scholarly journals Synthesis of some Heterocyclic compounds bearing Coumarin nucleus and their Anti-inflammatory activity

2016 ◽  
Vol 12 (5) ◽  
pp. 4442-4452 ◽  
Author(s):  
Nadia T. A. Dawoud1 ◽  
Nahed. F.Abdel-Ghaffar ◽  
Mona M Abdl-gali ◽  
Fekria M. A. Soliman ◽  
Heba M Zaki

Starting from 6-amino-4-methyl-2H-chromen-2-one 1, a series of some new heterocyclic compounds (2-14) incorporating coumarin moiety was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. The tested coumarin derivatives reduce the edema volume and serum levels of the pro inflammatory cytokines, IL-6 and TNF-α, and have effects on promoting production of anti-inflammatory cytokine, IL-10.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation


2019 ◽  
Vol 27 (2) ◽  
pp. 189-198
Author(s):  
Raluca Elena Tripon ◽  
Ioana Berindan Neagoe ◽  
Livia Budisan ◽  
Tudor Lucian Pop ◽  
Victor Cristea ◽  
...  

Abstract Introduction: Community-acquired pneumonia (CAP) is still one of the major causes of morbidity and mortality worldwide. Pro-inflammatory and anti-inflammatory interleukins have been studied to elucidate the role that inflammation plays in its pathogenesis. The aim of this study is to investigate inflammation in CAP, by analyzing in dynamic, serum levels of six interleukins (IL) and their predictive value regarding adverse outcomes. Materials and methods: Forty adult patients with CAP, admitted in the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania from December 2015 to February 2017, were enrolled in this study. Serum levels of pro-inflammatory: IL1β, TNF-α, IL-6, anti-inflammatory: IL-10 and IL-4, along with IL-17A were analyzed in dynamic, on day 1 and day 4.The receiver – operator curves (ROC) were used to analyze the outcome prediction of IL. Results: Serum levels of IL-1β, IL-6, TNF-α and IL-10 have decreased significantly in dynamic, while IL-4 increases. IL-17A has acted like a pro-inflammatory cytokine. We have found a correlation between IL-6 and IL-10 (r=0.429, p=0.000), IL-6 and IL-17A (r=0.295, p=0.008) and IL-10 and IL-17A (r=0.475, p=0.000). Out of 40 patients, 9 had adverse outcomes, consisting in 9 relapses from which 1 died. IL-6 discriminates alone between adverse and favorable outcomes. With multivariate analysis and multiple regression of all combined IL, we have found that there is a predictive model regarding adverse outcomes. Conclusion: IL-10 and IL-17A behave like pro-inflammatory cytokines. IL-6 is a predictive marker for adverse outcomes alone. All IL studied together have an impact on adverse outcomes.


2021 ◽  
Vol 23 (4) ◽  
pp. 536-540
Author(s):  
O. M. Bilyi ◽  
N. A. Mitriaieva ◽  
M. V. Krasnoselskyi ◽  
L. V. Hrebinyk

Secondary edematous breast cancer (SEBC), T4b, has a poor prognosis. The aim of this study is to examine the balance in serum levels of pro-inflammatory (TNFά, IL-8) and anti-inflammatory (IL-4) cytokines in patients with SEBC before special treatment. Materials and methods. A total of 87 patients with breast cancer (BC) were examined before treatment: 42 patients with SEBC in T4bN0-3M0 stage and 45 BC patients in T3-4N1-3M0 stage without edema. The control group consisted of 15 patients with fibroadenomas. The serum levels of cytokines (IL-4, IL-8, TNFά) in the patients was determined using the enzyme-linked immunosorbent assay. Results. In the SEBC patients as compared to the patients without cancer, the serum pro-inflammatory cytokine (IL-8, TNFά) levels were significantly increased and the anti-inflammatory cytokine (IL-4) level was slightly increased in 22 %. In BC without edema, an imbalance was noted in favor of pro-inflammatory cytokines, but in SEBC it was more pronounced (31.6 versus 12.4 and 5.6 versus 3.2, respectively). Conclusions. In the majority of SEBC patients, there is an imbalance in the cytokine profile in favor of the pro-inflammatory cytokines (IL-8, TNFά). SEBC patients with elevated levels of both pro- and anti-inflammatory cytokines before treatment are the highest risk group of tumor progression and metastasis. Inhibition of the IL-8 effects or related CXC chemokines, TNFά, and others may have important consequences for the systemic treatment of SEBC.


2018 ◽  
Vol 51 (5) ◽  
pp. 2290-2308 ◽  
Author(s):  
Xiaochuan Chen ◽  
Bo Yang ◽  
Jun Tian ◽  
Hong Hong ◽  
Yu Du ◽  
...  

Background/Aims: Increasing evidence has demonstrated the novel roles of mesenchymal stem cells (MSCs) in immunotherapy. However, difficulty in acquiring these cells and possible ethical issues limited their application. Recently, we have isolated a unique MSC population from dental follicles with potent stem cell-like properties. This study focused on the effects of dental follicle stem cells (DFSCs) on macrophage activation and polarization to determine their role in immunomodulation and to test if DFSCs are a promising cell source for MSC-based immunotherapy. Methods: Rat acute lung injury (ALI) models induced by Lipopolysaccharide (LPS) were applied to test the immune-modulatory effects of DFSC/DFSC-CM in vivo. The pulmonary permeability was determined by the dry / wet weight ratios of the left upper lung lobe. The lung histopathological damage was graded on a 0 to 4+ scale. And the inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were tested by ELISA. Then we established LPS-induced inflamed macrophage models in vitro. Inflammatory cytokine production and polarization marker expression were measured by RT-qPCR, ELISA, western blot and flow cytometric analysis in macrophages following DFSC-CM treatment. The paracrine factors in DFSC-CM were revealed by a RayBiotech Protein Array. Thereafter, neutralization studies were performed to confirm the potential immune regulators in DFSC-CM. Results: The DFSC/DFSC-CM not only attenuated histopathological damage and pulmonary permeability, but also downregulated pro-inflammatory cytokines MCP-1, IL-1, IL-6 and TNF-α, and upregulated anti-inflammatory cytokine IL-10 in BALF. Immunofluorescence staining revealed the increased expression of macrophage M2 marker Arg-1. Further in vitro study revealed that macrophages switched to an anti-inflammatory M2 phenotype when co-cultured with DFSC-CM, characterized by suppressed production of pro-inflammatory cytokines MCP-1, IL-1, IL-6, TNF-α and M1-polarizing markers iNOS and CD86; and increased expression of the anti-inflammatory cytokine IL-10 and the M2-polarizing markers Arg-1 and CD163. A RayBiotech Protein Array revealed 42 differentially expressed (> 2-fold) paracrine factors in DFSC-CM compared with the serum-free Ham’s F-12K medium, among which TGF-β3 and Thrombospondin-1 (TSP-1) were upregulated by 18- and 105-fold, respectively. Neutralization studies confirmed the immunoregulatory roles of TGF-β3 and TSP-1 in macrophage activation and polarization. Conclusion: These results indicated that DFSCs can reprogram macrophages into the anti-inflammatory M2 phenotype, the paracrine factors TGF-β3 and TSP-1 may be one of the underlying mechanisms. This study supports the hypothesis that DFSCs are promising for MSC-based immunotherapy.


2017 ◽  
Vol 16 (10) ◽  
pp. 2403-2410
Author(s):  
Haoran Ma ◽  
Fuqian Wang ◽  
Jie Jiang ◽  
Lu Cheng ◽  
Hong Zhang ◽  
...  

Purpose: To evaluate the anti-inflammatory activity of Liquidambar formosana  Hance infructescence (Liquidambaris fructus, ELF) in vivo, and clarify its underlying mechanisms. Methods: The in vivo anti-inflammatory activity of ELF was examined by xylene-induced ear swelling test in mice as well as carrageenan-induced paw edema method in rats. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in serum were measured by enzyme-linked immunosorbent assay (ELISA), while the expressions of COX-2, iNOS and NF-κB p65 in paw tissue of rats were evaluated by western blot.Results: After ELF treatment, the levels of TNF-α (p < 0.001), IL-1β (p < 0.001) and IL-6 (p < 0.001) in serum decreased and the levels of anti-inflammatory cytokine IL-10 increased (p < 0.01). In addition, ELF treatment resulted in decrease of COX-2 (p < 0.01), iNOS (p < 0.01) and NF-κB p65 (p < 0.01) expressions in Wistar rats.Conclusion: The results reveal that ELF possesses significant anti-inflammatory effect in vivo. The anti-inflammatory activity is associated with the levels of TNF-α, IL-1β, IL-6 and IL-10 in serum. Furthermore, the suppression of NF-κB p65, iNOS and COX-2 is linked to its anti-inflammatory effect. These results provide a rationale for the use of Liquidambaris fructus in inflammatory disease in traditional medicine.Keywords: Anti-inflammatory activity, Liquidambaris fructus, Cytokines, Ear swelling test, Paw edema


2008 ◽  
Vol 116 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Christian Stumpf ◽  
Sebastian Petzi ◽  
Katrin Seybold ◽  
Gerald Wasmeier ◽  
Martin Arnold ◽  
...  

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg·kg−1 of body weight·day−1 via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-α, IL-6 and IL-10 protein, the TNF-α/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dtmax, +147%; and LV end-diastolic pressure, −27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-α, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-α/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.


Author(s):  
Adryan Fristiohady ◽  
Muhammad Hajrul Malaka ◽  
Andi Rizqa Wahyuni Safitri ◽  
Dewo Diha ◽  
Saripuddin Saripuddin ◽  
...  

Inflammation is the host's protective response to any stimulus that harms the body. Excessive inflammatory process causes tissue damage. Therefore, an anti-inflammatory agent is needed. The use of natural ingredients, especially sea sponges, is an option to reduce the side effects of anti-inflammatory agents. This utilization is related to the discovery of new agents. So, we tested the effect of the ethanol extract of Petrosia sp. as an anti-inflammatory agent. Animal induced with 1% carrageenan and left for 1 hour. After that the animals were divided into 6 groups (n = 4) and given oral treatment, namely: Group I (normal group); Group II (negative group); Group III (ethanol extract of Petrosia sp. Concentration of 0.05mg/ml); Group IV (ethanol extract of Petrosia sp. Concentration 0.1mg/ml); Group V (ethanol extract of Petrosia sp. Concentration 0.2mg/ml); and Group VI (positive group, Diclofenac Sodium). After 1 hour, the animals were measured for edema volume and plasma TNF-α levels. Based on the research conducted, the ethanol extract of Petrosia sp. decreased edema volume and plasma TNF-α levels in inflammatory mice. The concentration of 0.2mg/mL had a significant effect on the negative control used (p <0.05). On the other hand, Petrosia sp. indicates the presence of alkaloids, flavonoids, and steroids. They may play an important role in the anti-inflammatory process. Thus, it can be concluded that the ethanol extract of Petrosia sp. has anti-inflammatory activity.


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