Anthocyanins Function as Anti-Inflammatory Agents in a Drosophila Model for Adipose Tissue Macrophage Infiltration

Abstract

Epidemiological and preclinical studies have demonstrated that bioactive foods like flavonoids, polyphenolic compounds derived from fruits and vegetables, exert a protective action against obesity, cardiovascular disorders, and Adipocyte Tissue Macrophage infiltration (ATM). All these pathologies are characterized by increase in reactive oxygen species (ROS) and in proinflammatory cytokines that have been shown to favor the migration of immune cells, particularly of macrophages, in metabolically active organs like the liver and adipose tissue, that in Drosophila are constituted by a unique organ: the fat body. This study, using a unique Drosophila model that mimics human ATM, reveals the beneficial effects of flavonoids to reduce tissue inflammation. Our data show that anthocyanin-rich food reduces the number of hemocytes, Drosophila macrophages, infiltrating the fat cells, a process that is associated with reduced production of ROS and reduced activation of the JNK/SAPK p46 stress kinase, suggesting a fundamental function for anthocyanins as antioxidants in chronic inflammation and in metabolic diseases.

Protective Effects of Anthocyanins in Obesity‐Associated Inflammation and Changes in Gut Microbiome

“…A study using Drosophila model has shown antioxidant activity of anthocyanins . In this study, anthocyanin‐rich purple corn extract reduced the number of hemocytes (macrophages) in Drosophila after 12 days of supplementation, which is associated with the reduced levels of ROS by anthocyanin, which in turn inhibits the activation of JNK/SAPK p46 stress kinase . Supporting these findings, our recently published results also indicate that tart cherry anthocyanin can increase the antioxidant gene expression levels, such as nuclear factor erythroid 2–related factor 2 (NRF2), in epididymal adipose tissue of tart cherry (4% w/w) fed Zucker fatty rats for 8 weeks compared to control non‐supplemented rats …”

“…[59] In this study, anthocyanin-rich purple corn extract reduced the number of hemocytes (macrophages) in Drosophila after 12 days of supplementation, which is associated with the reduced levels of ROS by anthocyanin, which in turn inhibits the activation of JNK/SAPK p46 stress kinase. [59] Supporting these findings, our recently published results also indicate that tart cherry anthocyanin can increase the antioxidant gene expression levels, such as nuclear factor erythroid 2related factor 2 (NRF2), in epididymal adipose tissue of tart cherry (4% w/w) fed Zucker fatty rats for 8 weeks compared to control non-supplemented rats. [60] To understand the effects of anthocyanin-containing fruits, it is important to compare the effects of whole fruit extracts or powder to purified anthocyanins on obesity and other metabolic alterations.…”

“…Apart from their direct anti‐inflammatory signaling mechanisms, anthocyanins have been credited for attenuation of the production of reactive oxygen species (ROS) . A study using Drosophila model has shown antioxidant activity of anthocyanins . In this study, anthocyanin‐rich purple corn extract reduced the number of hemocytes (macrophages) in Drosophila after 12 days of supplementation, which is associated with the reduced levels of ROS by anthocyanin, which in turn inhibits the activation of JNK/SAPK p46 stress kinase .…”

Drosophila melanogaster: A Model Organism to Study Cancer

“…The role of the inflammatory response to combat infection and tissue injury, through the activation of the immune cells, is conserved also in Drosophila's circulating hemocytes (Lemaitre and Hoffmann, 2007), where most of the signals activated in the fat body results also in ROS production (Dionne, 2014; Vlisidou and Wood, 2015). Indeed, we showed, using a genetic model that harbors an inflammation state in the fat body of larvae that mimic ATM, that reduction of ROS, using exogenous anti-oxidants components like flavonoids and anthiocianins, decreased hemocyte's migration and JNK activation in the cells of fat body (Valenza et al, 2018), suggesting that the converging signaling between the fat body and hemocytes on lipid metabolism and ROS/cytokines in response to stress is conserved also in Drosophila .…”

Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes

“…Our second compound of interest is tart cherry anthocyanins (TCA), also known for their anti-inflammatory and antioxidant effects [21][22][23][24][25][26][27]. Anthocyanins belong to the flavonoid group and mostly found in fruits and vegetables [21,24].…”