The aim of the present study was to investigate a cytotoxic oxidative cell stress related and the antioxidant profile of kaempferol, quercetin, and isoquercitrin. The flavonol compounds were able to act as scavengers of superoxide anion (but not hydrogen peroxide), hypochlorous acid, chloramine and nitric oxide. Although flavonoids are widely described as antioxidants and this activity is generally related to beneficial effects on human health, here we show important cytotoxic actions of three well known flavonoids. They were able to promote hemolysis which one was exacerbated on the presence of hypochlorous acid but not by AAPH radical. Therefore, despite they expected scavenger action over free radicals an oxidants, these compounds could be very lesive to living organisms by acting over erythrocytes and maybe other cellular types.

Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3 , ASC and caspase-1 . All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1β, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.

Based on the fact that Synadenium grantii is used in folk medicine for the treatment of peptic ulcers and inflammatory diseases, this work describes its chemical and pharmacological properties. Pharmacological investigation of the crude bark extract showed a high antioxidant activity over several scavenger systems, such as 2,2'-azino-bis (3-ethylenebenzothiazoline-6-sulfonic acid)• +, 1-diphenyl-2-picrylhydrazyl•, O2 • - , and HOCl, as well as an enzymatic system with human myeloperoxidase and an ex vivo hemolysis system. Furthermore, the oral administration of the crude bark extract was able to reduce carrageenan-induced rat paw edema as effectively as ibuprofen. These biological activities may be associated with the presence of flavonoids and terpenes, as revealed by HPLC and NMR analyses of the crude stem bark extract. The phytochemical investigations in this study resulted in the isolation of friedelin and 3β-friedelinol for the first time, while euphol and lanosterol were also isolated.

The available information about the role of Dectin-1 in sporotrichosis is scarce. Hence, we aimed to assess Dectin-1 expression by macrophages and the activation of some related antifungal mechanisms during the Sporothrix schenckii sensu stricto infection as a first attempt to elucidate the role of this receptor in sporotrichosis. Balb/c mice were intraperitoneally infected with S. schenckii sensu stricto yeast ATCC 16345 and euthanized on days 5, 10 and 15 post-infection, when the following parameters were evaluated: fungal burden in spleen, Dectin-1 expression and nitric oxide (NO) production by peritoneal macrophages, as well as IL-1β, TNF-α and IL-10 ex vivo secretion by these same cells. Peritoneal macrophages were ex vivo challenged with either the alkali-insoluble fraction (F1) extracted from the S. schenckii cell wall, a commercially available purified β-1,3-glucan or whole heat-killed S. schenckii yeasts (HKss). Additionally, a Dectin-1 antibody-mediated blockade assay was performed on day 10 post-infection to assess the participation of this receptor in cytokine secretion. Our results showed that Dectin-1 expression by peritoneal macrophages was augmented on days 10 and 15 post-infection alongside elevated NO production and ex vivo secretion of IL-10, TNF-α and IL-1β. The antibody-mediated blockade of Dectin-1 inhibited cytokine production in both infected and non-infected mice, mainly after β-1,3-glucan stimulation. Our results suggest a role for Dectin-1 in triggering the immune response during S. schenckii infection.