scholarly journals Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

2006 ◽  
Vol 85 (5) ◽  
pp. 452-456 ◽  
Author(s):  
M.M. Zavarella ◽  
O. Gbemi ◽  
J.D. Walters
Keyword(s):  
Steady State ◽  
Connective Tissue ◽  
Inflammatory Mediator ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Temperature Dependent ◽  
Tnf Α ◽  
Steady State Levels ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 μg/mL and a Vmax of 1.42 ng/min/μg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-α. In humans, systemically administered naproxen attained steady-state levels of 61.9 μg/mL in blood and 9.4 μg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 μg/mL and 1.5 μg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non smokers by No2

1997 ◽  
Vol 16 (10) ◽  
pp. 577-588 ◽  
Author(s):  
Tiziana Dandrea ◽  
Ba Tu ◽  
Anders Blomberg ◽  
Thomas Sandström ◽  
Magnus Sköld ◽  
...  
Keyword(s):  
Steady State ◽  
Alveolar Macrophages ◽  
Exposure Model ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α ◽  
Dependent Inhibition ◽  
Steady State Levels ◽  
Dose Dependent

Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture super natants were collected 4 h after the exposure and assayed for secreted TNF-α, IL-1β, IL-8 and MIP-1α. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-α and IL-1β, but not IL-8 (MIP-1α not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-,1.5- and 3-fold the amounts of IL-1β, IL-8, TNF-α and MIP-1α, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration- dependent inhibition of the secretion of all cytokines except IL-1β from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-α from non-smoker's cells was inhibited by the gas in a concentration- dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-α. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1β mRNA. However, exposure to the gas inhibited LPS- induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcrip tional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.

scholarly journals Extracts of Andrographis paniculata (Burm.f.) Nees Leaves Exert Anti-Gout Effects by Lowering Uric Acid Levels and Reducing Monosodium Urate Crystal-Induced Inflammation

2022 ◽  
Vol 12 ◽  
Author(s):  
Eldiza Puji Rahmi ◽  
Endang Kumolosasi ◽  
Juriyati Jalil ◽  
Fhataheya Buang ◽  
Jamia Azdina Jamal
Keyword(s):  
Uric Acid ◽  
Synovial Fluid ◽  
Western Blot ◽  
Inflammatory Mediator ◽  
Dependent Manner ◽  
Monosodium Urate ◽  
Tnf Α ◽  
Swelling Rate ◽  
Anti Inflammatory

Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.

scholarly journals Bioactivity-Guided Extract Optimization of Osmanthus fragrans var. aurantiacus Leaves and Anti-Inflammatory Activities of Phillyrin

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1545
Author(s):  
Hwa-Young Song ◽  
Da-Eun Jeong ◽  
Mina Lee
Keyword(s):  
Biological Activities ◽  
Radical Scavenging ◽  
No Production ◽  
Dependent Manner ◽  
Optimal Method ◽  
Concentration Dependent Manner ◽  
Osmanthus Fragrans ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Extracellular Regulated Kinase

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

scholarly journals Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangqiang Zhao ◽  
Duanfeng Jiang ◽  
Xiaoying Sun ◽  
Qiuyu Mo ◽  
Shaobin Chen ◽  
...  
Keyword(s):  
Mesoporous Silica Nanoparticles ◽  
Treatment Options ◽  
Inflammatory Factors ◽  
Main Method ◽  
Tnf Α ◽  
Good Biocompatibility ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Lymphoma Therapy

Abstract Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

scholarly journals Evaluation of Antioxidant, Anti-Inflammatory and Cytoprotective Properties of Ethanolic Mint Extracts from Algeria on 7-Ketocholesterol-Treated Murine RAW 264.7 Macrophages

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 184 ◽  
Author(s):  
Fatiha Brahmi ◽  
Thomas Nury ◽  
Meryam Debbabi ◽  
Samia Hadj-Ahmed ◽  
Amira Zarrouk ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Total Phenolic Content ◽  
Phenolic Content ◽  
Cytokine Secretion ◽  
Total Phenolic ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Raw 264.7 Macrophages ◽  
Tnf Α ◽  
Anti Inflammatory

The present study consisted in evaluating the antioxidant, anti-inflammatory and cytoprotective properties of ethanolic extracts from three mint species (Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L.) Huds (MR)) with biochemical methods on murine RAW 264.7 macrophages (a transformed macrophage cell line isolated from ascites of BALB/c mice infected by the Abelson leukemia virus). The total phenolic, flavonoid and carotenoid contents were determined with spectrophotometric methods. The antioxidant activities were quantified with the Kit Radicaux Libres (KRLTM), the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The MS extract showed the highest total phenolic content, and the highest antioxidant capacity, while the MR extract showed the lowest total phenolic content and the lowest antioxidant capacity. The cytoprotective and anti-inflammatory activities of the extracts were quantified on murine RAW 264.7 macrophages treated with 7-ketocholesterol (7KC; 20 µg/mL: 50 µM) associated or not for 24 h and 48 h with ethanolic mint extracts used at different concentrations (25, 50, 100, 200 and 400 µg/mL). Under treatment with 7KC, an important inhibition of cell growth was revealed with the crystal violet test. This side effect was strongly attenuated in a dose dependent manner with the different ethanolic mint extracts, mainly at 48 h. The most important cytoprotective effect was observed with the MS extract. In addition, the effects of ethanolic mint extracts on cytokine secretion (Interleukin (IL)-6, IL-10, Monocyte Chemoattractant Protein (MCP)-1, Interferon (IFN)-ϒ, Tumor necrosis factor (TNF)-α) were determined at 24 h on lipopolysaccharide (LPS, 0.2 µg/mL)-, 7KC (20 µg/mL)- and (7KC + LPS)-treated RAW 264.7 cells. Complex effects of mint extracts were observed on cytokine secretion. However, comparatively to LPS-treated cells, all the extracts strongly reduce IL-6 secretion and two of them (MP and MR) also decrease MCP-1 and TNF-α secretion. However, no anti-inflammatory effects were observed on 7KC- and (7KC + LPS)-treated cells. Altogether, these data bring new evidences on the potential benefits (especially antioxidant and cytoprotective properties) of Algerian mint on human health.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

scholarly journals Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

scholarly journals Anti-inflammatory and Matrix Metallopeptidase-1-Inhibitory Effects of the Cassia obtusifolia L. Seed Extract on Particulate Matter-induced Skin

2021 ◽  
Vol 19 (3) ◽  
pp. 355-363
Author(s):  
Jung-Wook Kang ◽  
In-Chul Lee
Keyword(s):  
Particulate Matter ◽  
Seed Extract ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Cassia Obtusifolia ◽  
Tnf Α ◽  
Matrix Metallopeptidase ◽  
Anti Inflammatory

Purpose: This study aimed to investigate the effects of the Cassia obtusifolia L. seed extract (CSE) on particulate matter (PM)-induced skin.Methods: The effects of CSE on cell viability were evaluated using a skin cell line. To determine the anti-inflammatory effects and matrix metallopeptidase-1 (MMP-1)-inhibitory effects of CSE on PM-induced skin, NO and MMP-1 expressions were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the effects of CSE was investigated the induction of IL-8 and TNF-α treated PM on reconstructed human full thickness skin models.Results: It was observed that CSE decreased NO production in PM-induced RAW 264.7 cells without cytotoxicity. In addition, CSE decreased the expression of MMP-1 in PM-induced cells in a dose-dependent manner. CSE decreased IL-8 and TNF-α production in a PM-reconstructed human skin model.Conclusion: These results indicate that CSE could be used as a cosmetic material to induce anti-inflammation and inhibition of MMP-1 in PM-induced skin.

scholarly journals Peran Kurkumin Sebagai Terapi Pada Osteoartritis

2020 ◽  
Vol 2 (1) ◽  
pp. 106-110
Author(s):  
Rilianda Abelira
Keyword(s):  
Peptic Ulcer ◽  
Side Effects ◽  
Old Age ◽  
Cyclooxygenase 2 ◽  
Tnf Α ◽  
The World ◽  
Inflammatory Drugs ◽  
Digestive Disorders ◽  
Cox 2 ◽  
Anti Inflammatory

Osteoartritis (OA) merupakan salah satu penyakit penyakit degeneratif atau geriatri yang disebabkan adanya inflamasi yang melibatkan kartilago, lapisan sendi, ligamen, dan tulang yang akibatnya dapat menyebabkan nyeri dan kekakuan pada sendi. Epidemiologi OA di didunia sekitar 15% dengan usia diatas 65-75 dan diperkirakan pada tahun 2020 penderita osteoarthritis akan meningkat 11,6 juta penderita. Kejadian OA di Indonesia dari tahun 1990 hingga 2010 telah mengalami peningkatan sebanyak 44,2% dan berdasarkan usia di Indonesia cukup tinggi dengan 65% pada usia tua (lansia) atau lebih dari 61 tahun. Pengobatan secara farmakologis untuk OA dengan menggunakan Obat Anti Inflamasi Non-Steroid (OAINS) salah satu contohnya adalah meloksikam. Namun, efek samping penggunaan OAINS dapat menimbulkan beberapa masalah seperti timbulnya ulkus peptikum dan gangguan pencernaan. Hal ini menyebabkan sedang dikembangkannya pengobatan herbal untuk OA yang harapannya dapat menjadi pengobatan utama dalam mengatasi OA dengan menggunakan kurkumin. Kurkumin berperan sebagai antiinflamasi dalam kunyit putih dengan menurunkan aktivitas cyclooxygenase 2(COX-2), lipoxygenase dan menghambat produksi sitokin seperti TNF-α, interleukin (IL). Osteoarthritis (OA) is a degenerative or geriatric disease that is caused by inflammation involving cartilages, joint lining, ligaments, and bones which can cause pain and stiffness in the joints. Epidemiology of OA in the world around 15% with ages above 65-75 and it is estimated in 2020, osteoarthritis will increase by 11.6 million. The incidence of OA in Indonesia from 1990 to 2010 has increased by 44.2% and by age in Indonesia is quite high with 65% in old age (elderly) or more than 61 years. Treatment for OA is using non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam. However, side effects of NSAID use can cause several problems such as the emergence of peptic ulcer and digestive disorders. This has led to the development of herbal treatments for OA which hopes to become the main treatment in overcoming OA by using curcumin. Curcumin acts as an anti-inflammatory in white turmeric by reducing the activity of cyclooxygenase 2 (COX-2), lipoxygenase and inhibiting the production of cytokines such as TNF-α, interleukin (IL).

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