In vivo anti‐inflammatory activity of Fabaceae species extracts screened by a new ex vivo assay using human whole blood

Introduction: Pain is an immunological response to any infection or inflammation and long term use of pain management therapy includes use of Nonsteroidal anti-inflammatory drugs which is associated with occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods. Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds was carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effect along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti-nociceptive and anti-inflammatory effect along with cytotoxic activity and certain modification in structure may result in potent activity.

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Naringenin has anti-inflammatory properties in macrophage and ex vivo human whole-blood models

Journal of Periodontal Research ◽

10.1111/j.1600-0765.2007.01055.x ◽

2008 ◽

Vol 43 (4) ◽

pp. 400-407 ◽

Cited By ~ 78

Author(s):

C. Bodet ◽

V. D. La ◽

F. Epifano ◽

D. Grenier

Keyword(s):

Whole Blood ◽

Ex Vivo ◽

Human Whole Blood ◽

Anti Inflammatory

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Sorbaria kirilowii Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB

Biomolecules ◽

10.3390/biom10050741 ◽

2020 ◽

Vol 10 (5) ◽

pp. 741 ◽

Cited By ~ 1

Author(s):

Jiwon Jang ◽

Jong Sub Lee ◽

Young-Jin Jang ◽

Eui Su Choung ◽

Wan Yi Li ◽

...

Keyword(s):

Signaling Pathways ◽

Ex Vivo ◽

Ethanol Extract ◽

Inflammatory Activity ◽

No Production ◽

Nuclear Factor ◽

Anti Inflammatory ◽

Inflammatory Effect

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.

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Ex Vivo and In Vivo Evidence of Anti-Inflammatory Activity of P-aminophenol and Salicylate Derivatives

Current Bioactive Compounds ◽

10.2174/1573407215666190211150700 ◽

2020 ◽

Vol 16 (5) ◽

pp. 593-605

Author(s):

André F. Vilvert ◽

Marcus Vinícius P.S. Nascimento ◽

Rosivaldo dos S. Borges ◽

Eduardo M. Dalmarco

Keyword(s):

Nitric Oxide ◽

Interleukin 6 ◽

Ex Vivo ◽

Inflammatory Activity ◽

Potential Candidate ◽

Antiinflammatory Drugs ◽

Gentisic Acid ◽

Anti Inflammatory ◽

Inflammatory Effect

Background: Paracetamol (p-aminophenol) and salicylates are nonsteroidal antiinflammatory drugs that are widely used in the general population. The adverse effects of both drugs continue to be a focus of the pharmaceutical industry in the development of new molecules that will increase treatment safety. In this context, we tested nine compounds derived from paracetamol and salicylates, synthesized in our laboratory, for their safety and ex vivo and in vivo anti-inflammatory activity. Methods: We analyzed the cytotoxicity of the compounds in ex vivo mice neutrophils, and their ability to inhibit the production of pro-inflammatory mediators (nitric oxide and interleukin-6) after stimulating with LPS. Next, in the selected molecules, we evaluated the anti-inflammatory effect on an in vivo inflammatory model of acute lung injury in mice. All nine compounds were also submitted to the cytotoxicity assay, like the original compounds. Results: None of the compounds showed cytotoxicity under the cells used. However, of the initial compounds, only five demonstrated anti-inflammatory effect, inhibiting Nitric Oxide (NO) and interleukin 6 (IL-6) production by neutrophils stimulated with Lipopolysaccharide (LPS). After this initial trial, four modified compounds were able to reduce leukocyte migration and fluid leakage in the bronchoalveolar lavage of mice. However, only the compound 5a1, derived from the esterification of gentisic acid, was able to significantly inhibit the levels of all pro-inflammatory cytokines and increase the levels of antiinflammatory cytokines evaluated. Conclusion: In conclusion, all compounds showed a good safety profile, and many of them had an antiinflammatory effect. However, the compound derived from gentisic acid is highlighted for its significant effects ex vivo and in vivo and in this context, we believe that this compound is a potential candidate for the development of a new anti-inflammatory drug.

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LIPID NANOPARTICLES FOR TRANSDERMAL DELIVERY OF CELECOXIB: AN IN VITRO AND IN VIVO INVESTIGATION

INDIAN DRUGS ◽

10.53879/id.56.08.11694 ◽

2019 ◽

Vol 56 (08) ◽

pp. 38-48

Author(s):

S. V Shinde ◽

S Nikam ◽

P Raut ◽

M. K. Ghag ◽

Keyword(s):

Solid Lipid Nanoparticles ◽

Ex Vivo ◽

Research Work ◽

Lipid Nanoparticles ◽

Inflammatory Activity ◽

Promising Alternative ◽

Solid Lipid ◽

Anti Inflammatory

In the present research work, celecoxib (CXB) loaded solid lipid nanoparticles (SLNs) were prepared using the probe sonication method, wherein Glyceryl monostearate and Tween 80 were used as solid lipid and surfactant, respectively. To obtain the statistically optimized batch, 32 factorial design was applied. The optimized batch was characterized physicochemically and evaluated through DSC, SEM and XRD studies. The mean particle size of the optimized batch was found to be 135.41± 0.24 nm with a mean % entrapment efficiency of 80 ± 1.69%. The optimized batch was further lyophilized and dispersed into 1% w/v Carbopol 934P to form a gel. Prepared gel was further evaluated for in vitro drug release, occlusivity, ex vivo permeability, local toxicity, in vivo anti-inflammatory activity and accelerated stability study. The study resulted in stable, safe and prolonged anti-inflammatory activity with quick onset of action. Hence, celecoxib loaded solid lipid nanoparticles can be considered as promising alternative to conventional topical systems.

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Preliminary Assessment of the Anti-Inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

Molecules ◽

10.3390/molecules26216630 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6630

Author(s):

Daria D. Vaulina ◽

Kira I. Stosman ◽

Konstantin V. Sivak ◽

Andrey G. Aleksandrov ◽

Nikolai B. Viktorov ◽

...

Keyword(s):

Ex Vivo ◽

Inflammatory Activity ◽

Preliminary Evaluation ◽

Moderate Increase ◽

Biodistribution Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

The Brain

Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [11C]MPbP (4′-[11С]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [18F]F-IV in a rodent model of neuroinflammation. [18F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by 18F-fluoroethylation of the precursor with Boc-protecting group (15) with [18F]2-fluoro-1-bromoethane ([18F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [18F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [11C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.

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In Vivo Acute Anti-Inflammatory Activity of Essential Oils: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211123091541 ◽

2021 ◽

Vol 21 ◽

Author(s):

Letícia Groli Lucca ◽

Pedro Roosevelt Torres Romão ◽

Márcia Vignoli-Silva ◽

Valdir F. da Veiga-Junior ◽

Letícia S. Koester

Keyword(s):

Essential Oils ◽

Inflammatory Mediators ◽

Ex Vivo ◽

Experimental Models ◽

New Drugs ◽

Inflammatory Activity ◽

Paw Edema ◽

Anti Inflammatory

: In recent years, there was a significant increase in the search for new therapeutic strategies for the treatment of inflammatory diseases. In this sense, natural products emerge as a potential source for the discovery of new drugs, with the research of the pharmacological properties of these products being very important. In addition to its function in plants (insect attraction and repellency), essential oils present pharmacological effects, such as antibacterial, antifungal, antimutagenic, antiviral, antiprotozoal, antioxidant, antidiabetic and anti-inflammatory properties. In this review, we describe the mostly used in vivo acute inflammatory experimental models and the studies showing the in vivo anti-inflammatory activity of essential oils. Essential oil from species from the Apiaceae, Asteraceae, Burseraceae, Boraginaceae, Cupressaceae, Euphorbiaceae, Fabaceae, Lamiaceae, Lauraceae, Myrtaceae, Piperaceae, Poaceae, Rutaceae, Verbenaceae and Zingiberaceae families were described as being anti-inflammatory in vivo. Five models of acute inflammation are commonly used to investigate the anti-inflammatory activity in vivo: ear and paw edema, pleurisy, peritonitis and the subcutaneous air pouch model. In addition to in vivo analysis, ex vivo and in vitro experiments are carried out to study the anti-inflammatory action of essential oils. The most commonly used model was paw edema, especially due to this model being easy to perform. In order to suggest or elucidate the mechanisms involved in the anti-inflammatory effect, many studies measured some inflammatory mediators such as cytokines, COX-2 expression and the levels of PGE2, and NO, or evaluated the effect of essential oils or their major compounds on inflammation response directly induced by inflammatory mediators.

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CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity

Stem Cells International ◽

10.1155/2019/8717694 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Kezhe Tan ◽

Hongtao Zhu ◽

Jianfang Zhang ◽

Weili Ouyang ◽

Jianfeng Tang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ex Vivo ◽

Inflammatory Activity ◽

Cell Based Therapy ◽

Pericardial Adipose Tissue ◽

Anti Inflammatory ◽

Cd73 Expression ◽

Cultivation In Vitro

Mesenchymal stem cells (MSC) are not universal and may be subject to dynamic changes upon local milieus in vivo and after isolation and cultivation in vitro. Here, we demonstrate that MSC derived from murine pericardial adipose tissue (pMSC) constitute two cohorts of population distinguished by the level of CD73 expression (termed as CD73high and CD73low pMSC). Transplantation of two types of cells into mouse hearts after myocardial infarction (MI) revealed that the CD73high pMSC preferentially brought about structural and functional repair in comparison to the PBS control and CD73low pMSC. Furthermore, the CD73high pMSC displayed a pronounced anti-inflammatory activity by attenuating CCR2+ macrophage infiltration and upregulating several anti-inflammatory genes 5 days after in vivo transplantation and ex vivo cocultivation with peritoneal macrophages. The immunomodulatory effect was not seen in cocultivation experiments with pMSC derived from CD73 knockout mice (CD73-/-) but was partially blocked by pretreatment of the A2b receptor antagonist, PSB603. The results highlight a heterogeneity of the CD73 expression that may be related to its catalytic products on the modulation of the local immune response and thus provide a possible explanation to the inconsistency of the regenerative results when different sources of donor cells were used in stem cell-based therapy.

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A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649213 ◽

1977 ◽

Vol 37 (01) ◽

pp. 154-161 ◽

Cited By ~ 1

Author(s):

B. A Janik ◽

S. E Papaioannou

Keyword(s):

Side Effects ◽

Effective Dose ◽

Fibrinolytic Activity ◽

Ex Vivo ◽

Plasminogen Activators ◽

Assay System ◽

Coagulation Parameters ◽

Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

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Adenosine Diphosphate (ADP)-Induced ⍺-Granules Release from Platelets of Native Whole Blood Is Reduced by Ticlopidine but Not by Aspirin or Dipyridamole

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661629 ◽

1986 ◽

Vol 56 (02) ◽

pp. 147-150 ◽

Cited By ~ 18

Author(s):

V Pengo ◽

M Boschello ◽

A Marzari ◽

M Baca ◽

L Schivazappa ◽

...

Keyword(s):

Whole Blood ◽

Light Transmission ◽

Ex Vivo ◽

Early Stage ◽

Shape Change ◽

Adenosine Diphosphate ◽

Dose Dependent ◽

Plateletderived Growth Factor ◽

Platelet Shape

SummaryA brief contact between native whole blood and ADP promotes a dose-dependent release of platelet a-granules without a fall in the platelet number. We assessed the “ex vivo” effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the a-granules release for an ADP stimulation of 0.4 (p <0.02), 1.2 (p <0.01) and 2 pM (p <0.01). No drug, however, completeley inhibits this early stage of platelet activation. The platelet release of α-granules may be related to platelet shape change of the light transmission aggregometer and may be important “in vivo” by enhancing platelet adhesiveness and by liberating the plateletderived growth factor.

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