scholarly journals Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4733
Author(s):  
Kiran Reddi ◽  
Hanxuan Li ◽  
Wei Li ◽  
Sarada Tetali
Keyword(s):  
Arachidonic Acid ◽  
Molecular Modeling ◽  
Direct Interaction ◽  
Ligand Binding Site ◽  
Quantitative Real Time Pcr ◽  
Tnf Α ◽  
Molecular Modeling Studies ◽  
Therapeutic Properties ◽  
Cox 2 ◽  
Activated Monocytes

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.

2‐Mercapto Benzthiazole Coupled Benzyl Triazoles as New COX‐2 Inhibitors: Design, Synthesis, Biological Testing and Molecular Modeling Studies

2019 ◽  
Vol 4 (37) ◽  
pp. 11081-11092
Author(s):  
Satyanarayana Yatam ◽  
Surender Singh Jadav ◽  
Krishna Prasadh Gundla ◽  
Kalyani Paidikondala ◽  
Ashok Reddy Ankireddy ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Biological Testing ◽  
Design Synthesis ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Cox 2 ◽  
Cox 2 Inhibitors

scholarly journals The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-κB Activation

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2855 ◽  
Author(s):  
Sara Carpi ◽  
Egeria Scoditti ◽  
Marika Massaro ◽  
Beatrice Polini ◽  
Clementina Manera ◽  
...  
Keyword(s):  
Olive Oil ◽  
Inflammatory Diseases ◽  
Virgin Olive Oil ◽  
Direct Interaction ◽  
Extra Virgin Olive Oil ◽  
Computational Studies ◽  
Related Gene ◽  
Expression Of Genes ◽  
Tnf Α ◽  
Cox 2

Inflammation of the adipose tissue plays an important role in the development of several chronic diseases associated with obesity. Polyphenols of extra virgin olive oil (EVOO), such as the secoiridoids oleocanthal (OC) and oleacein (OA), have many nutraceutical proprieties. However, their roles in obesity-associated adipocyte inflammation, the NF-κB pathway and related sub-networks have not been fully elucidated. Here, we investigated impact of OC and OA on the activation of NF-κB and the expression of molecules associated with inflammatory and dysmetabolic responses. To this aim, fully differentiated Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were pre-treated with OC or OA before stimulation with TNF-α. EVOO polyphenols significantly reduced the expression of genes implicated in adipocyte inflammation (IL-1β, COX-2), angiogenesis (VEGF/KDR, MMP-2), oxidative stress (NADPH oxidase), antioxidant enzymes (SOD and GPX), leukocytes chemotaxis and infiltration (MCP-1, CXCL-10, MCS-F), and improved the expression of the anti-inflammatory/metabolic effector PPARγ. Accordingly, miR-155-5p, miR-34a-5p and let-7c-5p, tightly connected with the NF-κB pathway, were deregulated by TNF-α in both cells and exosomes. The miRNA modulation and NF-κB activation by TNF-α was significantly counteracted by EVOO polyphenols. Computational studies suggested a potential direct interaction between OC and NF-κB at the basis of its activity. This study demonstrates that OC and OA counteract adipocyte inflammation attenuating NF-κB activation. Therefore, these compounds could be novel dietary tools for the prevention of inflammatory diseases associated with obesity.

scholarly journals Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 661 ◽  
Author(s):  
Venugopala ◽  
Al-Attraqchi ◽  
Tratrat ◽  
Nayak ◽  
Morsy ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Therapeutic Agents ◽  
Cox Inhibitors ◽  
Lead Compounds ◽  
Important Target ◽  
Pharmacokinetic Properties ◽  
Molecular Modeling Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity. Compound 4e was identified as the most active compound of the series with an IC50 of 6.71 M, which is comparable to the IC50 of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID). Molecular modeling and crystallographic studies were conducted to further characterize the compounds and gain better understanding of the binding interactions between the compounds and the residues at the active site of the COX-2 enzyme. The pharmacokinetic properties and potential toxic effects were predicted for all the synthesized compounds, which indicated good drug-like properties. Thus, these synthesized compounds can be considered as potential lead compounds for developing effective anti-inflammatory therapeutic agents.

New Coumarin Derivatives as Potent Selective COX-2 Inhibitors: Synthesis, Anti-Inflammatory, QSAR, and Molecular Modeling Studies

2015 ◽  
Vol 348 (12) ◽  
pp. 875-888 ◽  
Author(s):  
Dina H. Dawood ◽  
Rasha Z. Batran ◽  
Thoraya A. Farghaly ◽  
Mohammed A. Khedr ◽  
Mohamed M. Abdulla
Keyword(s):  
Molecular Modeling ◽  
Coumarin Derivatives ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

DESIGN OF POTENTIAL CYCLOOXYGENASE INHIBITORS USING PHARMACOPHORE OPTIMIZATION BY MOLECULAR MODELING STUDIES

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (12) ◽  
pp. 16-22
Author(s):  
S. S Todkar ◽  
◽  
A. H. Hoshmani
Keyword(s):  
Molecular Modeling ◽  
Nearest Neighbor ◽  
3D Qsar ◽  
Field Analysis ◽  
K Nearest Neighbor ◽  
Qsar Studies ◽  
2D Qsar ◽  
Molecular Modeling Studies ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Recently discovery of relation between cyclooxygenase–2 (COX–2) inhibition and prevention of growth of cansar cells is a major area for research in medicinal chemistry, as it is free from side effects which are genetically shown by developed anticancer agents. In an attempt to develop potent and nontoxic COX–2 inhibitors, we have optimized the 1,5- diaryl pyrazole pharmacophore by using molecular modeling studies. In this paper we present results of 2D and 3D QSAR studies of a series of 22 molecules containing 1,5- diaryl pyrazole pharmacophore as selective COX–2 inhibitors. The 3D QSAR studies were performed using two different methods, stepwise variable selection k–nearest neighbor molecular field analysis (SW kNN–MFA) and simulated annealing k–nearest neighbor molecular field analysis (SA kNN–MFA) methods. The 2D QSAR studies were performed using multiple regressions. 3D QSAR studies produced reasonably good predictive models with high cross–validated r2cv value of 0.732 and 0.783 and predicted r2 value of 0.882 and 0.794 values using the models SW kNN–MFA and SA kNN–MFA method, respectively, whereas the r2 & predicted r2 value in 2D QSAR studies was found to be 0.84914 & 0.9157, respectively. the 2D QSAR studies indicated contribution of different physicochemical descriptors and the result of 3D QSAR studies indicated the exact steric and electronic requirement in the ranges at various positions in the 1,5- diaryl pyrazole pharmacophore. The pharmacophore requirement for selective COX–2 inhibition was optimized and requirement at various positions around 1, 5- diaryl pyrazole pharmacophore were defined.

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