Proinflammatory Pathways: The Modulation by Flavonoids

Abstract

Inflammation is a natural, carefully orchestrated response of the organism to tissue damage, involving various signaling systems and the recruitment of inflammatory cells. These cells are stimulated to release a myriad of mediators that amplify the inflammatory response and recruit additional cells. These mediators present numerous redundancies of functions, allowing a broad and effective inflammatory response, but simultaneously make the understanding of inflammation pathways much difficult. The extent of the inflammatory response is usually self-limited, although it depends on the balance between the pro- and anti-inflammatory signals. When that equilibrium is dislocated, a more widespread inflammatory response may take place. Flavonoids have been shown to be possible alternatives to the traditionally molecules used as anti-inflammatory agents. In fact, the biological activities of flavonoids include the modulation of the diverse phases of inflammatory processes, from the gene transcription and expression to the inhibition of the enzymatic activities and the scavenging of the reactive species. In the present review, the inflammatory network is widely revised and the flavonoids' broad spectrum of action in many of the analyzed inflammatory pathways is revised. This kind of integrated revision is original in the field, providing the reader the simultaneous comprehension of the inflammatory process and the potential beneficial activities of flavonoids.

Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E

“…Reactive oxygen radicals are harmful to biomembranes, but can additionally play a role as mediators in different signaling pathways [1,2]. Depending on their structural features, flavonoids such as prenylated flavones or chalcones, can also be involved in cytotoxic processes [3,4].…”

2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

“…It is also part of a complex physiological protective response to harmful stimuli in a body's attempt to heal itself, through the elimination of the initial cause of cell injury, removing necrotic cells and tissues, and initiating the process of repair. The inflammatory response is induced by chemical mediators produced locally by damaged cells at the site of inflammation or derived from circulating inactive precursors (typically synthesized by the liver) that are activated at the referred site [1]. There are two types of chemical mediators: cell-derived mediators that include histamine and serotonin (preformed mediators in secretory granules) and mediators synthesized as needed such as arachidonic acid (AA) metabolites (leukotrienes, prostaglandins, and platelet-activating factor), cytokines, and nitric oxide; and plasma-derived mediators which include complement activation system, kinin system, and coagulation/fibrinolysis system [2].…”

“…There are two types of chemical mediators: cell-derived mediators that include histamine and serotonin (preformed mediators in secretory granules) and mediators synthesized as needed such as arachidonic acid (AA) metabolites (leukotrienes, prostaglandins, and platelet-activating factor), cytokines, and nitric oxide; and plasma-derived mediators which include complement activation system, kinin system, and coagulation/fibrinolysis system [2]. These mediators are involved in the activation of resident cells such as endothelial and epithelial cells and/or the recruitment and activation of inflammatory cells such as macrophages, monocytes, and neutrophils [1]. Two of these proinflammatory mediators are leukotrienes and prostaglandins that arise via arachidonic acid metabolism.…”

Efeitos anti-inflamatórios de espécies de Pouteria spp. sobre macrófagos murinos RAW 264.7 estimulados com LPS

“…Sua função primária é conter e destruir o patógeno invasor. A migração dos neutrófilos para a área lesionada, bem como sua ativação, ocorre por meio dos seguintes eventos: quimiotaxia (migração do neutrófilo para o local da inflamação através dos mediadores quimiotáticos, que se ligam a receptores dos neutrófilos liberando cálcio e aumentando a motilidade do neutrófilo); marginalização (deslocamento dos neutrófilos para a periferia dos vasos, por ação de fibrinogênios e dos eritrócitos agregados nas vênulas); rolamento na superfície endotelial, pela ação de moléculas de adesão da família das selectinas e adesão através das integrinas; diapedese (transmigração dos neutrófilos através da membrana basal do endotélio das vênulas ao tecido intersticial), e, finalmente, fagocitose (mediada pela opsonização, ingestão e destruição dos patógenos) (Figura 1) RIBEIRO et al, 2015).…”

“…Assim, o desenvolvimento de compostos anti-inflamatórios mais recentes que possuam menos efeitos secundários ainda permanece um desafio para a comunidade científica (KUMAR et al, 2008;RECIO et al, 2012;RIBEIRO et al, 2015). Por isso, a identificação de novas drogas que possam promover a resolução da inflamação e que sejam homeostáticas, modulatórias, eficientes e bem toleradas pelo organismo é de suma importância (DARSHAN E DORESWAMY, 2004).…”