Ketoconazole-p Aminobenzoic Cocrystal Exhibits a Potent Anti-inflammatory Effect on the Skin of BALBc Mice 

Author(s):  
Sorina Danescu ◽  
Gabriela Adriana Filip ◽  
Remus Moldovan ◽  
Diana Olteanu ◽  
Andras Nagy ◽  
...  

Abstract Fungal infections are a growing global health problem. Therefore, our group has designed and characterized a novel cocrystal formulation starting from ketoconazole and para-amino benzoic acid, named KET-PABA aiming to improve the bioavailability, biocompatibility, and efficiency of the parent drug. The cocrystal showed improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency as compared to ketoconazole. The current study investigated the local possible side effects induced on BALBc mice skin by the application of KET-PABA cocrystal. KET-PABA proved to be safe, without signs of skin sensitization as shown by the mouse ear sensitization test (MEST), or histopathology. KET-PABA induced a potent anti-inflammatory effect through the inhibition of proinflammatory cytokines such as IL1α, IL1β, IL6 and TNFα, and other inflammation promoters such as NRF2, compared to the vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NFκB pathway. Overall, KET-PABA application induced no sensitization, moreover, it induced an anti-inflammatory response. Based on the improved antimycotic effect versus ketoconazole and the anti-inflammatory action, KET-PABA cocrystal has the potential to be an efficient drug in the treatment of cutaneous mycosis.

2018 ◽  
Vol 773 ◽  
pp. 360-364 ◽  
Author(s):  
Sroisiri Thaweboon ◽  
Boonyanit Thaweboon ◽  
Rattiporn Kaypetch

This study aimed to investigate the antifungal, anti-inflammatory and cytotoxic effects of Zingiber cassumunar gel. The gel was prepared from essential oil of Zingiber cassumunar rhizome by the Thailand Institute of Scientific and Technological Research. Antifungal activity of the gel was firstly determined by the well diffusion method against Candida albicans ATCC 10238 and candida strain isolated from the patient’s lesion. Then, the Agar overlay technique was used to test the cytotoxicity of Z. cassumunar gel on mouse fibroblasts (ATCC clone 929) according to ISO 7405. For anti-inflammatory effect of the gel, TPA (carrageenan lambda type IV, 12-O-tetradecanoylphorbol-13- acetate)-induced mouse ear edema method was used. The results of well diffusion showed that Z. cassumunar gel was quite a potent antifungal agent against both strains of tested C. albicans with inhibition zones of 12-13 mm. In the cytotoxicity test, the gel exhibited no toxicity to cell culture. In addition, topical administration of Z. cassumunar gel could decrease mouse ear edema induced by TPA. At 30 and 60 min-time points, Z. cassumunar gel showed higher anti-inflammatory activity than triamcinolone which was used as reference anti-inflammatory drug. In conclusion, gel prepared from Z. cassumunar oil showed antifungal activity against both strains of C. albicans. In addition, its anti-inflammatory effect was demonstrated within 30 min by the TPA-induced mouse ear edema model. The gel was non-toxic to cell culture after 24-h incubation. Further studies are needed to clarify the safety and benefit of this gel for clinical use in the treatment of candidal infection and inflammation.


Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 495-499 ◽  
Author(s):  
George Asimakopoulos ◽  
Kenneth M Taylor ◽  
Dorian O Haskard ◽  
R Clive Landis

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion ( p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.


2017 ◽  
Vol 45 (2) ◽  
pp. 110-117 ◽  
Author(s):  
Min-Ji Kim ◽  
Min-Ju Kim ◽  
Koth Bong Woo Ri Kim ◽  
Sun Hee Park ◽  
Hyeun Deok Choi ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4058 ◽  
Author(s):  
Hyung Jin Lim ◽  
Seon Gyeong Bak ◽  
Eun Jae Park ◽  
Sae-Kwang Ku ◽  
Soyoung Lee ◽  
...  

Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.


2017 ◽  
Vol 2017 ◽  
pp. 1-12
Author(s):  
Zhenbiao Zhang ◽  
Yingfang Guo ◽  
Yuzhu Liu ◽  
Chengye Li ◽  
Mengyao Guo ◽  
...  

The aim of the present study was to determine the anti-inflammatory effect of IFN-τon endometritis using a mouse model ofS. aureus-induced endometritis and to elucidate the mechanism of action underlying these effects. In the present study, the effect of IFN-τonS. aureusgrowth was monitored by turbidimeter at 600 nm. IFN-τdid not affectS. aureusgrowth. The histopathological changes indicated that IFN-τhad a protective effect on uterus tissues withS. aureusinfection. The ELISA and qPCR results showed the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 was decreased with IFN-τtreatment. In contrast, the level of the anti-inflammatory cytokine IL-10 was increased. We further studied the signaling pathway associated with these observations, and the qPCR results showed that the expression of TLR2 was repressed by IFN-τ. Furthermore, the western blotting results showed the phosphorylation of IκB, NF-κB p65, and MAPKs (p38, JNK, and ERK) was inhibited by IFN-τtreatment. The results suggested that IFN-τmay be a potential drug for the treatment of uterine infection due toS. aureusor other infectious inflammatory diseases.


2017 ◽  
Vol 15 (3) ◽  
pp. 143-151 ◽  
Author(s):  
Rui Fei ◽  
Huan Zhang ◽  
Sheng Zhong ◽  
Baigong Xue ◽  
Yuanqi Gao ◽  
...  

Serine protease inhibitors (serpins) are a superfamily of proteins involved in many important biological processes, including inflammation. Serpins dysfunction-related diseases are mainly treated by augmentation therapy using serpins purified from human plasma. Pnserpin from hyperthermophilic archaeon Pyrobaculum neutrophilum showed protease inhibition activity and high stability. In this study, we examined the anti-inflammatory activity of Pnserpin using xylene-induced acute inflammatory model of mouse ear swelling and lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages cellular model. The inhibition of mouse ear swelling and the production of pro-inflammatory cytokines in mouse serum or in macrophages cell were used to evaluate the anti-inflammatory effect of Pnserpin. Our results showed that Pnserpin could inhibit the xylene-induced mouse ear swelling and suppress the production of pro-inflammatory cytokines in mouse serum and in LPS-induced RAW264.7 cells. This study indicated that Pnserpin might have anti-inflammatory effect in vivo and in vitro.


2013 ◽  
Vol 41 (03) ◽  
pp. 565-584 ◽  
Author(s):  
Wi-Gyeong Gwon ◽  
Min-Sup Lee ◽  
Jong-Soon Kim ◽  
Jae-Il Kim ◽  
Chi-Won Lim ◽  
...  

Sargassum fulvellum (Turner) C. Agardh has been used to treat various inflammatory diseases, including lump, dropsy, swollen and painful scrotum, and urination problems for several centuries with no side effects. This study aims to investigate the anti-inflammatory effect of the hexane fraction of S. fulvellum (HFS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and phorbol 12-myristate 13-acetate (PMA)-induced mouse-ear edema. The anti-inflammatory activity of HFS in LPS-stimulated RAW 264.7 cells was investigated by assessing the inhibition of nitric oxide (NO) and pro-inflammatory cytokine production during Griess reaction and enzyme-linked immunosorbent assay (ELISA), respectively. The molecular mechanisms that underlie the anti-inflammatory action of HFS were investigated by analyzing the activation of transcription factor and its upstream signaling proteins. Additionally, an in vivo study of the anti-inflammatory effect of HFS was carried out using PMA-induced mouse-ear edema. HFS inhibited LPS-induced NO production in a dose-dependent manner and suppressed the expression of inducible NO synthase (iNOS) in the RAW 264.7 cells. Further, HFS reduced the production of pro-inflammatory cytokines in the LPS-stimulated RAW 264.7 cells. HFS significantly inhibited LPS-induced nuclear factor kappa B (NF-κB) transcriptional activity and NF-κB translocation into the nucleus by preventing degradation of inhibitor κB-α. Moreover, HFS inhibited the activation of Akt and mitogen-activated protein kinases (MAPKs) in the LPS-stimulated RAW 264.7 cells. Furthermore, HFS suppressed PMA-induced mouse-ear edema. The above data indicate that the anti-inflammatory effects of HFS on LPS-stimulated cells are associated with the suppression of NF-κB through the inhibition of MAPKs and Akt phosphorylation.


Author(s):  
Арам Дуллах ◽  
І. О. Власенко ◽  
Г. М. Войтенко ◽  
Л. Л. Давтян

<p><strong>STUDY OF ANTIINFLAMMATORY ACTIVITY OF FORMULTATED CREAM BETAKARBOKLOMET</strong></p><p><strong>Aram Dullah, </strong><strong>I</strong><strong>.</strong><strong>O</strong><strong>.Vlasenko, </strong><strong>G</strong><strong>.</strong><strong>M</strong><strong>. </strong><strong>Voytenko</strong><strong>,</strong> <strong>L.L. Davtyan </strong></p><p><em>Shupik</em><em> </em><em>National</em><em> </em><em>medical</em><em> </em><em>academy</em><em> </em><em>of</em><em> </em><em>postgraduate education </em><strong></strong></p><p><strong>Summary:</strong> The article presents the results of a study of antiexudative activity of complexed antifungal cream, based on clotrimazole, betamethasone dipropionate, metronidazole and urea, for treatment of dermatomycosis.  By in vivo method (model of acute aseptic (dextran) inflammation) it was found that the formulated cream has antiinflammatory activity typical for glucocorticoids, dynamics and the value of which correspond to the activity of referent-medicine.</p><p><strong>Keywords: </strong>dermatomycosis, betamethasone diptopionate, antiexudative activity.</p><pre><strong>Introduction.</strong> Last years are characterized by marked increase in the incidence of fungal diseases, foot fungal infections take one of the highest incidence of skin diseases. They are often characterized by thickening of the stratum corneum layer of the foot’s skin, cracks and inflammation, causing pain and itching. The long term of mycological process leads to profound disorders of the body, complicating other diseases and reduces the quality of life.</pre><pre>When dermatomycosis is accompanied by inflammatory reaction of the skin combined using of antifungal agents and corticosteroids of local action is recommended. </pre><pre>Based on pharmaco- technological, physical, chemical and biological research mild drug (MDL) for complex treatment of dermatomycoses based on clotrimazole, metronidazole, urea and betamethasone dipropionate named Betakarboklomet was developed. </pre><pre>The purpose of the study was to investigate the anti-inflammatory activity of developed MDL .</pre><pre><strong>Methods</strong><strong>.</strong> The study of  MDL’s antiexudative activity conducted on a model of acute aseptic ( dextrane) inflammation by oncometric method was conducted. Exudative inflammation was assessed by measuring the volume of paw dynamics.</pre><p><strong>Results</strong><strong> </strong><strong>and</strong><strong> </strong><strong>discussion</strong>.</p><pre>The maximum increase in the volume of inflamed foot was observed within 1 hour after introduction of dextran, averaging 0.78 ml. In the next 5 hours foot swelling gradually decreased, but the output volume is not returned.</pre><pre>The study found that processed cream has expressed antiexudative activity, which is not significantly different from the reference product. Increase the volume of the paw of animals applied by drug Betakarboklomet was at the peak of edema (1 hour) 0,52 ± 0,02 ml , 3 h paw’s growth of volume of the original volume was 0,36 ± 0,02 ml, 5 hours - 0,20 ± 0,01 ml. The average value of MDL action for 5 hours was about 50.98 %, and for the reference product - 47.47 %.</pre><pre>Ability of developed cream Betakarboklomet to inhibit inflammation in the early stages manifested by betamethasone dipropionate, which, according to the literature, is able to reduce the synthesis of prostaglandins , prostacyclin, and others. Thus, our study of impact of developed cream Betakarboklomet on inflammation, suggests that MDL has a strong anti-inflammatory effect ( inhibits the development of serotonin edema).</pre><pre><strong>Conclusions</strong><strong>.</strong> Based on pharmacological studies of experimental inflammation induced by dextran, developed drug Betakarboklomet shows anti-inflammatory effect at the prototype.</pre>


2016 ◽  
Vol 44 (3) ◽  
pp. 236-245 ◽  
Author(s):  
Bo-Kyeong Kang ◽  
Min-Ji Kim ◽  
Da-Hyun Jeong ◽  
Koth-Bong-Woo-Ri Kim ◽  
Nan-Young Bae ◽  
...  

2020 ◽  
Vol 14 (2) ◽  
pp. 191-199
Author(s):  
Yasuyuki Fujimoto ◽  
Nobuyuki Kuramoto ◽  
Masanori Yoneyama ◽  
Yasu-Taka Azuma

IL-19 is a type of anti-inflammatory cytokine. Since the receptor for IL-19 is common to IL-20 and IL-24, it is important to clarify the role of each of the three cytokines. If three different cytokines bind to the same receptor, these three may have been produced to complement the other two. However, perhaps it is unlikely. Recently, the existence of a novel receptor for IL-19 was suggested. The distinction between the roles of the three cytokines still makes sense. On the other hand, because T cells do not produce IL-19, their role in acquired immunity is limited or indirect. It has been reported that IL-19 causes inflammation in some diseases but does not have an anti-inflammatory effect. In this review, we introduce the current role of IL-19 in each disease. In addition, we will describe the molecular mechanism of IL-19 and its development for the prevention of diseases. IL-19 was previously considered an anti-inflammatory cytokine, but we would like to propose it as an immunoregulatory cytokine.


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