Due to their large spectrum of bioactive properties, much attention has recently been drawn to phlorotannins—i.e., phenolic compounds characteristic from brown macroalgae. This study aimed to evaluate the antioxidant and anti-inflammatory properties of F. vesiculosus phlorotannin extracts and purified fractions. Overall, the crude extract and its ethyl acetate fraction (EtOAc) showed good radical scavenging activity, particularly towards nitric oxide (NO^•). Subsequent subfractions of EtOAc (F1 to F9) with different molecular weights were then shown to inhibit lipopolysaccharide-induced NO^• production in macrophages, with stronger effects being observed for fractions of lower MWs. Of the three intracellular markers analyzed, inducible NO^• synthase showed the highest sensitivity to almost all the phlorotannin-rich samples, followed by interleukin 1β and cyclooxygenase 2, which was only inhibited by F2. Furthermore, this subfraction inhibited the phosphorylation and degradation of inhibitory protein κBα, thus preventing the activation of NF-κB and blocking the inflammatory cascade at the transcriptional level. This sample was characterized by the presence of a major compound with a deprotonated molecular ion at m/z 507 with a fragmentation pattern coherent with that of a phlorotannin derivative. Overall, this work unveiled some of the mechanistic aspects behind the anti-inflammatory capacity of phlorotannins from F. vesiculosus, endorsing its use as a possible natural source of anti-inflammatory compounds.

Inflammation is a defensive response of the organism to manage harmful stimuli sensed by innate immune cells. The signal alarm is triggered by the recognition of pathogen-associated molecular patterns, such as microbial components, or host-derived damage-associated molecular patterns (DAMPs), namely high-mobility group box 1 protein (HMGB1) and purine metabolites, through a set of highly conserved receptors in immune cells termed pattern recognition receptors. Among these receptors, membrane-associated toll-like receptors (TLRs) and cytosolic nucleotide binding and oligomerization domain (nod)-like receptors (NLRs) assume particular relevance in the inflammatory process. Once activated, NLRs induce the assembly of multiprotein complexes called inflammasomes, leading to production of proinflammatory cytokines (e.g., interleukin-1) and induction of inflammatory cell death (pyroptosis) through the activation of caspase-1. Although these processes intend to protect the body from insults, prolonged or exacerbated inflammatory responses associated with inflammasome activation are related to a growing number of diseases. Recently, inflammasome activation and autophagy were shown to be linked and to mutually influence each other. Therefore, we aim, in this review, to discuss the recent evidences concerning the cross talk between autophagy and inflammasome activation and its potential roles in disease progression.

Myocardial ischaemia is associated with an exacerbated inflammatory response, as well as with a deregulation of intercellular communication systems. Macrophages have been implicated in the maintenance of heart homeostasis and in the progression and resolution of the ischaemic injury. Nevertheless, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages remain largely underexplored. Extracellular vesicles (EVs) have emerged as key players of cell‐cell communication in cardiac health and disease. Hence, the main objective of this study was to characterize the impact of cardiomyocyte‐derived EVs upon macrophage activation. Results obtained demonstrate that EVs released by H9c2 cells induced a pro‐inflammatory profile in macrophages, via p38MAPK activation and increased expression of iNOS, IL‐1β and IL‐6, being these effects less pronounced with ischaemic EVs. EVs derived from neonatal cardiomyocytes, maintained either in control or ischaemia, induced a similar pattern of p38MAPK activation, expression of iNOS, IL‐1β, IL‐6, IL‐10 and TNFα. Importantly, adhesion of macrophages to fibronectin was enhanced by EVs released by cardiomyocytes under ischaemia, whereas phagocytic capacity and adhesion to cardiomyocytes were higher in macrophages incubated with control EVs. Additionally, serum‐circulating EVs isolated from human controls or acute myocardial infarction patients induce macrophage activation.According to our model, in basal conditions, cardiomyocyte‐derived EVs maintain a macrophage profile that ensure heart homeostasis, whereas during ischaemia, this crosstalk is affected, likely impacting healing and post‐infarction remodelling.