Insights into Natural Products in Inflammation

The inflammatory process comprises immune, vascular and cellular biochemical reactions, involving different cells, enzymes, cytokines, eicosanoids and transcription factors. It includes the triggering of signaling cascades, the activation of transcription factors, gene expression, increased levels of inflammatory enzymes, and the release of various oxidants and pro-inflammatory molecules in immune or inflammatory cells. At a damaged site, inflammation is initiated by the migration of immune cells from blood vessels and the release of mediators, followed by the recruitment of inflammatory cells and the release of reactive oxygen species (ROS), reactive nitrogen species (RNS) and pro-inflammatory cytokines, to eliminate foreign pathogens, resolve infection and repair injured tissues. As such, inflammation is beneficial for the host, normally being rapid and self-limiting. Deregulated or chronic inflammatory processes, on the other hand, are in the origin of several pathological conditions, such as asthma, cardiovascular and neurodegenerative diseases, among many others. The search for new alternatives to interfere with key players in inflammation has revealed nature to be a prolific source. The special issue “Natural Anti-Inflammatory Agents” includes twenty-seven works offering interesting insights into the involvement of natural extracts and compounds with different targets of this network. The value of this issue is reflected by the diversity of chemical classes and approaches that are addressed. The main findings and advances achieved in these works are pointed out below. Polyphenols are among the most interesting molecules in nature, and are ascribed several biological activities, including anti-inflammatory properties. Flavonoids, in particular, constitute one of the most represented classes. The neuroprotective effect of licochalcone A, a flavonoid isolated from licorice, was first revealed to be associated with microglia and to have anti-inflammatory effects in Parkinson’s disease models, affecting several targets [1]. It suppressed neuroinflammation by blocking the extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor (NF)-κB p65 pathways in microglia. Licochalcone A suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression and also NO and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-activated BV-2 microglial cells. In addition, it inhibited the production of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6. Tamayose and colleagues evaluated the potential of a flavone derivative (isolated from Peperomia obtusifolia (L.) A. Dietr.) as anti-venom therapy for the treatment of snake bite [2]. 8-C-Rhamnosyl apigenin neutralized the effect of Crotalus durissus terrificus secretory phospholipase A2 (PLA2), by inhibiting the major enzymes involved in arachidonic acid metabolism and by preventing the toxic effects of lipid peroxidation. The anti-inflammatory properties of epigallocatechin 3-gallate (EGCG), a flavan-3-ol, were used to validate a spaceand cost-effective organ culture model that considers the main hallmarks of degenerative intervertebral discs [3]. EGCG inhibited the expression of inflammatory markers (IL-6, and IL-8), collagenases (matrix metalloproteinases (MMP) 1, and MMP3), and pain mediators (iNOS, and prostaglandin-endoperoxide synthase 2 (PTGS2)) in nucleus pulposus (NP) tissue challenged with the diffusion of IL-1β and TNF-α. Besides demonstrating, for the first time, the protective effect of