseases, including cancer. Stingless bee honey (SBH) is recognized to have high medicinal value by traditional medicine practitioners and has been used to treat various illnesses traditionally. This study aimed to determine the antioxidant, anti-inflammatory, and genoprotective effects of SBH by using in vitro cell culture models. The sugar content, total phenolic content, radical scavenging activity, and ferric reducing antioxidant power (FRAP) of SBH were determined in this study. Then, the protective effect of SBH against hydrogen peroxide (H2O2)-induced cell death and DNA damage was studied by using WIL2-NS human lymphoblastoid cell line, while the lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages cell line was used to study the anti-inflammatory effects of SBH. Results from this present study showed that the major sugar contents of SBH were fructose (19.39 + 0.01%) and glucose (14.03 ± 0.03%). Besides, the total phenolic content, the radical scavenging activity, and the FRAP value of SBH were 15.38 ± 0.02 mg GAE/100 g of honey, 34.04 ± 0.21%, and 206.77 + 1.76 μM AAE/100 g honey respectively. Pretreatment with SBH protected WIL2-NS cells from H2O2-induced cell death and DNA damage (p 
    Matched MeSH terms: Lipopolysaccharides
  15. Sosroseno W, Musa M, Ravichandran M, Fikri Ibrahim M, Bird PS, Seymour GJ
    Oral Microbiol. Immunol., 2006 Dec;21(6):347-52.
    PMID: 17064391
    The aim of the present study was to determine the role of cyclic adenosine monophosphate (cAMP) on arginase activity in a murine macrophage cell line (RAW264.7 cells) stimulated with lipopolysaccharide (LPS) from Actinobacillus actinomycetemcomitans.
    Matched MeSH terms: Lipopolysaccharides/pharmacology
  16. Giulioni C, Castellani D, Somani BK, Chew BH, Tailly T, Keat WOL, et al.
    World J Urol, 2023 May;41(5):1407-1413.
    PMID: 36930255 DOI: 10.1007/s00345-023-04363-6
    PURPOSE: To evaluate the perioperative outcomes of retrograde intra-renal surgery (RIRS) for lower pole stones (LPS) and factors affecting stone-free rate (SFR).

    METHODS: Data from 20 centers were retrospectively reviewed. Inclusion criteria were adult patients, normal renal anatomy, and LPS. Exclusion criteria were bilateral surgery, concomitant surgery for ureteral stones. SFR was defined as a single residual fragment (RF) ≤ 2 mm and evaluated 3-months after surgery. A multivariable logistic regression analysis was performed to assess factors associated with RF. Statistical significance was set at p value 

    Matched MeSH terms: Lipopolysaccharides
  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: Lipopolysaccharides*
  18. Yaw ACK, Chan EWL, Yap JKY, Mai CW
    J Cancer Res Clin Oncol, 2020 Sep;146(9):2219-2229.
    PMID: 32507974 DOI: 10.1007/s00432-020-03274-y
    PURPOSE: Pancreatic cancer is a lethal form of cancer that can be triggered by prolonged or acute inflammation of the pancreas. Inflammation have been shown to be regulated by a group of key protein molecules known as the inflammasomes. The NLRP3 inflammasome is the most studied inflammasome and have been strongly implicated to regulate cancer cell proliferation. Therefore, this study aimed to examine the regulation of NLRP3 inflammasome under LPS-induced inflammation and its role in modulating cell proliferation in a panel of pancreatic cancer cells.

    METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.

    RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.

    CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.

    Matched MeSH terms: Lipopolysaccharides/pharmacology
  19. Awaluddin R, Nugrahaningsih DAA, Solikhah EN
    Med J Malaysia, 2020 05;75(Suppl 1):10-13.
    PMID: 32471963
    INTRODUCTION: Diabetes mellitus is known as one of the risk factors for Idiopathic Pulmonary Fibrosis (IPF) development. Recently, metformin, the commonly used antidiabetic medication, is reported to have a therapeutic effect in IPF. However, the benefit of metformin therapy in IPF is still controversial. The study aims to investigate the metformin effect on the fibroblast and macrophage co-culture under lipopolysaccharides (LPS) and high glucose treatment.

    METHOD: The NIH 3T3 and RAW 264.7 co-culture were induced with LPS and high glucose before it was treated with metformin in different concentration. After 24 hours of treatment, the media and the cells were collected for further examination. The collagen expression was measured using Sirius red dye in the media. The IL-6 and TGF β mRNA examination were done using real-time PCR.

    RESULT: Our study showed that NIH 3T3 and RAW 264.7 coculture treated with metformin has higher collagen expression, but lower IL-6 mRNA expression compares to those on co-culture without treatment.

    CONCLUSION: Metformin increases fibrosis markers in LPS and high glucose-induced NIH 3T3 and RAW 264.7 coculture despite its ability to improve IL-6 mRNA expression.

    Matched MeSH terms: Lipopolysaccharides/metabolism
  20. Lee YY, Saba E, Irfan M, Kim M, Chan JY, Jeon BS, et al.
    Phytomedicine, 2019 Feb 15;54:169-181.
    PMID: 30668366 DOI: 10.1016/j.phymed.2018.09.186
    BACKGROUND: Different processing conditions alter the ginseng bioactive compounds, promoting or reducing its anti-inflammatory effects. We compared black ginseng (BG) - that have been steamed 5 times - with red ginseng (RG).

    HYPOTHESIS/ PURPOSE: To compare the anti-inflammatory activities and the anti-nociceptive properties of RG and BG.

    METHODS: Nitric Oxide (NO) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR), western blot, xylene-induced ear edema, carrageenan-induced paw edema RESULTS: The ginsenoside contents were confirmed using high-performance liquid chromatography (HPLC) and has been altered through increased processing. The highest concentration of these extracts inhibited NO production to near-basal levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 without exhibiting cytotoxicity. Pro-inflammatory cytokine expression at the mRNA level was investigated using qRT-PCR. Comparatively, BG exhibited better inhibition of pro-inflammatory mediators, iNOS and COX-2 and pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α. Protein expression was determined using western blot analysis and BG exhibited stronger inhibition. Xylene-induced ear edema model in mice and carrageenan-induced paw edema in rats were carried out and tested with the effects of ginseng as well as dexamethasone and indomethacin - commonly used drugs. BG is a more potent anti-inflammatory agent, possesses anti-nociceptive properties, and has a strong potency comparable to the NSAIDs.

    CONCLUSION: BG has more potent anti-inflammatory and anti-nociceptive effects due to the change in ginsenoside component with increased processing.

    Matched MeSH terms: Lipopolysaccharides/pharmacology
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