The Biological Function Prediction of The 10-gingerol Compound of Ginger in Inhibiting Cyclooxygenase-2 Activity

Anti-inflammatory agents inhibit prostaglandin synthesis by blocking cyclooxygenases (COXs). The compounds extracted from ginger, 10-gingerol and 10-shogaol can inhibit inflammation but the mechanism of inhibition remains unclear. Here we used molecular docking to predict the molecular interactions between COXs and the three inhibitors, acetaminophen (CID1983), 10-gingerol (CID168115) and 10-shogaol (CID6442612). By using that acetaminophen as a gold standard, the results demonstrated that acetaminophen, 10-gingerol, and 10-shogaol could bind catalytic domain and membrane binding domain of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The 10-shogaol did not show significantly different binding energy to bind to COX-1 and COX-2. The 10-gingerol posed a stronger and more specific binding to the membrane-binding domain of COX-2 than acetaminophen and 10-shogaol. The specific binding of the 10-gingerol to COX-2 could prevent the binding of the natural substrate, arachidonic acid. The results provide useful information to improving activities of anti-inflammatory.

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Studi In Silico Senyawa Alkaloid Herba Bakung Putih (Crinum Asiaticum L.) pada Penghambatan Enzim Siklooksigenase (COX)

Jurnal Kimia VALENSI ◽

10.15408/jkv.v4i2.7686 ◽

2018 ◽

Vol 4 (2) ◽

pp. 124-136

Author(s):

Rizky Arcinthya Rachmania ◽

Hariyanti Hariyanti ◽

Ririh Zikriah ◽

Aditya Sultan

Keyword(s):

Molecular Docking ◽

Tissue Injury ◽

Protein Docking ◽

Enzyme Activation ◽

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Crinum Asiaticum ◽

Cox 1

Inflammation is a response to tissue injury involving the physiological process of cyclooxygenase enzyme activation which has two isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. The use of anti-inflammatory drugs of Non Steroidal Anti Inflammatory (AINS) and steroid groups has side effects in long-term use. The objective of this study was to find out eight active white herbic alkaloid compounds (Crinum asiaticum L.) to be used as anti-inflammatory by inhibiting COX-1 and COX-2 enzymes. Molecular docking method for the prediction of complex structures of proteins called ligand-protein docking using the PLANTS 1.2 software. where the lowest ChemPLP score which is free energy is the molecular tethering parameter. The herbaceous white herbaceae compound obtained the lowest CHEMPLP score of hippadine -83.3684 Kcal / mol and pratorimin -83.2661 Kcal / mol and aspirin comparator -67.3292 Kcal / mol and paracetamol -66.3535 Kcal / mol. Molecular docking in COX-2 shows lycobetaine -87.3991 Kcal / mol is lower than that of the celecoxib -85.3729 Kcal / mol comparator against the cyclooxygenase-2 receptor (COX-2). These results show that the white lycopene alkaloid compounds hyppadine, pratorimin and lycobetaine have better affinity and stability than the comparative compounds. The results of drug scans, hippadin, pratorimin and lycobetaine have the criteria for oral preparations. It can be concluded that herbaceous white herbaceae are predicted to have potential as anti-inflammatory compounds.

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Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection

Journal of Virology ◽

10.1128/jvi.00014-21 ◽

2021 ◽

Cited By ~ 1

Author(s):

Jennifer S. Chen ◽

Mia Madel Alfajaro ◽

Ryan D. Chow ◽

Jin Wei ◽

Renata B. Filler ◽

...

Keyword(s):

Immune Response ◽

Viral Replication ◽

Cyclooxygenase 2 ◽

Nsaid Treatment ◽

Susceptibility To Infection ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Abstract Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which mediate the production of prostaglandins (PGs). As PGs play diverse biological roles in homeostasis and inflammatory responses, inhibiting PG production with NSAIDs could affect COVID-19 pathogenesis in multiple ways, including: (1) altering susceptibility to infection by modifying expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2; (2) regulating replication of SARS-CoV-2 in host cells; and (3) modulating the immune response to SARS-CoV-2. Here, we investigate these potential roles. We demonstrate that SARS-CoV-2 infection upregulates COX-2 in diverse human cell culture and mouse systems. However, suppression of COX-2 by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication. In contrast, in a mouse model of SARS-CoV-2 infection, NSAID treatment reduced production of pro-inflammatory cytokines and impaired the humoral immune response to SARS-CoV-2 as demonstrated by reduced neutralizing antibody titers. Our findings indicate that NSAID treatment may influence COVID-19 outcomes by dampening the inflammatory response and production of protective antibodies rather than modifying susceptibility to infection or viral replication. Importance Public health officials have raised concerns about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating symptoms of coronavirus disease 2019 (COVID-19). NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are critical for the generation of prostaglandins – lipid molecules with diverse roles in homeostasis and inflammation. Inhibition of prostaglandin production by NSAIDs could therefore have multiple effects on COVID-19 pathogenesis. Here, we demonstrate that NSAID treatment reduced both the antibody and pro-inflammatory cytokine response to SARS-CoV-2 infection. The ability of NSAIDs to modulate the immune response to SARS-CoV-2 infection has important implications for COVID-19 pathogenesis in patients. Whether this occurs in humans and whether it is beneficial or detrimental to the host remains an important area of future investigation. This also raises the possibility that NSAIDs may alter the immune response to SARS-CoV-2 vaccination.

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Involvement of cyclooxygenase 2 (COX-2) in intrinsic tone of isolated guinea pig

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y95-215 ◽

1995 ◽

Vol 73 (11) ◽

pp. 1561-1567 ◽

Cited By ~ 21

Author(s):

L. Charette ◽

C. Misquitta ◽

J. Guay ◽

D. Riendeau ◽

T. R. Jones

Keyword(s):

Guinea Pig ◽

Time Course ◽

Cyclooxygenase 2 ◽

Maximal Response ◽

Pharmacological Agents ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Cox 2 Inhibitors ◽

Cox 1

Indomethacin and related nonsteroidal anti-inflammatory drugs relax prostanoid-dependent intrinsic tone of isolated guinea pig trachea by inhibiting cyclooxygenase (COX). Recently, a second isoform of COX (COX-2) was discovered, which differed from COX-1 with respect to protein structure, transcriptional regulation, and susceptibility to inhibition by pharmacological agents. It is now known that indomethacin nonselectively inhibits COX-1 and COX-2, whereas NS-398 is a selective inhibitor of COX-2. In the present study we compared the activity of a selective (NS-398) and nonselective (indomethacin) COX-2 inhibitor on intrinsic tone of isolated guinea pig trachea. NS-398 ≥ indomethacin produced a reversal of intrinsic tone with a similar concentration-dependent (10 nM to 1 μM) time course (Tmax approximately 20–45 min), potency (EC50 1.7 and 5.6 nM, respectively), and maximal response. Contractions to cholinergic nerve stimulation (45 V, 0.5 ms, 0.1–32 Hz) and histamine were similarly modulated in tissues relaxed with the selective or nonselective COX-2 inhibitors. Immunoblot analyses showed that COX-2 protein synthesis was induced in both the cartilage and smooth muscle portions of the trachea during changes in intrinsic tone. These findings are consistent with pharmacological results and provide the first demonstration that prostanoid tone in isolated guinea pig trachea is dependent on COX-2 activity. The results also suggest that the activity of indomethacin in this preparation is likely related to COX-2 inhibition.Key words: cyclooxygenase 2, relaxation, guinea pig trachea, cyclooxygenase 1.

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Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

Gastroenterology ◽

10.1016/s0016-5085(98)80332-6 ◽

1998 ◽

Vol 114 ◽

pp. A82

Author(s):

T. Brzozowski ◽

P.C. Konturek ◽

R. Pajdo ◽

N. Nagraba ◽

A. Szczeklik ◽

...

Keyword(s):

Cyclooxygenase 2 ◽

Mild Stress ◽

Adaptive Cytoprotection ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Cox 1

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ANTI-INFLAMMATORY ACTIVITY OF BACTERIA ASSOCIATED WITH MARINE SPONGE (HALICLONA AMBOINENSIS) VIA REDUCTING NO PRODUCTION AND INHIBITING CYCLOOXYGENASE-1, CYCLOOXYGENASE-2, AND SECRETORY PHOSPHOLIPASE A2 ACTIVITIES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.20094 ◽

2017 ◽

Vol 10 (11) ◽

pp. 95 ◽

Cited By ~ 1

Author(s):

Yosie Andriani ◽

Leni Marlina ◽

Habsah Mohamad ◽

Hermansyah Amir ◽

Siti Aisha M Radzi ◽

...

Keyword(s):

Methanol Extract ◽

Inflammatory Activity ◽

No Production ◽

Secretory Phospholipase A2 ◽

Phytochemical Screening ◽

Spla2 Activity ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Objective: This study aimed to investigate the anti-inflammatory activity of methanol extract and fractions of bacteria associated with sponge (Haliclona amboinensis) and to evaluate their effect in reducing NO production and inhibiting cyclooxygenase-1 (COX-1), cyclooxgenase-2 (COX-2) and secretory phospholipase A2 (sPLA2) activity.Methods: All bacterial isolates were cultured and supernatants were collected for the extraction of secondary metabolites using diaion HP-20 to obtain methanol extracts. Evaluation of cytotoxicity property was carried out on macrophage cell lines (RAW264.7) by 3-(4,5-dimethylthiazol- 2-yl) 2,5-diphenyl tetrazoliumbromide assay. Anti-inflammatory screening was done by inducible nitric oxide assay on RAW264.7 cell lines with lipopolysaccharide (LPS) stimulation. Dianion HP-20 was used to remove salt content. A selected methanol extract was subjected to further fractionations by C-18 reverse phase and their anti-inflammatory potential was evaluated by COX-1 and COX-2, and sPLA2 enzymatic assay.Results: Seven methanol extracts showed no cytotoxic property against RAW 264.7 cell line (inhibitory concentration 50% > 30 μg/ml) and selected for anti-inflammatory screening assay. Result showed methanol extract HM 1.2 reduced NO production >80% and it has been selected for phytochemical screening, further fractionations and assay. Phytochemical screening showed alkaloids and terpenoids present in the HM 1.2. The HM 1.2 and its fractions (F1, F2, F1C1, F1C2, F1C3, and F1C4) were proven to inhibit COX-1, COX-2, and sPLA2 activity in the range of 60.516-116.886%, 20.554- 116.457%, and 70.2667-114.8148%, respectively.Conclusions: This study revealed that bacteria associated with H. amboinensis have produced anti-inflammatory activity via reducing NO production and inhibiting COX-1, COX-2, and sPLA2 activity.

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Evaluation of Anti-Inflammatory Components of Guizhi Fuling Capsule, an Ancient Chinese Herbal Formula, in Human Umbilical Vein Endothelial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2029134 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yuzhong Zheng ◽

Guizhong Xin ◽

Guowei Gong ◽

Tina TX Dong ◽

Ping Li ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Active Components ◽

Human Umbilical Vein ◽

Cellular Inflammation ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Umbilical Vein Endothelial Cells ◽

Cox 1

Background. Guizhi Fuling capsule (GFC), a well-known formula composed of five medicinal herbs, is commonly prescribed to treat primary dysmenorrhea, as well as to achieve good clinical efficacy in China. However, the active components of GFC have not been identified. Here, the anti-inflammatory functions of GFC, as well as its major ingredients, were evaluated in human umbilical vein endothelial cells (HUVECs). Methods. Lipopolysaccharide (LPS) was used in HUVECs to imitate the cellular inflammation. Then, GFC-triggered mRNA expressions of cyclooxygenase-1 (COX-1) and COX-2 were determined by real-time PCR, while the expression of COX-2 protein was revealed by western blotting. Besides, nine components of GFC were evaluated for their contribution value in the anti-dysmenorrhea effects Results. The application of GFC downregulated the mRNA expressions of COX-1 and COX-2 mRNAs. Nine major components of GFC were tested in the inflammatory system, and three compounds, including paeoniflorin, benzoylpaeoniflorin, and amygdalin, exhibited robust activation in HUVECs. The combination of paeoniflorin, benzoylpaeoniflorin, and amygdalin showed over 80% of the anti-inflammatory activation. Conclusion. Our study supports that GFC plays a promising role in anti-dysmenorrhea function by decreasing COXs’ expression. Besides, paeoniflorin, benzoylpaeoniflorin, and amygdalin could be considered as major regulators for the anti-dysmenorrhea effects of GFC.

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Synthesis of Novel Benzodifuranyl; 1,3,5-Triazines; 1,3,5-Oxadiazepines; and Thiazolopyrimidines Derived from Visnaginone and Khellinone as Anti-Inflammatory and Analgesic Agents

Molecules ◽

10.3390/molecules25010220 ◽

2020 ◽

Vol 25 (1) ◽

pp. 220 ◽

Cited By ~ 6

Author(s):

Ameen Ali Abu-Hashem ◽

Sami A Al-Hussain ◽

Magdi E. A. Zaki

Keyword(s):

Sodium Ethoxide ◽

Standard Drug ◽

Chemical Structures ◽

Cyclooxygenase 1 ◽

Analgesic Agents ◽

Cox 2 ◽

Anti Inflammatory ◽

New Compounds ◽

Cox 2 Inhibitors ◽

Cox 1

Novel (4-methoxy or 4,8-dimethoxy)-3-methyl-N-(6-oxo-2-thioxo-1,2,3, 6-tetrahydro- pyrimidin-4-yl) benzo [1,2-b: 5, 4-b’] difuran-2-carboxamide (5a–b) has been synthesized by the reaction of visnagenone–ethylacetate (2a) or khellinone–ethylacetate (2b) with 6-aminothiouracil in dimethylformamide or refluxing of benzofuran-oxy-N-(2-thioxopyrimidine) acetamide (4a–b) in sodium ethoxide to give the same products (5a,b) in good yields. Thus, compounds 5a–b are used as an initiative to prepare many new heterocyclic compounds such as 2-(4-(3-methylbenzodifuran- 2-carbox-amido) pyrimidine) acetic acid (6a–b), N-(thiazolo[3, 2-a]pyrimidine)-3-methylbenzo- difuran-2-carboxamide (7a–b), N-(2-thioxopyrimidine)-methylbenzodifuran-2-carbimidoylchloride (8a–b), N-(2-(methyl-thio) pyrimidine)-3-methylbenzodifuran-2-carbimidoylchloride (9a–b), N-(2, 6 -di(piperazine or morpholine)pyrimidine)-1-(3-methylbenzodifuran)-1-(piperazine or morpholine) methanimine(10a–d), 8-(methylbenzodifuran)-thiazolopyrimido[1,6-a][1,3,5]triazine-3,5-dione (11a –b), 8-(3-methyl benzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-trione (12a–b), and 2,10 -di(sub-benzylidene)-8-(3-methylbenzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-3,5,11- trione (13a–f). All new chemical structures were illustrated on the basis of elemental and spectral analysis (IR, NMR, and MS). The new compounds were screened as cyclooxygenase-1/ cyclooxygenase-2 (COX-1/COX-2) inhibitors and had analgesic and anti-inflammatory activities. The compounds 10a–d and 13a–f had the highest inhibitory activity on COX-2 selectivity, with indices of 99–90, analgesic activity of 51–42% protection, and anti-inflammatory activity of 68%–59%. The inhibition of edema for the same compounds, 10a–d and 13a–f, was compared with sodium diclofenac as a standard drug.

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