scholarly journals Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19

2021 ◽  
Author(s):  
Jordana Grazziela A. Coelho dos Reis ◽  
Geovane Marques Ferreira ◽  
Alice Aparecida Lourenco ◽  
Agata Lopes Ribeiro ◽  
Camila Pacheco da Silveira Martins da Mata ◽  
...  
Keyword(s):  
Critically Ill ◽  
Ex Vivo ◽  
Tracheal Aspirate ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Cytokine Storm ◽  
Next Of Kin ◽  
Anti Inflammatory ◽  
Inflammatory Effect ◽  
Tracheal Aspirates

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic, antiviral, and anti-inflammatory effect of BromAc in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Method: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine storm analysis was performed. Results: BromAc displayed a robust mucolytic effect in a dose dependent manner. BromAc showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1RA and total reduction for IL-9 compared to NAC alone and control. BromAc acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250ug. Conclusion: These results indicate robust mucolytic and anti-inflammatory effect of BromAc in tracheal aspirates from critically ill COVID-19 patients, indicating its potential as a therapeutic strategy to COVID-19.

Anti-nociceptive and anti-inflammatory activity of synthesized novel benzoxazole derivatives

2021 ◽  
Vol 20 ◽  
Author(s):  
Mansi L. Patil ◽  
Swati S. Gaikwad ◽  
Naresh J. Gaikwad
Keyword(s):  
Cytotoxic Activity ◽  
Research Study ◽  
Ex Vivo ◽  
Immunological Response ◽  
Inflammatory Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Effect

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.

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

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 741 ◽  
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.

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

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.

scholarly journals Acute and Chronic Anti-inflammatory effect of Bryophyllum pinnatum Leaf Extract on Wistar Rats

2021 ◽  
pp. 6-14
Author(s):  
Emmanuel Ikechukwu Onwubuya ◽  
Henrietta Aritetsoma Ogbunugafor ◽  
Chike Samuel Okafor ◽  
Afees Adebayo Oladejo
Keyword(s):  
Bioactive Compounds ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Flame Ionization ◽  
Cotton Pellet ◽  
Anti Inflammatory ◽  
Inflammatory Effect ◽  
Bryophyllum Pinnatum

Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is used traditionally to treat many ailments. This study investigated the anti-inflammatory effect of hydro-ethanol leaf extract of Bryophyllum pinnatum on Wistar rats using acute and chronic models and also evaluates the bioactive compounds of the leaf extract. The phytochemical constituents of the plant extract were quantitatively determined by Gas Chromatography-Flame Ionization Detector (GC-FID) and acute anti-inflammatory activity was carried out with the aid of plethysmometer while chronic anti-inflammatory activity was investigated using cotton pellet. Results showed that the leaf extract of B. pinnatum was rich in kaempferol (7.006 ±0.02 μg/g), sapogenin (3.372 ±0.02 μg/g), rutin (1.837 ±0.01 μg/g) and lunamarine (1.359 ±0.01 μg/g). The findings showed that the plant had considerable anti-inflammatory effects in a dose dependent manner, returning edema in carragenean-induced and cotton pellet induced granuloma in Wistar rats to normal within 120 minutes and 7 days respectively. The findings of this work have shown that the leaf of B. pinnatum was rich in bioactive compounds which could be synthesized to produce new plant based product to fight inflammatory disorders with fewer side effects.

scholarly journals Computational Identification of Potential Anti-Inflammatory Natural Compounds Targeting the p38 Mitogen-Activated Protein Kinase (MAPK): Implications for COVID-19-Induced Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 653
Author(s):  
Seth O. Asiedu ◽  
Samuel K. Kwofie ◽  
Emmanuel Broni ◽  
Michael D. Wilson
Keyword(s):  
Molecular Docking ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Binding Energies ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Activity ◽  
Computational Techniques ◽  
Cytokine Storm ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Severely ill coronavirus disease 2019 (COVID-19) patients show elevated concentrations of pro-inflammatory cytokines, a situation commonly known as a cytokine storm. The p38 MAPK receptor is considered a plausible therapeutic target because of its involvement in the platelet activation processes leading to inflammation. This study aimed to identify potential natural product-derived inhibitory molecules against the p38α MAPK receptor to mitigate the eliciting of pro-inflammatory cytokines using computational techniques. The 3D X-ray structure of the receptor with PDB ID 3ZS5 was energy minimized using GROMACS and used for molecular docking via AutoDock Vina. The molecular docking was validated with an acceptable area under the curve (AUC) of 0.704, which was computed from the receiver operating characteristic (ROC) curve. A compendium of 38,271 natural products originating from Africa and China together with eleven known p38 MAPK inhibitors were screened against the receptor. Four potential lead compounds ZINC1691180, ZINC5519433, ZINC4520996 and ZINC5733756 were identified. The compounds formed strong intermolecular bonds with critical residues Val38, Ala51, Lys53, Thr106, Leu108, Met109 and Phe169. Additionally, they exhibited appreciably low binding energies which were corroborated via molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The compounds were also predicted to have plausible pharmacological profiles with insignificant toxicity. The molecules were also predicted to be anti-inflammatory, kinase inhibitors, antiviral, platelet aggregation inhibitors, and immunosuppressive, with probable activity (Pa) greater than probable inactivity (Pi). ZINC5733756 is structurally similar to estradiol with a Tanimoto coefficient value of 0.73, which exhibits anti-inflammatory activity by targeting the activation of Nrf2. Similarly, ZINC1691180 has been reported to elicit anti-inflammatory activity in vitro. The compounds may serve as scaffolds for the design of potential biotherapeutic molecules against the cytokine storm associated with COVID-19.

scholarly journals The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial

2021 ◽  
Vol 30 ◽  
pp. 096368972110249
Author(s):  
G Adas ◽  
Z Cukurova ◽  
K Kart Yasar ◽  
R Yilmaz ◽  
N Isiksacan ◽  
...  
Keyword(s):  
Growth Factors ◽  
Critically Ill ◽  
Inflammatory Cytokines ◽  
Clinical Manifestations ◽  
Systematic Effect ◽  
Cytokine Storm ◽  
Group 3 ◽  
Anti Inflammatory ◽  
Group 2 ◽  
Group 1

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

scholarly journals Effects of esculentoside A on turnour necrosis factor production by mice peritoneal macrophages

1992 ◽  
Vol 1 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Fang Jun ◽  
Zheng Qin Yue ◽  
Wang Hong Bin ◽  
Ju Dian Wen ◽  
Yi Yang Hua
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Inflammatory Mediator ◽  
Platelet Activating Factor ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Necrosis Factor ◽  
Inflammatory Effect

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments showed that it had strong anti-inflammatory effects. Tumour necrosis factor (TNF) is an important inflammatory mediator. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNF production from macrophages was altered by EsA under lipopolysaccharide (LPS) stimulated conditions. EsA was found to decrease both extracellular and cell associated TNF production in a dose dependent manner at concentrations higher than 1 μmol/l EsA. Previous studies have showed that EsA reduced the releasing of platelet activating factor (PAF) from rat macrophages. The reducing effects of EsA on the release of TNF and PAF may explain its anti-inflammatory effect.

scholarly journals Antipyretic, Analgesic and Anti-inflammatory Activity of Qurs Afsanteen Saghir (A Polyherbal Unani Tablet) in Experimental Animals

2022 ◽  
Author(s):  
MD Maseehullah ◽  
Gulam Mohammed Husain ◽  
Mohammed Zakir ◽  
Mohd Kashif Husain ◽  
Ghazala Javed ◽  
...  
Keyword(s):  
Diclofenac Sodium ◽  
Study Drug ◽  
Prunus Dulcis ◽  
Inflammatory Activity ◽  
Apium Graveolens ◽  
Dependent Manner ◽  
Test Drug ◽  
Artemisia Absinthium ◽  
Hot Plate Test ◽  
Anti Inflammatory

Qurs Afsanteen Saghir is a polyherbal Unani formulation in the form of tablet. This formulation consists of multiple medicinal plants like Afsanteen (Artemisia absinthium L.), Badam Talkh (Prunus dulcis (Mill.) D.A.Webb), Asaroon (Asarum europaeum L.), Anisoon (Pimpinella anisum L.) and Tukhm-e-Karafs (Apium graveolens L.). The clinical adult dose of study drug is 3.5 –7 g per day as mentioned in Unani literature. The present study evaluated the antipyretic, analgesic and anti-inflammatory potential of Qurs Afsanteen Saghir using different animal models. Antipyretic activity was measured using yeast-induced pyrexia model in rats at 360 and 720 mg/kg bw dose of test drug and paracetamol (70 mg/kg bw p.o.) as standard control. Analgesic effect was evaluated using acetic acid-induced writhing test in mice using test drug at dose 720 and 1440 mg/kg bw and diclofenac sodium (15 mg/kg bw p.o.) as standard control. Eddy’s hot plate test was conducted in rats using test drug at the dose of 360 and 720 mg/kg bw and buprenorphine (0.10 mg/kg s.q.) as standard control. Anti-inflammatory activity was assessed by carrageenan-induced paw edema model in rats with the dose of 360 and 720 mg/kg of test drug and Indomethacin (10 mg/kg p.o.) as standard control. The study drug significantly reduced the temperature and pain at both dose levels in a time-dependent manner as compared to normal control. However, the reduction of inflammation was observed at low dose (360 mg/kg bw) only after 3 hours of carrageenan administration. These findings indicated that tested drug showed potential activity as antipyretic and analgesic; whereas the drug may not be considered quite effective as an anti-inflammatory agents.

scholarly journals Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model

2021 ◽  
Vol Volume 16 ◽  
pp. 7137-7151
Author(s):  
Fiorenza Rancan ◽  
Xiao Guo ◽  
Keerthana Rajes ◽  
Polytimi Sidiropoulou ◽  
Fatemeh Zabihi ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Topical Delivery ◽  
Inflammatory Activity ◽  
Culture Model ◽  
Anti Inflammatory

scholarly journals Study to Investigate the anti-inflammatory effect of Codelac® Broncho with Thymus Serpyllum (elixir) in comparison with reference drug Fenspiride (syrup) using accute Carrageenan-induced Paw Inflammation Model

2019 ◽  
Vol 5 (1) ◽  
pp. 45-52
Author(s):  
Pavel D. Kolesnichenko ◽  
Anna A. Peresypkina ◽  
Artem A. Poromov ◽  
Elena N. Kareva ◽  
Alexey N. Demidenko
Keyword(s):  
Inflammatory Activity ◽  
C Reactive Protein ◽  
Reference Drug ◽  
Reactive Protein ◽  
Model Control ◽  
Anti Inflammatory ◽  
Thymus Serpyllum ◽  
Carrageenan Inflammation ◽  
Subplantar Injection ◽  
Inflammatory Effect

Introduction: Evaluation of anti-inflammatory action of Codelac® Broncho with Thymus Serpyllum (elixir) in comparison with Fenspiride was carried out on the model of acute carrageenan inflammation of the paws in rats. Materials and methods: Edema was caused by subplantar injection of 0.1 ml of 1% λ- carrageenan gel into the hind paw. The severity of edema was assessed by using 37140 plethysmometer (UGO BASILE, Italy). The measurements were performed before edema induction and 1, 2, 4, 12, 24, 48, 72, 96 and 120 hours afterwards. Anti-inflammatory activity of the drugs was also evaluated based on the analysis of rats’ blood, C-reactive protein concentration and histological examination results. Results and discussion: A decrease in the paw volume increment was revealed in the group with the studied drug in comparison with the group with the carrageenan edema model (control) 4, 12, 24 hours after injection of carrageenan (p<0.05). As a result of plethysmometry, a more pronounced anti-inflammatory effect of the studied drug than that of Fenspiride was revealed. There was a significant decrease in the levels of leukocytes (p<0.05), lymphocytes (p<0.05), monocytes (p<0.05) and neutrophils (p<0.05) in the group with the studied drug compared to those the the control 48 hours after the initiation of edema, while in the group with Fenspiride, there was only a decrease in the levels of leukocytes (p<0.05) and lymphocytes (p<0.05). There were no differences in the concentration of C-reactive protein between the groups. Conclusion: The obtained data indicate a more pronounced anti-inflammatory activity of Codelac® Broncho with Thymus Serpyllum in comparison with Fenspiride, on the model of acute carrageenan inflammation of the paw in rats.

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