Displaying publications 1 - 20 of 78 in total

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  1. Mohd Faudzi SM, Leong SW, Auwal FA, Abas F, Wai LK, Ahmad S, et al.
    Arch Pharm (Weinheim), 2021 Jan;354(1):e2000161.
    PMID: 32886410 DOI: 10.1002/ardp.202000161
    A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.
    Matched MeSH terms: Macrophages/drug effects
  2. van Sleen Y, Jiemy WF, Pringle S, van der Geest KSM, Abdulahad WH, Sandovici M, et al.
    Arthritis Rheumatol, 2021 12;73(12):2327-2337.
    PMID: 34105308 DOI: 10.1002/art.41887
    OBJECTIVE: Macrophages mediate inflammation, angiogenesis, and tissue destruction in giant cell arteritis (GCA). Serum levels of the macrophage-associated protein YKL-40 (chitinase 3-like protein 1), previously linked to angiogenesis and tissue remodeling, remain elevated in GCA despite glucocorticoid treatment. This study was undertaken to investigate the contribution of YKL-40 to vasculopathy in GCA.

    METHODS: Immunohistochemistry was performed on GCA temporal artery biopsy specimens (n = 12) and aortas (n = 10) for detection of YKL-40, its receptor interleukin-13 receptor α2 (IL-13Rα2), macrophage markers PU.1 and CD206, and the tissue-destructive protein matrix metalloproteinase 9 (MMP-9). Ten noninflamed temporal artery biopsy specimens served as controls. In vitro experiments with granulocyte-macrophage colony-stimulating factor (GM-CSF)- or macrophage colony-stimulating factor (M-CSF)-skewed monocyte-derived macrophages were conducted to study the dynamics of YKL-40 production. Next, small interfering RNA-mediated knockdown of YKL-40 in GM-CSF-skewed macrophages was performed to study its effect on MMP-9 production. Finally, the angiogenic potential of YKL-40 was investigated by tube formation experiments using human microvascular endothelial cells (HMVECs).

    RESULTS: YKL-40 was abundantly expressed by a CD206+MMP-9+ macrophage subset in inflamed temporal arteries and aortas. GM-CSF-skewed macrophages from GCA patients, but not healthy controls, released significantly higher levels of YKL-40 compared to M-CSF-skewed macrophages (P = 0.039). In inflamed temporal arteries, IL-13Rα2 was expressed by macrophages and endothelial cells. Functionally, knockdown of YKL-40 led to a 10-50% reduction in MMP-9 production by macrophages, whereas exposure of HMVECS to YKL-40 led to significantly increased tube formation.

    CONCLUSION: In GCA, a GM-CSF-skewed, CD206+MMP-9+ macrophage subset expresses high levels of YKL-40 which may stimulate tissue destruction and angiogenesis through IL-13Rα2 signaling. Targeting YKL-40 or GM-CSF may inhibit macrophages that are currently insufficiently suppressed by glucocorticoids.

    Matched MeSH terms: Macrophages/drug effects
  3. Othman AR, Abdullah N, Ahmad S, Ismail IS, Zakaria MP
    PMID: 25652309 DOI: 10.1186/s12906-015-0528-4
    BACKGROUND: The Jatropha curcas plant or locally known as "Pokok Jarak" has been widely used in traditional medical applications. This plant is used to treat various conditions such as arthritis, gout, jaundice, wound and inflammation. However, the nature of compounds involved has not been well documented. Hence, this study was conducted to investigate the anti-inflammatory activity of different parts of J. curcas plant and to identify the active compounds involved.
    METHODS: In this study, methanol (80%) extraction of four different parts (leaves, fruits, stem and root) of J. curcas plant was carried out. Phenolic content of each part was determined by using Folin-Ciocalteau reagent. Gallic acid was used as the phenol standard. Each plant part was screened for anti-inflammatory activity using cultured macrophage RAW 264.7 cells. The active plant part was then partitioned with hexane, chloroform, ethyl acetate and water. Each partition was again screened for anti-inflammatory activity. The active partition was then fractionated using an open column chromatography system. Single spots isolated from column chromatography were assayed for anti-inflammatory and cytotoxicity activities. Spots that showed activity were subjected to gas chromatography mass spectrophotometry (GC-MS) analysis for identification of active metabolites.
    RESULTS: The hexane partition from root extract showed the highest anti-inflammatory activity. However, it also showed high cytotoxicity towards RAW 264.7 cells at 1 mg/mL. Fractionation process using column chromatography showed five spots. Two spots labeled as H-4 and H-5 possessed anti-inflammatory activity, without cytotoxicity activity. Analysis of both spots by GC-MS showed the presence of hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid.
    CONCLUSION: This finding suggests that hexadecanoic acid methyl ester, octadecanoic acid methyl ester and octadecanoic acid could be responsible for the anti-inflammatory activity of the J. curcas root extract.
    Matched MeSH terms: Macrophages/drug effects*
  4. Abood WN, Fahmi I, Abdulla MA, Ismail S
    PMID: 24969238 DOI: 10.1186/1472-6882-14-205
    Immunomodulators are substances that modify immune system response to a threat. Immunomodulators modulate and potentiate the immune system, keeping it highly prepared for any threat. The immunomodulatory effect of the traditional medicine Tinospora crispa is investigated in this work.
    Matched MeSH terms: Macrophages/drug effects
  5. Hendra R, Ahmad S, Oskoueian E, Sukari A, Shukor MY
    PMID: 22070850 DOI: 10.1186/1472-6882-11-110
    Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities.
    Matched MeSH terms: Macrophages/drug effects
  6. Harikrishnan H, Jantan I, Haque MA, Kumolosasi E
    BMC Complement Altern Med, 2018 Jul 25;18(1):224.
    PMID: 30045725 DOI: 10.1186/s12906-018-2289-3
    BACKGROUND: Phyllanthus amarus has been used widely in various traditional medicines to treat swelling, sores, jaundice, inflammatory diseases, kidney disorders, diabetes and viral hepatitis, while its pharmacological and biochemical mechanisms underlying its anti-inflammatory properties have not been well investigated. The present study was carried out to investigate the effects of 80% ethanolic extract of P. amarus on pro-inflammatory mediators release in nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling activation in lipopolysaccharide (LPS)-induced U937 human macrophages.

    METHODS: The release of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in a culture supernatant was determined by ELISA. Determination of cyclooxygenase-2 (COX-2) protein and the activation of MAPKs molecules (JNK, ERK and p38 MAPK), NF-κB and Akt in LPS-induced U937 human macrophages were investigated by immunoblot technique. The relative gene expression levels of COX-2 and pro-inflammatory cytokines were measured by using qRT-PCR. The major metabolites of P. amarus were qualitatively and quantitatively analyzed in the extract by using validated reversed-phase high performance liquid chromatography (HPLC) methods.

    RESULTS: P. amarus extract significantly inhibited the production of pro-inflammatory mediators (TNF-α, IL-1β, PGE2) and COX-2 protein expression in LPS-induced U937 human macrophages. P. amarus-pretreatment also significantly downregulated the increased mRNA transcription of pro-inflammatory markers (TNF-α, IL-1β, and COX-2) in respective LPS-induced U937 macrophages. It downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β and restored the degradation of IκBα, and attenuated the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a dose-dependent manner. P. amarus extract also downregulated the expression of upstream signaling molecules, TLR4 and MyD88, which play major role in activation of NF-κB, MAPK and PI3K-Akt signaling pathways. The quantitative amounts of lignans, phyllanthin, hypophyllahtin and niranthin, and polyphenols, gallic acid, geraniin, corilagin, and ellagic acid in the extract were determined by HPLC analysis.

    CONCLUSION: The study revealed that P. amarus targeted the NF-κB, MAPK and PI3K-Akt signaling pathways to exert its anti- inflammatory effects by downregulating the prospective inflammatory signaling mediators.

    Matched MeSH terms: Macrophages/drug effects
  7. Baskaran A, Chua KH, Sabaratnam V, Ravishankar Ram M, Kuppusamy UR
    BMC Complement Altern Med, 2017 Jan 13;17(1):40.
    PMID: 28086773 DOI: 10.1186/s12906-016-1546-6
    Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H2O2)-induced inflammation on RAW 264.7 macrophages was investigated.
    Matched MeSH terms: Macrophages/drug effects*
  8. BenSaad LA, Kim KH, Quah CC, Kim WR, Shahimi M
    BMC Complement Altern Med, 2017 Jan 14;17(1):47.
    PMID: 28088220 DOI: 10.1186/s12906-017-1555-0
    Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells.
    Matched MeSH terms: Macrophages/drug effects
  9. 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: Macrophages/drug effects*
  10. Bukhari SN, Lauro G, Jantan I, Bifulco G, Amjad MW
    Bioorg Med Chem, 2014 Aug 1;22(15):4151-61.
    PMID: 24938495 DOI: 10.1016/j.bmc.2014.05.052
    Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel α,β-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A₂ (sPLA₂), cyclooxygenases (COX), soybean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-α. Six α,β-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14) exhibited strong inhibition of sPLA₂ activity, with IC₅₀ values in the range of 2.19-8.76 μM. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with IC₅₀ values ranging from 0.37 to 1.77 μM (lower than that of reference compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All compounds were evaluated for the inhibitory activities against LPS-induced TNF-α and IL-6 release in the macrophages. On the basis of screening results, five active compounds 3, 4, 12, 13 and 14 were found strong inhibitors of TNF-α and IL-6 release in a dose-dependent manner. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX and LOX inhibitory activities of the investigated compounds. Present findings increases the possibility that these α,β-unsaturated carbonyl based compounds might serve as beneficial starting point for the design and development of improved anti-inflammatory agents.
    Matched MeSH terms: Macrophages/drug effects
  11. Mohd Aluwi MF, Rullah K, Yamin BM, Leong SW, Abdul Bahari MN, Lim SJ, et al.
    Bioorg Med Chem Lett, 2016 05 15;26(10):2531-8.
    PMID: 27040659 DOI: 10.1016/j.bmcl.2016.03.092
    The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.
    Matched MeSH terms: Macrophages/drug effects*
  12. Leong SW, Mohd Faudzi SM, Abas F, Mohd Aluwi MF, Rullah K, Lam KW, et al.
    Bioorg Med Chem Lett, 2015 Aug 15;25(16):3330-7.
    PMID: 26071636 DOI: 10.1016/j.bmcl.2015.05.056
    A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.
    Matched MeSH terms: Macrophages/drug effects*
  13. Bukhari SN, Zhang X, Jantan I, Zhu HL, Amjad MW, Masand VH
    Chem Biol Drug Des, 2015 Jun;85(6):729-42.
    PMID: 25328063 DOI: 10.1111/cbdd.12457
    A novel series of 1,3-diphenyl-2-propen-1-one (chalcone) derivatives was synthesized by a simple, eco-friendly, and efficient Claisen-Schmidt condensation reaction and used as precursors for the synthesis of new pyrazoline derivatives. All the synthesized compounds were screened for anti-inflammatory related activities such as inhibition of phospholipase A(2) (PLA(2)), cyclooxygenases (COX-1 and COX-2), IL-6, and TNF-α. The results of the above studies show that the compounds synthesized are effective inhibitors of above pro-inflammatory enzymes and cytokines. Overall, the results of the studies reveal that the pyrazolines with chlorophenyl substitution (1b-6b) seem to be important for inhibition of enzymes and cytokines. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX-inhibitory activities of the investigated compounds.
    Matched MeSH terms: Macrophages/drug effects
  14. Mehta M, Deeksha, Sharma N, Vyas M, Khurana N, Maurya PK, et al.
    Chem Biol Interact, 2019 May 01;304:10-19.
    PMID: 30849336 DOI: 10.1016/j.cbi.2019.02.021
    Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
    Matched MeSH terms: Macrophages/drug effects*
  15. Zengin G, Rodrigues MJ, Abdallah HH, Custodio L, Stefanucci A, Aumeeruddy MZ, et al.
    Comput Biol Chem, 2018 Dec;77:178-186.
    PMID: 30336375 DOI: 10.1016/j.compbiolchem.2018.10.005
    The genus Silene is renowned in Turkey for its traditional use as food and medicine. Currently, there are 138 species of Silene in Turkey, amongst which have been several studies for possible pharmacological potential and application in food industry. However, there is currently a paucity of data on Silene salsuginea Hub.-Mor. This study endeavours to access its antioxidant, enzyme inhibitory, and anti-inflammatory properties. Besides, reversed-phase high-performance liquid chromatography-diode array detector (RP-HPLC-DAD) was used to detect phenolic compounds, and molecular docking was performed to provide new insights for tested enzymes and phenolics. High amounts of apigenin (534 μg/g extract), ferulic acid (452 μg/g extract), p-coumaric acid (408 μg/g extract), and quercetin (336 μg/g extract) were detected in the methanol extract while rutin (506 μg/g extract) was most abundant in the aqueous extract. As for their biological properties, the methanol extract exhibited the best antioxidant effect in the DPPH and CUPRAC assays, and also the highest inhibition against tyrosinase. The aqueous extract was the least active enzyme inhibitor but showed the highest antioxidant efficacy in the ABTS, FRAP, and metal chelating assays. At a concentration of 15.6 μg/mL, the methanol extract resulted in a moderate decrease (25.1%) of NO production in lipopolysaccharide-stimulated cells. Among the phenolic compounds, epicatechin, (+)-catechin, and kaempferol showed the highest binding affinity towards the studied enzymes in silico. It can be concluded that extracts of S. salsuginea are a potential source of functional food ingredients but need further analytical experiments to explore its complexity of chemical compounds and pharmacological properties as well as using in vivo toxicity models to establish its maximum tolerated dose.
    Matched MeSH terms: Macrophages/drug effects
  16. Shah K, Chan LW, Wong TW
    Drug Deliv, 2017 Nov;24(1):1631-1647.
    PMID: 29063794 DOI: 10.1080/10717544.2017.1384298
    The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
    Matched MeSH terms: Macrophages/drug effects
  17. Achoui M, Heyninck K, Looi CY, Mustafa AM, Haegeman G, Mustafa MR
    Drug Des Devel Ther, 2014;8:1993-2007.
    PMID: 25349474 DOI: 10.2147/DDDT.S68659
    The terpenoid 17-O-acetylacuminolide (AA) was shown to inhibit the production of several inflammatory mediators. However, the mechanisms by which this compound elicited its anti-inflammatory activity remain to be elucidated. In this study, we analyzed the effects of AA on inflammatory gene expression in two different cell types with primordial importance in the inflammatory processes - endothelial cells and macrophages. In human umbilical vein endothelial cells, AA inhibited the expression of inflammatory proteins including the adhesion molecules intercellular adhesion molecule 1; vascular cell adhesion molecule 1; and E-selectin, as well as the release of the chemokine interleukin-8. Additionally, AA hindered the formation of capillary-like tubes in an in vitro model of angiogenesis. AA's effects in endothelial cells can be attributed at least in part to AA's inhibition of tumor necrosis factor alpha-induced nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)'s translocation. Also, in lipopolysaccharide-stimulated macrophage-like RAW264.7 cells, AA was able to downregulate the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase, interleukin-6, and chemokine (C-C motif) ligand 2. Moreover, AA inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), IκB kinase (IKK), and the mitogen-activated protein kinases JNK, ERK, and p38. In conclusion, the present results further support the anti-inflammatory potential of AA in different models of inflammation.
    Matched MeSH terms: Macrophages/drug effects*
  18. Jantan I, Bukhari SN, Adekoya OA, Sylte I
    Drug Des Devel Ther, 2014;8:1405-18.
    PMID: 25258510 DOI: 10.2147/DDDT.S67370
    Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A2, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents.
    Matched MeSH terms: Macrophages/drug effects
  19. Adewoyin M, Mohsin SM, Arulselvan P, Hussein MZ, Fakurazi S
    Drug Des Devel Ther, 2015;9:2475-84.
    PMID: 25995619 DOI: 10.2147/DDDT.S72716
    BACKGROUND: Cinnamic acid (CA) is a phytochemical originally derived from Cinnamomum cassia, a plant with numerous pharmacological properties. The intercalation of CA with a nanocarrier, zinc layered hydroxide, produces cinnamate-zinc layered hydroxide (ZCA), which has been previously characterized. Intercalation is expected to improve the solubility and cell specificity of CA. The nanocarrier will also protect CA from degradation and sustain its release. The aim of this study was to assess the effect of intercalation on the anti-inflammatory capacity of CA.

    METHODS: In this study, the anti-inflammatory activity of ZCA was investigated and compared with that of nonintercalated CA. Evaluations were based on the capacity of ZCA and CA to modulate the release of nitric oxide, prostaglandin E2, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β, and IL-10 in lipopolysaccharide-induced RAW 264.7 cells. Additionally, the expression of proinflammatory enzymes, ie, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B (NF-κB), were examined.

    RESULTS: Although both ZCA and CA downregulated nitric oxide, prostaglandin E2, tumor necrosis factor alpha, IL-1β, and IL-6, ZCA clearly displayed better activity. Similarly, expression of cyclooxygenase-2 and inducible nitric oxide synthase were inhibited in samples treated with ZCA and CA. The two compounds effectively inactivated the transcription factor NF-κB, but the anti-inflammatory cytokine, IL-10, was significantly upregulated by ZCA only.

    CONCLUSION: The present findings suggest that ZCA possesses better anti-inflammatory potential than CA, while zinc layered hydroxide had little or no effect, and these results were comparable with the positive control.

    Matched MeSH terms: Macrophages/drug effects*
  20. 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: Macrophages/drug effects
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