Bioactives of Melipona rufiventris Propolis: Exploring its Antimicrobial, Anti-Inflammatory, and Antioxidant Activities.

This study explores the potential of propolis, a resinous substance produced by bees, from Melipona rufiventris species. With its composition encompassing resin, wax, pollen, and soil, propolis holds historical significance in traditional medicine within tropical regions. This research is driven by the scarcity of information surrounding M. rufiventris propolis, prompting an investigation into its chemical constituents, in vivo toxicity, and antimicrobial, antioxidant, and anti-inflammatory properties. This exploration could potentially uncover novel applications for this natural product, bolstering both meliponiculture practices and the preservation of native bee populations. The propolis was sampled in Cabo Verde-MG and underwent ethanolic extraction to yield an extract (EEP) for analysis. Chemical assessments (Folin-Ciocalteau, and UHPLC-HRMS) revealed the presence of polyphenols, including flavonoids. The EEP demonstrated higher antimicrobial activity against Gram-positive bacteria and exhibited efficacy against multiresistant strains isolated from complex wounds. Synergistic interactions with commercial antibiotics were also observed. Furthermore, anti-inflammatory evaluations showcased the EEP's potential in reducing NF-kB activation and TNF-α release at non-toxic concentrations. Despite these promising biological activities, the EEP exhibited no antiproliferative effects and demonstrated safety in both the MTS assay and the G. mellonella model. Collectively, these findings highlight the M. rufiventris propolis extract as a valuable reservoir of bioactive compounds with multifaceted potential.

Paediatric sepsis survivors are resistant to sepsis-induced long-term immune dysfunction.

BACKGROUND AND PURPOSE: Sepsis-surviving adult individuals commonly develop immunosuppression and increased susceptibility to secondary infections, an outcome mediated by the axis IL-33/ILC2s/M2 macrophages/Tregs. Nonetheless, the long-term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis. EXPERIMENTAL APPROACH: Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. Likewise, sepsis-surviving mice were inoculated intranasally with Pseudomonas aeruginosa or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis-surviving patients were collected and the concentration of IL-33 and Tregs frequency were assessed. KEY RESULTS: In contrast to 6-week-old mice, 2-week-old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in 6-week-old but not 2-week-old post-septic mice. Moreover, impaired IL-33 production in 2-week-old post-septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in 2-week-old mice. Clinically, adults but not paediatric post-septic patients exhibited higher counts of Tregs and seral IL-33 levels. CONCLUSION AND IMPLICATIONS: These findings demonstrate a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis.

Purple tea (Camellia sinensis var. assamica) leaves as a potential functional ingredient: From extraction of phenolic compounds to cell-based antioxidant/biological activities.

A statistical optimization study was used to maximize the extraction of bioactive compounds and antioxidant activity from green tea derived from purple leaves of Camellia sinensis var. assamica. Simultaneous optimization was applied, and a combination of 60 °C, 15 min, and a mass-solvent ratio of 1 g of dehydrated purple leaves to 62.3 mL of an ethanol/citric acid solution, were determined as the ideal extraction conditions. The optimized extract of purple tea leaves (OEPL) contained showed stability in relation to variations in pH, and lyophilized OEPL exerted cytotoxic and antiproliferative effects against cancerous cells (A549 and HCT8), demonstrated antimicrobial activity towards Listeria monocytogenes (ATCC 7644), Staphylococcus aureus (ATCC 13565) and Staphylococcus epidermidis (ATCC 12288), inhibition of α-amylase and α-glycosidase enzymes and reduced the release of pro-inflammatory cytokines (TNF-α, CXCL2/MIP-2, and IL-6) in lipopolysaccharides-stimulated RAW 264.7 macrophages. Thus, our results provide a broad assessment of the bioactivity of "green" extracts obtained by a simple and low-cost process using non-toxic solvents, and they have the potential to be used for technological applications.

Phenolic Profile and the Antioxidant, Anti-Inflammatory, and Antimicrobial Properties of Açaí (Euterpe oleracea) Meal: A Prospective Study.

The mechanical extraction of oils from Brazilian açaí (Euterpe oleracea Mart) produces significant amounts of a byproduct known as "meal", which is frequently discarded in the environment as waste material. Nevertheless, plant byproducts, especially those from oil extraction, may contain residual polyphenols in their composition and be a rich source of natural bioactive compounds. In this study, the phenolic composition and in vitro biological properties of a hydroethanolic açaí meal extract were elucidated. The major compounds tentatively identified in the extract by high-resolution mass spectrometry were anthocyanins, flavones, and flavonoids. Furthermore, rhamnocitrin is reported in an açaí byproduct for the first time. The extract showed reducing power and was effective in scavenging the ABTS radical cation (820.0 µmol Trolox equivalent∙g-1) and peroxyl radical (975.7 µmol Trolox equivalent∙g-1). NF-κB activation was inhibited at 10 or 100 µg∙mL-1 and TNF-α levels were reduced at 100 µg∙mL-1. However, the antibacterial effects against ESKAPE pathogens was not promising due to the high concentration needed (1250 or 2500 µg∙mL-1). These findings can be related to the diverse polyphenol-rich extract composition. To conclude, the polyphenol-rich extract obtained from açaí meal showed relevant biological activities that may have great applicability in the food and nutraceutical industries.

Inajá oil processing by-product: A novel source of bioactive catechins and procyanidins from a Brazilian native fruit.

Agro-industrial activities generate large amounts of solid residues, which are generally discarded or used as animal feed. Interestingly, some of these by-products could serve as natural sources of bioactive compounds with great potential for industrial exploitation. This study aimed to optimize the extraction of phenolic antioxidants from the pulp residue (oil processing by-product) of inajá (Maximiliana maripa, a native species found in the Brazilian Amazon). The antioxidant properties of the optimized extract and its phenolic profile by high-resolution mass spectrometry (LC-ESI-QTOF-MS) were further determined. Central composite rotatable design and statistical analysis demonstrated that the temperature of 70 °C and 50% (v/v) ethanol concentration improved the extraction of phenolic compounds with antioxidant properties. The optimized extract also showed scavenging activity against the ABTS radical cation and reactive oxygen species (ROS; peroxyl and superoxide radical, and hypochlorous acid). Moreover, the optimized extract was able to reduce NF-κB activation and TNF-α release, which are modulated by ROS. Flavan-3-ols were the major phenolics present in the optimized extract. Collectively, our findings support the use of inajá cake as a new source of bioactive catechins and procyanidins. This innovative approach adds value to this agro-industrial by-product in the functional food, nutraceutical, pharmaceutical, and/or cosmetic industries and complies with the circular economy agenda.

Simulated gastrointestinal digestion of Brazilian açaí seeds affects the content of flavan-3-ol derivatives, and their antioxidant and anti-inflammatory activities.

Açaí seeds (Euterpe oleracea Mart.) are the major residue generated during industrial extraction of açaí fruit pulp - a popular and typical Amazon fruit rich in bioactive compounds and nutrients. In this study, we investigated the bioaccessibility of an açaí seed extract using an in vitro simulated gastrointestinal digestion model. Catechin, epicatechin and procyanidins B1 and B2 were identified and quantified in the açaí seed extract and monitored by HPLC-DAD through the digestion phases. Bioaccessibility of these flavan-3-ols and deactivation of reactive oxygen species decreased after the intestinal phase, except for peroxyl radical (ROO●). RAW 264.7 macrophages treated either with the digested or undigested açaí seed extract showed reduced NF-κB activation and TNF-α levels, even following gastrointestinal digestion. Thus, the ROO● scavenging capacity and anti-inflammatory activity of the extract were found to be still remarkable after digestion, suggesting that açaí seeds could be explored as a source of bioactive compounds for functional foods, cosmetic or pharmaceutical purposes.

Phenolic profile and potential beneficial effects of underutilized Brazilian native fruits on scavenging of ROS and RNS and anti-inflammatory and antimicrobial properties.

Brazilian native fruits (BNF) have aroused interest of researchers and consumers for their great human health benefits. In this study, five BNF (Byrsonima lancifolia, Campomanesia phaea, Jacaratia spinosa, Solanum alternatopinnatum and Acnistus arborescens) were tested for their polyphenolic compounds by LC-ESI-MS/MS, reactive species deactivation (ROO˙, O2˙-, HOCl and NO˙), anti-inflammatory properties in vivo, and in vitro antimicrobial activity - with determination of putative mechanism(s) of action. Eighty-one polyphenols were identified, which exhibited a significant capacity to deactivate both ROS and RNS. C. phaea extract had the highest capacity to scavenge ROO˙ (68.94 µmol TE per g), O2˙- (IC50: 575.36 µg mL-1) and NO˙ (IC50: 16.96 µg mL-1), which may be attributed to the presence of ellagitanins. B. lancifolia decreased neutrophil influx into the peritoneal cavity of mice by 50% as compared to carrageenan and reduced Candida albicans biofilm viability by 3 log10 possibly due to complexation with cell membrane ergosterol. In summary, the BNF presented herein are good sources of bioactive compounds with positive effects on deactivation of biological reactive species, as well as with anti-inflammatory and antimicrobial activities, which can be altogether highly beneficial to human health.

Anti-inflammatory and antioxidant potential, in vivo toxicity, and polyphenolic composition of Eugenia selloi B.D.Jacks. (pitangatuba), a Brazilian native fruit.

Brazilian native fruits are a rich source of polyphenolic compounds that can act as anti-inflammatory and antioxidant agents. Here, we determined the polyphenolic composition, anti-inflammatory mechanism of action, antioxidant activity and systemic toxicity in Galleria mellonella larvae of Eugenia selloi B.D.Jacks. (synonym Eugenia neonitida Sobral) extract (Ese) and its polyphenol-rich fraction (F3) obtained through bioassay-guided fractionation. Phenolic compounds present in Ese and F3 were identified by LC-ESI-QTOF-MS. The anti-inflammatory activity of Ese and F3 was tested in vitro and in vivo through NF-κB activation, cytokine release and neutrophil migration assays. The samples were tested for their effects against reactive species (ROO•, O2•-, HOCl and NO•) and for their toxicity in Galleria mellonella larvae model. The presence of hydroxybenzoic acid, ellagitannins and flavonoids was identified. Ese and F3 reduced NF-κB activation, cytokine release and neutrophil migration, with F3 being three-fold more potent. Overall, F3 exhibited strong antioxidant effects against biologically relevant radicals, and neither Ese nor F3 were toxic to G. mellonella larvae. In conclusion, Ese and F3 revealed the presence of phenolic compounds that decreased the inflammatory parameters evaluated and inhibited reactive oxygen/nitrogen species. E. selloi is a novel source of bioactive compounds that may provide benefits for human health.

Anti-inflammatory and anti-Candida Effects of Brazilian Organic Propolis, a Promising Source of Bioactive Molecules and Functional Food.

Brazilian organic propolis (BOP) is an unexplored Brazilian propolis that is produced organically and certified according to international legislation. Our results showed that BOP has strong anti-inflammatory effects and acts by reducing nuclear factor κB activation, tumor necrosis factor α release, and neutrophil migration. In addition, BOP6 exhibited antifungal activity on planktonic and biofilm cultures of Candida albicans, Candida glabrata, Candida tropicalis, Candida krusei, and Candida parapsisolis and reduced in vitro yeast cell adhesion to human keratinocytes at sub-inhibitory concentrations. BOP demonstrated significantly low toxicity in Galleria melonella larvae at antifungal doses. Lastly, a chemical analysis revealed the presence of caffeoyltartaric acid, 3,4-dicaffeoylquinic acid, quercetin, and gibberellins A7, A9, and A20, which may be responsible for the biological properties observed. Thus, our data indicate that BOP is a promising source of anti-inflammatory and antifungal molecules that may be used as a functional food.

Camu-camu seed (Myrciaria dubia) - From side stream to anantioxidant, antihyperglycemic, antiproliferative, antimicrobial, antihemolytic, anti-inflammatory, and antihypertensive ingredient.

Camu-camu (Myrciaria dubia) seeds are discarded without recovering the bioactive compounds. The main aim of the present work was to optimise the solvent mixture to extract higher total phenolic content and antioxidant capacity of camu-camu seeds. The optimised solvent system increased the extraction of phenolic compounds, in which vescalagin and castalagin were the main compounds. The optimised extract displayed antioxidant capacity measured by different chemical and biological assays, exerted antiproliferative and cytotoxic effects against A549 and HCT8 cancer cells, antimicrobial effects, protected human erythrocytes against hemolysis, inhibited α-amylase and α-glucosidase enzymes and presented in vitro antihypertensive effect. Additionally, the optimized extract inhibited human LDL copper-induced oxidation in vitro and reduced the TNF-α release and NF-κB activation in macrophages cell culture. Thus, the use of camu-camu seed showed to be a sustainable way to recover bioactive compounds with in vitro functional properties.

Optimizing the potential bioactivity of isoflavones from soybeans via ultrasound pretreatment: Antioxidant potential and NF-κB activation.

Soybean consumption has been associated with health benefits. However, the effect of ultrasound (US) soybean pretreatment in terms of potential health benefits has not been investigated so far. Accordingly, the total phenolic content (TPC) and the total aglycone content (TAC) were optimized using the Box-Behnken design. Contrasting samples regarding isoflavones aglycones and TPCs were screened for their antioxidant and anti-inflammatory potentials using RAW 264.7 macrophages. US pretreated soybeans (55°C, 15 min, and 24 W/cm2 ) showed greater TPC and TAC compared to the control and this translated to higher antiradical activity and reduction of nuclear factor kappa B (NF-κB) activation. The concentration of genistein in treated soybeans increased by 95%. Furthermore, US pretreated soybeans rendered phenolic extracts that reduced the NF-κB activation by 86%. Therefore, this contribution demonstrates the beneficial effects of US pretreatment of soybeans, which provides a better feedstock for the functional food industry. PRACTICAL APPLICATIONS: Soybeans can be consumed as such or used as a feedstock to produce soy yogurt, fermented soymilk, tofu, and protein concentrate, among others. The greatest bioavailability of isoflavones compared to other flavonoids has recently been highlighted, and this has been explained by the relatively moderate lipophilicity of isoflavones as aglycones. The present contribution supports the use of US pretreatment of soybeans to obtain a feedstock with improved contents of isoflavones as aglycones. We have confirmed that phenolic extracts obtained from the US pretreated samples showed higher bioactivity as radical scavengers and by reducing the activation of nuclear factor kappa B (NF-κB) in a cell model, which is mediated by oxidative species. The clinical importance of NF-κB activation is derived mainly from its role in inflammatory responses. Therefore, our investigation may have a practical application in the procurement of soybean products and/or ingredients with improved functional properties related to their health benefits.

Is Chickpea a Potential Substitute for Soybean? Phenolic Bioactives and Potential Health Benefits.

Legume seeds are rich sources of protein, fiber, and minerals. In addition, their phenolic compounds as secondary metabolites render health benefits beyond basic nutrition. Lowering apolipoprotein B secretion from HepG2 cells and decreasing the level of low-density lipoprotein (LDL)-cholesterol oxidation are mechanisms related to the prevention of cardiovascular diseases (CVD). Likewise, low-level chronic inflammation and related disorders of the immune system are clinical predictors of cardiovascular pathology. Furthermore, DNA-damage signaling and repair are crucial pathways to the etiology of human cancers. Along CVD and cancer, the prevalence of obesity and diabetes is constantly increasing. Screening the ability of polyphenols in inactivating digestive enzymes is a good option in pre-clinical studies. In addition, in vivo studies support the role of polyphenols in the prevention and/or management of diabetes and obesity. Soybean, a well-recognized source of phenolic isoflavones, exerts health benefits by decreasing oxidative stress and inflammation related to the above-mentioned chronic ailments. Similar to soybeans, chickpeas are good sources of nutrients and phenolic compounds, especially isoflavones. This review summarizes the potential of chickpea as a substitute for soybean in terms of health beneficial outcomes. Therefore, this contribution may guide the industry in manufacturing functional foods and/or ingredients by using an undervalued feedstock.

Should we ban total phenolics and antioxidant screening methods? The link between antioxidant potential and activation of NF-κB using phenolic compounds from grape by-products.

Free radical imbalance is associated with several chronic diseases. However, recent controversies have put in check the validity of colorimetric methods to screen the functionality of polyphenols. Therefore, in this study two antioxidant methods, based on chemical reactions, were tested for their ability in anticipating the reduction of the activation of NF-κB using LPS-activated RAW 264.7 macrophages, selected as a biological model. Grape processing by-products from winemaking showed higher total phenolic content (TPC), antioxidant capacity towards peroxyl radical (31.1%) as well as reducing power (39.5%) than those of grape juice by-products. The same trend was observed when these samples were tested against LPS-activated RAW 264.7 macrophages by reducing the activation NF-κB. Feedstocks containing higher TPC and corresponding ORAC and FRAP results translated to higher reduction in the activation of NF-κB (36.5%). Therefore, this contribution demonstrates that colorimetric methods are still important screening tools owing their simplicity and widespread application.

DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A2A receptor.

Cannabidiol (CBD) is a natural compound with psychoactive therapeutic properties well described. Conversely, the immunological effects of CBD are still poorly explored. In this study, the potential anti-inflammatory effects and underlying mechanisms of CBD and its analog Dimethyl-Heptyl-Cannabidiol (DMH-CBD) were investigated using RAW 264.7 macrophages. CBD and DMH-CBD suppressed LPS-induced TNF production and NF-kB activity in a concentration-dependent manner. Both compounds reduced the NF-kB activity in a µM concentration range: CBD (IC50 = 15 µM) and DMH-CBD (IC50 = 38 µM). However, the concentrations of CBD that mediated NF-kB inhibition were similar to those that cause cytotoxicity (LC50 = 58 µM). Differently, DMH-CBD inhibited the NF-kB activation without cytotoxic effects at the same concentrations, although it provokes cytotoxicity at long-term exposure. The inhibitory action of the DMH-CBD on NF-kB activity was not related to the reduction in IkBα degradation or either p65 (NF-kB) translocation to the nucleus, although it decreased p38 MAP kinase phosphorylation. Additionally, 8-(3-Chlorostyryl) caffeine (CSC), an A2A antagonist, reversed the effect of DMH-CBD on NF-kB activity in a concentration-dependent manner. Collectively, our results demonstrated that CBD reduces NF-kB activity at concentrations intimately associated with those that cause cell death, whereas DMH-CBD decreases NF-kB activity at non-toxic concentrations in an A2A receptor dependent-manner.

Opinion on the Hurdles and Potential Health Benefits in Value-Added Use of Plant Food Processing By-Products as Sources of Phenolic Compounds.

Plant foods, their products and processing by-products are well recognized as important sources of phenolic compounds. Recent studies in this field have demonstrated that food processing by-products are often richer sources of bioactive compounds as compared with their original feedstock. However, their final application as a source of nutraceuticals and bioactives requires addressing certain hurdles and challenges. This review discusses recent knowledge advances in the use of plant food processing by-products as sources of phenolic compounds with special attention to the role of genetics on the distribution and biosynthesis of plant phenolics, as well as their profiling and screening, potential health benefits, and safety issues. The potentialities in health improvement from food phenolics in animal models and in humans is well substantiated, however, considering the emerging market of plant food by-products as potential sources of phenolic bioactives, more research in humans is deemed necessary.

Bioprospection of Eugenia brasiliensis, a Brazilian native fruit, as a source of anti-inflammatory and antibiofilm compounds.

The anti-inflammatory and antibiofilm activities as well as toxicity and chemical profile of Eugenia brasiliensis pulp extract (EBE), were evaluated. EBE chemical profile and phenolic content were determined by LC-MS/MS. EBE was tested for its in vitro and in vivo anti-inflammatory activity, including TNF-α release, NF-кB activation, neutrophil migration and paw edema. The MIC/MBC and antibiofilm activities were tested against methicillin sensitive and resistant Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, Streptococcus mutans, and Lactobacillus acidophilus. EBE acute toxicity was evaluated in Galleria mellonella and RAW 264.7 macrophage. EBE total phenolic content was 389.88 ±â€¯3.48 mg GAE/g with identified polyphenols. EBE decreased TNF-α release in vivo and in vitro, NF-кB activation, neutrophil influx into peritoneal cavity, and it showed maximal inhibition of paw edema after 2 h. MIC of EBE ranged from 62.5-500 µg/mL while MBC values were >500 µg/mL, with a decrease in L. acidophilus biofilm formation. EBE showed negligible toxicity in larvae and macrophage cells. Our findings open new perspectives concerning EBE application as source of anti-inflammatory and antibiofilm molecules as a functional food, pharmaceutical lead or agribusiness commodity.

Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.

Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a unique Apis melifera type of propolis botanically originated from Dalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole-genome expression in human tumor cells, particularly cancer-related target proteins. HeLa cells were exposed to the compounds at IC20 and genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC20  = 214.7 µM) reduced the expression of genes enrolled with the alpha tubulin (fold -3.7), tubulin in microtubules (fold -3.7), and histone h3 (fold = -3.03), and that treatment with neovestitol (IC20  = 102.91 µM) downregulated prostaglandin E synthase gene (fold = -3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non-clinical, and clinical validation of the findings presented herein is needed.

Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis.

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations.

Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis.

South Brazilian organic propolis (OP), which has never been studied before, was assessed and its chemical composition, scavenging potential of reactive oxygen species, antimicrobial and anti-inflammatory activities are herein presented. Based on the chemical profile obtained using HPLC, OP was grouped into seven variants (OP1-OP7) and all of them exhibited high scavenging activity, mainly against superoxide and hypochlorous acid species. OP1, OP2, and OP3 had the smallest minimal inhibitory concentration (MIC) against Gram-positive bacteria Streptococcus mutans, Streptococcus oralis, and Streptococcus aureus (12.5-100 µg/mL). OP1, OP2, OP3, and OP4 were more effective against Pseudomonas aeruginosa (Gram-negative), with MIC values ranging from 100 to 200 µg/mL. OP6 showed anti-inflammatory activity by decreasing NF-kB activation and TNF-α release in RAW 264.7 macrophages, and expressing the NF-κB-luciferase reporter stable gene. Therefore, south Brazilian OP can be considered an excellent source of bioactive compounds with great potential of application in the pharmaceutical and food industry.