scholarly journals The Compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01): A Potential Drug for Treatment of Inflammatory Diseases

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 188
Author(s):  
Pablo Rayff da Silva ◽  
Renan Fernandes do Espírito Santo ◽  
Camila de Oliveira Melo ◽  
Fábio Emanuel Pachú Cavalcante ◽  
Thássia Borges Costa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inflammatory Diseases ◽  
Molecular Targets ◽  
In Vitro Assays ◽  
Potential Drug ◽  
Paw Edema ◽  
Crystallographic Structures ◽  
Cox 2

The compound (E)-2-cyano-N,3-diphenylacrylamide (JMPR-01) was structurally developed using bioisosteric modifications of a hybrid prototype as formed from fragments of indomethacin and paracetamol. Initially, in vitro assays were performed to determine cell viability (in macrophage cultures), and its ability to modulate the synthesis of nitrite and cytokines (IL-1β and TNFα) in non-cytotoxic concentrations. In vivo, anti-inflammatory activity was explored using the CFA-induced paw edema and zymosan-induced peritonitis models. To investigate possible molecular targets, molecular docking was performed with the following crystallographic structures: LT-A4-H, PDE4B, COX-2, 5-LOX, and iNOS. As results, we observed a significant reduction in the production of nitrite and IL-1β at all concentrations used, and also for TNFα with JMPR-01 at 50 and 25 μM. The anti-edematogenic activity of JMPR-01 (100 mg/kg) was significant, reducing edema at 2–6 h, similar to the dexamethasone control. In induced peritonitis, JMPR-01 reduced leukocyte migration by 61.8, 68.5, and 90.5% at respective doses of 5, 10, and 50 mg/kg. In silico, JMPR-01 presented satisfactory coupling; mainly with LT-A4-H, PDE4B, and iNOS. These preliminary results demonstrate the strong potential of JMPR-01 to become a drug for the treatment of inflammatory diseases.

scholarly journals Anti-Inflammatory Activities of Leaf Oil from Cinnamomum subavenium In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Xincai Hao ◽  
Weiguang Sun ◽  
Changbin Ke ◽  
Fuqian Wang ◽  
Yongbo Xue ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Chemical Constituents ◽  
Folk Medicine ◽  
Scientific Basis ◽  
Paw Edema ◽  
Leaf Oil ◽  
Cox 2 ◽  
Anti Inflammatory

The study determined the chemical constituents and anti-inflammatory effects of leaf oil from Cinnamomum subavenium (CS-LO) that has been used in folk medicine to treat various symptoms including inflammation. The anti-inflammatory effects of the oil were evaluated by LPS-stimulated RAW264.7 cells and the Carr-induced hind mouse paw edema model, respectively. In vitro, nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-6, and IL-1β were significantly decreased by CS-LO, and the expression of nuclear factor-κB (NF-κB) protein was blocked as well. In in vivo, the malondialdehyde (MDA) and paw edema levels were decreased by CS-LO, and the same result came up on the NO and tumor necrosis factor (TNF-a) of serum at the 5th h after Carr injection. In addition, iNOS and COX-2 immunoreactive cells of the paw tissue were decreased significantly by CS-LO (200 mg/kg) in histological examination. The present findings indicated that CS-LO have anti-inflammatory properties, and the effects might be caused through inhibiting iNOS, COX-2, TNF-α, IL-1β, and IL-6 expression via affecting NF-κB pathway, which will provide a power scientific basis for CS-LO to be used as the treatment of inflammatory diseases.

Drops of Lactiplantibacillus plantarum CRL 759 culture supernatant attenuates eyes inflammation induced by lipopolysaccharide

2021 ◽  
pp. 1-12
Author(s):  
B.I. Layús ◽  
M.A. Gomez ◽  
S.I. Cazorla ◽  
A.V. Rodriguez
Keyword(s):  
Inflammatory Diseases ◽  
Clinical Signs ◽  
Thiobarbituric Acid ◽  
Clinical Score ◽  
Ocular Inflammation ◽  
Retinal Cell ◽  
In Vitro Assays ◽  
Necrosis Factor Alpha

Anti-inflammatory effect of soluble secreted compounds of probiotic bacteria was widely demonstrated as therapy for different inflammatory diseases, but was not investigated in inflammatory eye disorders. The aim of this study was to determine whether Lactiplantibacillus plantarum CRL759 cell-free supernatant reduced inflammatory parameters and clinical signs in ocular inflammations. First, we evaluated the effect of L. plantarum CRL759 supernatant in vitro on human retinal cell line, ARPE-19 cells, stimulated with lipopolysaccharide (LPS). Then, we investigated in vivo its capacity to decrease inflammation by local administration on the eyes of mice with endotoxin induced inflammation. In vitro assays demonstrated that L. plantarum CRL759 supernatant reduced the production of interleukin (IL)-6, IL-8, nitric oxide and thiobarbituric acid reactive substances in LPS-stimulated ARPE-19 cells. Our in vivo data proved that L. plantarum supernatant significantly reduced the clinical score of endotoxin treated mice and diminished levels of tumour necrosis factor alpha, interferon gamma and protein concentration in aqueous humour. Histological examination showed reduction of infiltrating inflammatory cells in the posterior segment of the eyes. As far as we know, this is the first report showing that Lactobacillus spp. supernatant administered as drops reduces some parameters of ocular inflammation. This promising strategy is safe and could alleviate symptoms and signs of ocular inflammation in people that are refractories to the conventional therapies.

scholarly journals MESUAFERRIN A-BIOACTIVE FLAVONOID ISOLATED FROM THE BARK OF MESUA FERREA L. AGAINST PHOSPHOLIPASE A2, CYCLOOXYGENASE AND LIPOXYGENASE: AN IN VITRO, IN VIVO AND IN SILICO APPROACH

2018 ◽  
Vol 10 (2) ◽  
pp. 102
Author(s):  
Krishna Chaithanya K. ◽  
Gopalakrishnan V. K. ◽  
Zenebe Hagos ◽  
Govinda Rao D.
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Late Phase ◽  
Paw Edema ◽  
Dual Inhibitor ◽  
Metabolizing Enzymes ◽  
In Silico Studies ◽  
Cox 2

Objective: The main objective of the present study was to evaluate the anti-inflammatory activity of isolated bioactive flavonoid Mesuaferrin-A from the bark of Mesuaferrea L. by in vitro, in vivo and in silico approach.Methods: To evaluate the effect of isolated bioactive flavonoid Mesuaferrin-A on arachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) using in vitro methods, followed by carrageenan-induced paw edema model by in vivo and to determine the binding orientation and interactions of Mesuaferrin-A onarachidonic acid metabolizing enzymes (PLA2, COX-2 and 5-LOX) crystal proteins using molecular docking (in silico) studies.Results: Mesuaferrin-A exhibited a dose-dependent significant 5-LOX inhibitory and considerable COX-2 inhibitory activity by in vitro, The inhibitory activities of 5-LOX and COX-2 at 100µg/ml were found to be 78.67%, 81.03% with IC50 values of 45.22µg/ml and 35.74µg/ml respectively. Whereas Mesuaferrin-A showed less PLA2 inhibitory activity. Mesuaferrin-A showed 68.34% inhibitory activity at 400 mg/kg body weight at the late phase of carrageenan-induced paw edema, and In silico studies demonstrated that Mesuaferrin-A strongly binds with 5-LOX and COX-2, these strong binding affinity of Mesuaferrin-A on active site amino acids of 5-LOX and COX-2 may be responsible for inhibition of enzyme activity. Mesuaferrin-A showeda comparable 5-LOX and COX-2 inhibition activity with (positive control).Conclusion: It was concluded that Mesuaferrin-A act as 5-LOX and COX dual inhibitor, from the results it was suggests that Mesuaferrin-A, may be an effective preventive and therapeutic approach for patients with inflammatory-related diseases.

scholarly journals (E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

2020 ◽  
Vol 21 (7) ◽  
pp. 2591
Author(s):  
Pablo Silva ◽  
Maria de Almeida ◽  
Jamire Silva ◽  
Sonaly Albino ◽  
Renan Espírito-Santo ◽  
...  
Keyword(s):  
Condensation Reaction ◽  
Significant Inhibition ◽  
In Vitro Assays ◽  
Paw Edema ◽  
Substituted Anilines ◽  
Hybrid Compound ◽  
Design Synthesis ◽  
Anti Inflammatory

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1β and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg−1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2–6 h. In addition, there was no significant inhibition of PGE2, IL-1β or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.

scholarly journals Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory ResponseIn VitroandIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-19 ◽  
Author(s):  
Ji Young Cha ◽  
Ji Yun Jung ◽  
Jae Yup Jung ◽  
Jong Rok Lee ◽  
Il Je Cho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Herbal Formula ◽  
Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory

Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α)) and nuclear factor-kappa B (NF-κB) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-κB, and MAPKs as well as production of prostaglandin E2(PGE2), nitric oxide (NO), IL-6, and TNF-αinduced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-α. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWSin vitroandin vivo.

scholarly journals Pleiotropic mechanisms facilitated by resveratrol and its metabolites

2010 ◽  
Vol 429 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Barbara Calamini ◽  
Kiira Ratia ◽  
Michael G. Malkowski ◽  
Muriel Cuendet ◽  
John M. Pezzuto ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Molecular Targets ◽  
Quinone Reductase ◽  
Sirtuin 1 ◽  
Direct Result ◽  
Promote Cell Survival ◽  
Cox 2 ◽  
Cox 1

Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD+-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensively metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4′-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4′-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo an interplay between resveratrol and its metabolites with different molecular targets may be responsible for the overall beneficial health effects previously attributed only to resveratrol itself.

scholarly journals Evaluation of cannabidiol’s inhibitory effect on alpha-glucosidase and its stability in simulated gastric and intestinal fluids

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Hang Ma ◽  
Huifang Li ◽  
Chang Liu ◽  
Navindra P. Seeram
Keyword(s):  
Molecular Docking ◽  
High Performance ◽  
Inhibitory Effect ◽  
In Vitro Assays ◽  
Inhibitory Effects ◽  
In Vivo Models ◽  
Glucosidase Activity ◽  
Intestinal Fluids

Abstract Objective Cannabidiol (CBD) has been reported to have anti-diabetic effects in pre-clinical and clinical studies but its inhibitory effects on α-glucosidase, a carbohydrate hydrolyzing enzyme, remain unknown. Herein, we evaluated CBD’s inhibitory effects on α-glucosidase using in vitro assays and computational studies. Methods CBD’s inhibitory effect on α-glucosidase activity was evaluated in a yeast enzymatic assay and by molecular docking. The stability of CBD in simulated gastric and intestinal fluids was evaluated by high-performance liquid chromatography analyses. Results CBD, at 10, 19, 38, 76, 152, 304, 608, and 1216 μM, inhibited α-glucosidase activity with inhibition of 17.1, 20.4, 48.1, 56.6, 59.1, 63.7, 74.1, and 95.4%, respectively. Acarbose, the positive control, showed a comparable inhibitory activity (with 85.1% inhibition at 608 μM). CBD’s inhibitory effect on α-glucosidase was supported by molecular docking showing binding energy (-6.39 kcal/mol) and interactions between CBD and the α-glucosidase protein. CBD was stable in simulated gastric and intestinal fluids for two hours (maintained ≥ 90.0%). Conclusions CBD showed moderate inhibitory effect against yeast α-glucosidase activity and was stable in gastric and intestinal fluids. However, further studies on CBD’s anti-α-glucosidase effects using cellular and in vivo models are warranted to support its potential application for the management of type II diabetes mellitus.

scholarly journals Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 825
Author(s):  
Mohammad Khalid ◽  
Mohammed H. Alqarni ◽  
Ambreen Shoaib ◽  
Muhammad Arif ◽  
Ahmed I. Foudah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Arthritis Score ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

scholarly journals Benzophenone Derivatives Showed Dual Anti-Inflammatory and Antiproliferative Activities by Inhibiting COX Enzymes and Promote Cyclin E Downregulation

2022 ◽  
Author(s):  
Laís Folquitto ◽  
Thiago de Souza ◽  
Jaqueline Januario ◽  
Isadora Nascimento ◽  
Brenda Brandão ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Antiproliferative Activities ◽  
Mcf 7

Considering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo antiinflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7) showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA‑MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

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