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Simple Summary: This paper reports the interaction between flavonoids, identified in the chemical matrix of açaí extract, and NLRP3 PYD through computational simulation, as well as the in vitro safety profile and anti-inflammatory effect in macrophages and monocytes of three flavonoids, isolated and combined, via the modulation of the NLRP3 inflammasome. Inflammation is a vital mechanism that defends the organism against infections and restores homeostasis. However, when inflammation becomes uncontrolled, it leads to chronic inflammation. The NLRP3 inflammasome is crucial in chronic inflammatory responses and has become a focal point in research for new anti-inflammatory therapies. Flavonoids like catechin, apigenin, and epicatechin are known for their bioactive properties (antioxidant, anti-inflammatory, etc.), but the mechanisms behind their anti-inflammatory actions remain unclear. This study aimed to explore the ability of various flavonoids (isolated and combined) to modulate the NLRP3 inflammasome using in silico and in vitro models. Computer simulations, such as molecular docking, molecular dynamics, and MM/GBSA calculations examined the interactions between bioactive molecules and NLRP3 PYD. THP1 cells were treated with LPS + nigericin to activate NLRP3, followed by flavonoid treatment at different concentrations. THP1-derived macrophages were also treated following NLRP3 activation protocols. The assays included colorimetric, fluorometric, microscopic, and molecular techniques. The results showed that catechin, apigenin, and epicatechin had high binding affinity to NLRP3 PYD, similar to the known NLRP3 inhibitor MCC950. These flavonoids, particularly at 1 µg/mL, 0.1 µg/mL, and 0.01 µg/mL, respectively, significantly reduced LPS + nigericin effects in both cell types and decreased pro-inflammatory cytokine, caspase-1, and NLRP3 gene expression, suggesting their potential as anti-inflammatory agents through NLRP3 modulation. [ABSTRACT FROM AUTHOR]

The accumulation of oxidized low-density lipoprotein (oxLDL) and its toxicity in the arterial wall have been implicated in atherosclerosis. This study aimed to investigate the mechanisms underlying the atheroprotective effect of bixin, a carotenoid obtained from the seeds of the tropical plant Bixa orellana, on Cu2+-induced LDL oxidation and oxLDL-mediated effects in J774A.1 macrophage cells. Bixin's effects were compared to those of lycopene, a carotenoid widely studied for its cardiovascular protective effects. LDL was isolated from human plasma, incubated with bixin or lycopene (positive control), and subjected to oxidation with CuSO4. Afterward, bixin or lycopene was incubated with J774A.1 macrophage cells and exposed to oxLDL. The levels of ROS, RNS, GSH, nitrite, mitochondrial function, and foam cell formation, as well as the expression of proteins related to the antioxidant and inflammatory status, were evaluated. The effect of bixin in inhibiting in vitro human-isolated LDL oxidation was more potent (5–6-fold) than that of lycopene. Bixin pretreatment reduced the atherogenic signaling triggered by oxLDL in the macrophages, namely the generation of reactive species, disturbance of nitric oxide homeostasis, mitochondrial dysfunction, and foam cell formation. The cytoprotective effects of bixin were accompanied by the upregulation of Nrf2 and the downregulation of the NF-kB pathways. Lycopene showed the same protective effect as bixin, except that it did not prevent mitochondrial dysfunction. The efficient performance of bixin makes it an ideal candidate for further trials as a new nutraceutical compound for the prevention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Consumers increasingly prefer and seek functional beverages, which, given their characteristics, provide important bioactive compounds that help prevent and treat chronic diseases. Mead is a traditional fermented alcoholic beverage made from honey solution. The aging process of mead with oak chips is innovative and bestows functional characteristics to this beverage. Thus, in this study, we sought to develop and characterize a novel functional beverage by combining the health benefits of honey with the traditional aging process of alcoholic beverages in wood. Phenolic compounds, flavonoids, and antioxidant capacity were analyzed in mead using oak chips at different toasting levels and aged for 360 days. LC-ESI-QTOF-MS/MS was used to analyze the chemical profile of different meads. Over time, the aging process with oak chips showed a higher total phenolic and flavonoid content and antioxidant capacity. Eighteen compounds belonging to the classes of organic acids, phenolic acids, flavonoids, and tannins were identified in meads after 360 days. Our findings revealed that the addition of oak chips during aging contributed to p-coumaric, ellagic, abscisic, and chlorogenic acids, and naringenin, vanillin, and tiliroside significantly impacted the functional quality of mead. [ABSTRACT FROM AUTHOR]

Achyrocline flaccida aqueous extract was obtained by macerating wildflowers. The phytochemical profile present in the A. flaccida aqueous extract was elucidated by HPLC-ESI-MS/MS. Toxicity was evaluated in vitro by comet assay in peripheral blood mononuclear cells (PBMCs) and in vivo using Caenorhabditis elegans as a model. The antioxidant activity was also evaluated, and antimycobacterial activity was assessed by the broth microdilution method. The compounds present in the aqueous extract mainly belonged to the flavonoid class (89%). The concentrations that showed protective effects in C. elegans against oxidative stress and antimycobacterial activity had no toxic effects. The antimycobacterial activity test demonstrated that the concentration of 1,560 µg mL−1 inhibited the growth and eradication of the mycobacterial tested strains. Based on our findings, the A. flaccida aqueous extract presents a viable potential in developing new phytotherapeutic drugs against mycobacteria of clinical relevance. [ABSTRACT FROM AUTHOR]

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses. [ABSTRACT FROM AUTHOR]

Achyrocline flaccida (Weinm) DC. essential oil was obtained by hydrodistillation of wild flowers from southern Brazil. We explored, for the first time, the phytochemical composition, toxicity, resistance to oxidative stress in Caenorhabditis elegans, and antimycobacterial activities of A. flaccida essential oil. Twenty-four compounds were identified by GC-FID-MS and the major constituents identified were α-pinene (41.10%) and caryophyllene (30.52%). The essential oil showed no signs of genotoxicity in the comet assay and presented relevant antioxidant capacity since it prevented ROS production in the C. elegans model. Furthermore, the minimal inhibitory concentrations (MIC) results showed that M. abscessus, M. massiliense, and M. fortuitum had their growth inhibited by A. flaccida essential oil. Therefore, the essential oil of this plant is a promising alternative in the search for new compounds capable of decreasing oxidative stress and treating mycobacteriosis. [ABSTRACT FROM AUTHOR]

Abstract Background There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels. Methods Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL 160 mg/dL, n = 43). Results The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p Conclusions Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.