Selenium Nanoparticles Dispersed in Phytochemical Exert Anti-Inflammatory Activity by Modulating Catalase, GPx1, and COX-2 Gene Expression in a Rheumatoid Arthritis Rat Model

Background: 4-Aminoquinoline derivatives possess various potential biological properties.The introduction of additional piperazine heterocyclic pharmacophoric moiety tends to haveprofound impact in increasing the activity. The present work was undertaken to investigate thein-vitro and in-vivo anti-inflammatory activity as well as the peripheral and central analgesicactivities of compound 1-(4-(7-chloroquinoline-4-yl)piperazin-1-yl)-2-(4-phenylpiperazin-1-yl)ethanone (5) in experimental models. Methods: The percentage inhibition of the lipopolysaccharide induced NO release of 7-chloro-4-(piperazin-1-yl)quinoline derivatives 1-9 was determined in RAW 264.7 murine macrophagemodel. Western blot analysis was performed to evaluate the effect of compound 5 on proteinexpression of inducible nitric oxide synthase (iNOS). Gene expression of inflammatory markerswas evaluated using real-time polymerase chain reaction. The peripheral and central analgesicactivities of compound 5 were evaluated in mice using writhing and hot-plate tests, respectively.Anti-inflammatory activity was assessed using carrageenan-induced paw edema assay in miceand serum NO and COX-2 levels were measured. Results: Compound 5 demonstrated the highest NO inhibitory activity that was accompaniedby inhibition of iNOS protein expression and decreased gene expression levels of inflammatorymarkers. It revealed a potential peripheral analgesic effect through inhibition of abdominalwrithing in mice treated with doses of 15 and 30 mg/kg and its effect was comparable to diclofenacsodium. Compound 5 possessed an analgesic activity starting from 15 min post administrationand reached its peak at 45 min which was significantly higher than that of tramadol hydrochloridesuggesting its potential as central analgesic agent. It also showed percentage of inhibition ofedema of 34, 50 and 64% at 1, 2, and 3 h respectively, post carrageenan challenge together with asignificant decrease in serum NO and COX-2 levels. Conclusion: The remarkable anti-inflammatory and analgesic activities of compound 5 couldbe attributed to the advantageous introduction of the heterocyclic 7-chloro-4-(piperazin1-yl)quinoline scaffold incorporated with N-phenylpiperzine functional groups linked together withthe ethanone pharmacophoric chain.

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Faculty Opinions recommendation of Anti-inflammatory activity of monogalactosyldiacylglycerol in human articular cartilage in vitro: activation of an anti-inflammatory cyclooxygenase-2 (COX-2) pathway.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13272062.14628172 ◽

2011 ◽

Author(s):

Johanne Martel-Pelletier ◽

Hassan Fahmi

Keyword(s):

Articular Cartilage ◽

Cyclooxygenase 2 ◽

Inflammatory Activity ◽

Human Articular Cartilage ◽

In Vitro Activation ◽

Cox 2 ◽

Anti Inflammatory

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Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178617999201106113114 ◽

2020 ◽

Vol 17 ◽

Author(s):

Deepak Kumar Singh ◽

Mayank Kulshreshtha ◽

Yogesh Kumar ◽

Pooja A Chawla ◽

Akash Ved ◽

...

Keyword(s):

Molecular Docking ◽

Biological Activities ◽

Inflammatory Activity ◽

Standard Drug ◽

Docking Score ◽

Chemical Structures ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

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Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

International Journal of Molecular Sciences ◽

10.3390/ijms22031022 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1022

Author(s):

Tatyana P. Makalish ◽

Ilya O. Golovkin ◽

Volodymyr V. Oberemok ◽

Kateryna V. Laikova ◽

Zenure Z. Temirova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Rat Model ◽

Peripheral Blood ◽

Antisense Oligonucleotide ◽

Joint Inflammation ◽

Blood Concentrations ◽

Tnf Α ◽

Effective Drugs ◽

First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

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Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

Scientia Pharmaceutica ◽

10.3390/scipharm89020022 ◽

2021 ◽

Vol 89 (2) ◽

pp. 22

Author(s):

Mariia Mishchenko ◽

Sergiy Shtrygol’ ◽

Andrii Lozynskyi ◽

Semen Khomyak ◽

Volodymyr Novikov ◽

...

Keyword(s):

Drug Design ◽

Anticonvulsant Activity ◽

Inflammatory Activity ◽

Significant Protection ◽

Protection Level ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Target Agent

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

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Anti-Inflammatory Effects of Abeliophyllum distichum Nakai (Cultivar Okhwang 1) Callus through Inhibition of PI3K/Akt, NF-κB, and MAPK Signaling Pathways in Lipopolysaccharide-Induced Macrophages

Processes ◽

10.3390/pr9061071 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1071

Author(s):

Tae-Won Jang ◽

Jae-Ho Park

Keyword(s):

Gene Expression ◽

Polymerase Chain Reaction ◽

Signaling Pathways ◽

Chain Reaction ◽

Inos Gene ◽

Polymerase Chain ◽

Cox 2 ◽

Anti Inflammatory ◽

Abeliophyllum Distichum ◽

Inos Gene Expression

One of the Korean endemic plants, Abeliophyllum distichum Nakai (Oleaceae), contains acteoside, which is a glycoside exhibiting neuroprotective, anti-inflammation effects and antibacterial capacities. We conducted an investigation on the effects of the callus of A. distichum (cultivar Okhwang 1, CAO) on pro-inflammatory mediators released following nuclear factor-кB (NF-кB), phosphatidylinositol 3-kinase/Akt (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signal activation in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Immunoblotting was employed to find out the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and activation of MAPK molecules, NF-κB and Akt. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. High-performance liquid chromatography revealed that CAO was rich in acteoside and isoacteoside. As a result, CAO inhibited the generation of NO, cytokines, COX-2, and iNOS expression. Further, translocation to the nuclear of NF-κB p65 and degradation of the inhibitor of NF-кB (IкB) were alleviated by suppressing phosphorylation. Additionally, CAO significantly impacted MAPK pathway activation by potentially reducing phosphorylation of MAPKs. These results indicate that the anti-inflammatory effect of CAO is mediated via the inhibition of MAPK, PI3K/Akt, and NF-κB signaling pathways, probably via glycosides, phenolics, and flavonoids bioactivity derived from plants. CAO can serve as a potential anti-inflammatory agent, which alleviates inflammation factors and act through specific cell signaling pathways.

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VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis

Molecular and Cellular Biochemistry ◽

10.1007/s11010-012-1488-3 ◽

2012 ◽

Vol 374 (1-2) ◽

pp. 1-11 ◽

Cited By ~ 78

Author(s):

Cong Dai ◽

Chang-Qing Zheng ◽

Fan-ji Meng ◽

Zheng Zhou ◽

Li-xuan Sang ◽

...

Keyword(s):

Rat Model ◽

Inflammatory Activity ◽

Anti Inflammatory

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Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile

Bioorganic Chemistry ◽

10.1016/j.bioorg.2018.02.018 ◽

2018 ◽

Vol 77 ◽

pp. 568-578 ◽

Cited By ~ 18

Author(s):

Khaled R.A. Abdellatif ◽

Wael A.A. Fadaly ◽

Yaseen A.M.M. Elshaier ◽

Waleed A.M. Ali ◽

Gehan M. Kamel

Keyword(s):

Safety Profile ◽

Inflammatory Activity ◽

Pyrazole Derivatives ◽

Cox 2 ◽

Anti Inflammatory

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Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000480527 ◽

2017 ◽

Vol 43 (2) ◽

pp. 540-552 ◽

Cited By ~ 17

Author(s):

Hany H. Arab ◽

Samir A. Salama ◽

Tamer M. Abdelghany ◽

Hany A. Omar ◽

El-Shaimaa A. Arafa ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mapk Pathway ◽

Lipid Peroxide ◽

Mitogen Activated Protein Kinase ◽

Camel Milk ◽

Tnf Α ◽

Mitogen Activated Protein ◽

Anti Oxidant ◽

Cox 2 ◽

Anti Inflammatory

Background/Aims: Camel milk (CM) has shown beneficial anti-inflammatory actions in several experimental and clinical settings. So far, its effect on rheumatoid arthritis (RA) has not been previously explored. Thus, the current work aimed to evaluate the effects of CM in Adjuvant-induced arthritis and air pouch edema models in rats, which mimic human RA. Methods: CM was administered at 10 ml/kg orally for 3 weeks starting on the day of Freund’s adjuvant paw inoculation. The levels of TNF-α and IL-10 were measured by ELISA while the protein expression of NF-κBp65, COX-2 and iNOS was detected by immunohistochemistry. The expression of MAPK target proteins was assessed by Western blotting. Results: CM attenuated paw edema, arthritic index and gait score along with dorsal pouch inflammatory cell migration. CM lowered the TNF-α and augmented the anti-inflammatory IL-10 levels in sera and exudates of arthritic rats. It also attenuated the expression of activated NF-κBp65, COX-2 and iNOS in the lining of the dorsal pouch. Notably, CM inhibited the MAPK pathway signal transduction via lowering the phosphorylation of p38 MAPK, ERK1/2 and JNK1/2 in rat hind paws. Additionally, CM administration lowered the lipid peroxide and nitric oxide levels and boosted glutathione and total anti-oxidant capacity in sera and exudates of animals. Conclusion: The observed CM downregulation of the arthritic process may support the interest of CM consumption as an adjunct approach for the management of RA.

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