In Vitro and In Vivo Experimental Model-based Approaches for Investigating Anti-inflammatory Properties of Coumarins.

BACKGROUND: Coumarins are polyphenolic compounds that are often used to treat inflammatory conditions in complementary and alternative medicine. OBJECTIVE: In this study, we reviewed reports of in vivo and in vitro experimental modelbased approaches investigating the potential anti-inflammatory properties of coumarins. METHODS: A literature search of PUBMED, MEDLINE, Web of Science, and Scopus was performed covering the period from 1 January 2005 to 31 December 2015. The keywords used to search were 'anti-inflammatory' and 'coumarin' and 'in vivo' or 'in vitro'. This search identified 425 article titles. RESULTS: Of the 425 article titles, 127 full-text articles were reviewed, and 69 of them were included in the analysis. Most of the studies (81.2%) used in vitro assays. The studies focused on cytokines such as tumour necrosis factor (TNF), interleukin (IL)-6, and IL-1-ß (55.1%), as well as oedema (46.5%), nitric oxide (NO, 23.2%), oxidative stress (21.7%), inflammatory cells (21.7%), nuclear factor (NF)-κB (24.6%), mitogen-activated protein kinase (MAPK, 13%), myeloperoxidase (MPO, (15.9%), cyclooxygenase (COX)-2 (14.5%), prostaglandin E2 (PGE2, 8.7%), 5-lipoxygenase (LOX, 4.3%), and adhesion molecules (7.2%). Coumarins inhibited all these parameters except for IL-10, nuclear factor erythroid 2 (NFE2)-related-factor 2 (Nrf2), and regulatory T cell (Treg) differentiation. CONCLUSION: In vitro methods were the most commonly used to study the antiinflammatory effects of coumarins. The results showed that coumarins exerted antiinflammatory and antioxidant activities by inhibiting NF-κB, nuclear factor of activated T cells (NFAT), retinoic acid-related orphan receptor γτ (RORγτ), and MAPK and increasing Nrf2 activation. These results suggest that coumarins could be important candidates for the development of novel anti-inflammatory therapeutic drugs.

Diagnóstico de febre amarela em tecidos fixados em formalina e emblocados em parafina de primatas não humanos: a importância do exame histopatológico

Os casos de óbitos ou convalescência de primatas não-humanos (PNH) por febreamarela (epizootias) apontam a circulação do vírus em uma determinada região e podemanteceder a ocorrência dessa doença em humanos. Portanto, o diagnóstico adequado destaenfermidade nos diferentes gêneros de PNH presentes no Brasil é importante para adoçãode medidas estratégicas de controle da FA, como a vacinação. O Centro de Patologiado Instituto Adolfo Lutz (CPA-IAL), laboratório de referência macrorregional, participado Programa de Vigilância de Epizootias em PNH do Ministério da Saúde, por meioda realização de exames histopatológico e imuno-histoquímico para FA. Este trabalhoapresenta a casuística recebida e analisada no CPA-IAL durante o ano de 2017. Foramavaliadas amostras de 2.171 PNH, com resultado de 626 positivas no exame imunohistoquímico do fígado (28,83%). Destas, o estado de preservação foi satisfatório em580 e insatisfatório devido à autólise em 132. Das satisfatórias...

Epizootics of Yellow Fever in non-human primates (NHP) are indicative of viralcirculation of the Yellow Fever virus (YFV) and may predict the occurrence of humancases. Therefore, adequate diagnosis of the disease in the different genera of NHPoccurring in Brazil is important for YF control strategies, such as vaccination. ThePathology Center of the Adolfo Lutz Institute (CPA-IAL), a macro-regional referencelaboratory, participates in the Epizootic Surveillance Program through histopathologicaland immunohistochemical exams for YF. This study presents the caseload received andanalyzed at the CPA-IAL during 2017, with especial emphasis on YF immunopositivityin the liver. Samples from 2,171 NHPs were evaluated in 2017. From these, 626 (28.83%)were positive by immunohistochemistry; 580...

From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis.

INTRODUCTION: Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis. METHODS: This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group. RESULTS: Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF. CONCLUSIONS: The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.

Calea uniflora Less. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

Calea uniflora Less. (family Asteraceae), also named "arnica" and "erva-de-lagarto", is a native plant to the South and Southeast of Brazil. This species was used to treat rheumatism, respiratory diseases, and digestive problems in Brazilian folk medicine. In vitro studies have shown the important biological effects of C. uniflora. However no studies have focused on the mechanism of action of anti-inflammatory activity of C. uniflora. The aim of this study was to evaluate the anti-inflammatory effects of the crude extract, its fractions, and isolated compounds obtained from of C. uniflora, using mouse model of carrageenan-induced inflammation. The following inflammatory parameters: leukocyte influx, degree of exudation, myeloperoxidase (MPO) and adenosine deaminase (ADA) activities, nitric oxide metabolites (NOx), proinflammatory cytokines and phosphorylation of the p65 subunit of NF-κB (p-p65 NF-κB), and p38 mitogen-activated protein kinase (p-p38 MAPK) levels were determined. The crude extract of C. uniflora, its fractions and its isolated compounds reduced the leukocyte influx, degree of exudation, MPO and ADA activities, NOx, TNF-α, IFN-γ, MCP-1 and IL-6 levels (p<0.05). The isolated compounds reduced p-p65 NF-κB and p-p38 MAPK levels (p<0.01). This study demonstrated that C. uniflora exhibits a significant anti-inflammatory activity via inhibition of the leukocyte influx and degree of exudation. These effects were associated with a decrease in the levels of several proinflammatory mediators. The mechanism of the anti-inflammatory action of C. uniflora may be, at least in part, via the inhibition of p65 NF-κB and p38 MAPK activation by the isolated compounds.

Beneficial effect of Ageratum conyzoides Linn (Asteraceae) upon inflammatory response induced by carrageenan into the mice pleural cavity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides Linn (Asteraceae), a tropical plant that is very common in West Africa and some parts of Asia and South America, has been used to treat inflammatory disorders. In Brazil, teas made from A. conyzoides L. are used as anti-inflammatory, analgesic and anti-diarrheic agents. Therefore, it is necessary to study the mechanism of anti-inflammatory action of A. conyzoides L. to support its medicinal use for treating inflammatory conditions. These studies will also support the development of effective pharmacological agents with potent anti-inflammatory properties. AIM OF THE STUDY: To evaluate the anti-inflammatory effects of the crude extract (CE), its derived fractions: ethanol (EtOH-F), hexane (HEX-F), ethyl acetate (EtOAc-F) and dichloromethane (DCM-F) and isolated compounds, such as 5'-methoxy nobiletin (MeONOB), 1,2-benzopyrone and eupalestin, which are obtained from the aerial parts of A. conyzoides L. MATERIALS AND METHODS: These evaluations were performed using an animal model of inflammation induced by carrageenan. The following inflammatory parameters were analysed: leukocyte influx, protein concentration of the exudate, myeloperoxidase (MPO), adenosine deaminase (ADA) and nitric oxide metabolites (NOx) concentrations, interleukin 10 (IL-10), interleukin 17A (IL-17A), interleukin 6 (IL-6), tumor necrosis factor (TNF), interferon gamma (IFN-γ) and phosphorylation of p65 subunit of NF-κB (p-p65 NF-κB), p38 mitogen-activated protein kinases (p-p38 MAPK) were also analysed. RESULTS: CE, its EtOH-F, HEX-F, EtOAc-F and DCM-F and the isolated compounds, including MeONOB, 1,2-benzopyrone and eupalestin, significantly reduced leukocyte influx, protein concentration of the exudate, MPO, ADA, and NOx concentrations (p<0.05). CE, EtOH-F and isolated compounds significantly reduced IL-17A, IL-6, TNF and IFN-γ levels (p<0.05). CE, EtOH-F and isolated compound 1,2-benzopyrone also increased IL-10 levels (p<0.05). Isolated compounds, MeONOB, 1,2-benzopyrone and eupalestin, reduced p-p65 NF-κB and p-p38 MAPK (p<0.01). CONCLUSIONS: This study demonstrates that A. conyzoides L. exerts its important anti-inflammatory properties by inhibiting leukocyte influx and protein concentration of the exudate, as well as reducing the levels of several pro-inflammatory mediators. The anti-inflammatory action of A. conyzoides L. may be because of the inhibition of p65 NF-κB and MAPK activation by the isolated compounds.