Search

Background: Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public health problem, a frequent cause of morbidity and disability for work. Some mechanisms of cell death are described as important tools in infectious processes. When apoptosis is blocked, RIPK (Receptor-interacting protein kinase) 3 dependent, a caspase-independent form of cell death, can limit the replication and spread of pathogens. Some molecules that mediate necroptosis include RIPK3 and have been extensively studied due to their signalling mechanism and pathological function. RIPK3 activates NLRP1 and NLRP3-mediated inflammasome formation. Caspase-1 has an important role in processing the cytokines ILß and IL18 to their active form. Such molecules are part of the inflammasome characterization, whose caspase-1-dependent activation promotes the death of pyroptotic cells and the secretion of proinflammatory cytokines. Knowledge about the mechanisms of pathogenmediated cell death can be useful for understanding of the pathogenesis of infections and inflammatory conditions. Objective: The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1ß, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining. Results: Our results on in situ expression of inflammasome elements and programmed cell death showed increased expression of IL-1ß, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The stem bark of Dilodendron bipinnatum Radlk. (Sapindaceae), a tree native to Pantanal of Mato Grosso, Brazil, popularly known as “mulher-pobre” (poor woman), has been historically used by the locals, after decoction and maceration, for the treatment of inflammatory conditions. We have recently shown that these preparations indeed possess anti-inflammatory properties, which are mediated by the inhibition of cell migration and the modulation of Th1 and Th2 cytokines. The NO pathway was not affected. Aim of the present study The aim of the present study was to further investigate the mechanisms responsible for the anti-inflammatory properties of the hydroethanolic extract of the stem bark of Dilodendron bipinnatum (HE Db ). Materials and methods HEDb was obtained by maceration of the stem bark of D. bipinnatum as previously described. The corresponding effects on a macrophage-like cell line, RAW 264.7, were investigated. The apoptosis of RAW 264.7 upon treatment with LPS, HEDb and N-acetyl- L -cysteine (NAC) was assessed by flow cytometry, using an Annexin V-PE kit. The production of inflammatory cytokines (TNF-α, IL-1β and IL-10) and PGE 2 were evaluated by ELISA, after cell challenge with LPS. The intracellular redox state and changes in mitochondrial membrane potential were also assessed by flow cytometry, using DCFH-DA and JC-1 as probes. The protein expression levels of MAPK p-p38, p-ERK, p-JNK, MKP-1 and COX-2 were analysed by western blotting. Nuclear translocation of NF-қB was assessed by immunofluorescence microscopy. The quantified results are presented as a nuclear:cytoplasmic ratio. Results LPS, HEDb and NAC did not appear to decrease the number of viable cells in comparison to control treatment. HEDb attenuated the production of pro-inflammatory cytokines (IL-1β and TNF-α) and PGE 2 induced by LPS but did not affect IL-10. The production of ROS was also inhibited by HEDb (1, 5 or 20 µg/mL), even at the lowest concentration; at 20 µg/mL, HEDb was more effective than NAC, which was used as a positive control (74.1% and 66.2% inhibition of LPS's effect, respectively). LPS induced an increase in ΔΨm (19.2%, p<0.001), while HEDb inhibited the change in ΔΨm (7.7% at 20 µg/mL, p<0.001). The results of western blotting showed that HEDb inhibited the expression of MAPK p-p38, p-JNK and COX-2, while the expression of MKP-1 was increased. p-ERK was not affected. LPS promoted the nuclear translocation of NF-қB p65 (67%, p<0.01) in RAW 264.7 cells, in comparison to baseline (33%). Pre-treatment with HEDb inhibited this translocation of NF-κB p65 (58% at 20 µg/mL, p<0.001). Conclusion: HEDb has a potent anti-inflammatory activity and acts on multiple targets and biological pathways of potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Purpose: Beneficial effects of green tea (GT) polyphenols against obesity have been reported. However, until this moment the molecular mechanisms of how green tea can modulate obesity and regulates fat metabolism, particularly in adipose tissue, remain poorly understood. The aim of this study was to evaluate the role of GT extract in the adipose tissue of obese animals and its effect on weight gain, metabolism and function (de novo lipogenesis and lipolysis), and the involvement of AMP-activated protein kinase (AMPK). Methods and results: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Here, we show that obese rats treated with GT showed a significant reduction in indicators of obesity such as hyperlipidemia, fat synthesis, body weight, and fat depots as compared to those treated with standard control diet. AMPK was induced in adipose tissue in rats that were treated with GT and likely restored insulin sensitivity, increased mRNA expression of GLUT4, reducing the concentrations of plasma and liver lipid content, also stimulating fatty acid oxidation in the same tissue. Importantly, repression of de novo lipogenesis in the adipose tissue, reduced lipid droplets in the liver, and the development of insulin resistance in diet-induced obese rats were accompanied by AMPK activation. Conclusion: Our study identified that metabolic changes caused by GT intake induced AMPK activation and modulate the expression of genes involved in metabolism, particularly in adipose tissue, thus offering a therapeutic strategy to combat insulin resistance, dyslipidemia, and obesity in rats. [ABSTRACT FROM AUTHOR]

In South America, particularly in the Northeastern regions of Brazil, Turnera subulata leaf extract is used as an alternative traditional medicine approach for several types of chronic diseases, such as diabetes, hypertension, chronic pain, and general inflammation. Despite its widespread use, little is known about the medicinal properties of the plants of this genus. In this study, we evaluate the antioxidant and anti-inflammatory of T. subulata leaf extract in an in vitro model of inflammation, using lipopolysaccharide-stimulated RAW-264.7 macrophage cell line. We observed that cotreatment with T. subulata leaf extract was able to reduce the oxidative stress in cells due to inflammatory response. More importantly, we observed that the leaf extract was able to directly modulate inflammatory response by altering activity of members of the mitogen-activated protein kinase pathways. Our results demonstrate for the first time that T. subulata have antioxidant and anti-inflammatory properties, which warrant further investigation of the medicinal potential of this species. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Methods: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI⋅kg-1) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min⋅d-1, 5 d⋅wk-1 for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1β, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor β levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. Results: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P <0.001), and transforming growth factor Β(P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. Conclusions: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/ Akt signaling. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effects of chia seed and chia oil on heat shock protein (HSP) and related parameters in diet-induced obese rats. Methods: Animals were divided in six groups: control, high-fat and high-fructose diet (HFF), and HFF with chia seed or chia oil in short (6-wk) and long (12-wk) treatments. Plasma indicators of glucose tolerance and liver damage, skeletal muscle expression of antioxidant enzymes, and proteins controlling oxidative energy metabolism were determined. The limit of significance was set at P < 0.05. Results: The HFF diet induced glucose intolerance, insulin resistance, oxidative stress, and altered parameters related to obesity complications. The consumption of chia seed or chia oil did not reduce body weight gain or abdominal fat accumulation. However, chia seed and chia oil in both treatments improved glucose and insulin tolerance. Chia oil in both treatments induced expression of HSP70 and HSP25 in skeletal muscle. Short treatment with chia seed increased expression of HSP70, but not HSP25. Chia oil in both treatments restored superoxide dismutase and glutathione peroxidase expression. Extended treatment with chia seed and short treatment with chia oil restored peroxisome proliferator-activated receptor-g coactivator-1α (PGC-1α) expression. Conclusion: Chia oil restored the antioxidant system and induced the expression of a higher number of proteins than chia seed. The present study demonstrated new properties and molecular mechanisms associated with the beneficial effects of chia seed and chia oil consumption in diet-induced obese rats. [ABSTRACT FROM AUTHOR]

Lippia sidoides is an aromatic shrub that grows wild in the northeastern region of Brazil. In local traditional medicine, the aerial portions of this species are used as anti-infectives, antiseptics, spasmolytics, sedatives, hypotensives, and anti-inflammatory agents. In this research, we evaluate the potential immunological properties of Lippia extract through in vitro analysis of its ability to modulate intracellular cyclic adenosine monophosphate (cAMP) levels and interleukin-10 (IL-10) production. These results show that Lippia extract increases intracellular cAMP through the inhibition of phosphodiesterase activity. They also demonstrate that Lippia extract increases IL-10 production in THP-1 monocytes through both an increase in intracellular cAMP and the activation of p38 MAPK. These results suggest that the Lippia-mediated inhibition of phosphodiesterase activity and the subsequent increase in intracellular cAMP may explain some of the biological activities associated with L. sidoides. In addition, the anti-inflammatory activity of L. sidoides may also be due, in part, to its ability to induce IL-10 production through the inhibition of cyclic nucleotide-dependent phosphodiesterase activity and by its activation of the p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

The global demand for sugarcane products, such as ethanol, is growing and requires a rapid increase in sugarcane productivity to meet the market needs. On the other hand, water deficit has been successively limiting production in the majority of Brazil and world producing areas. We aimed to assess the industrial quality components and productivity of transgenic sugarcane containing gene NPK1 (Nicotiana protein kinase 1) from tobacco, under with and without water deficit conditions. Two experiments were conducted: one with and another without water deficit using the following genotypes: Agrobacterium and biolistics transrformation methods and a control (no transgenic). The industrial quality parameters ((soluble solids (Brix), Pol, fiber content, apparent purity, reducing sugars (RS), total recoverable sugar (TRS)) and total sugars (TS) productivity were evaluated end of each cycle. The industrial quality components did not differ under normal cultivation. However, the total sugar production per unit area of plants with the NPK1 gene was favored, resulting in a 66% increased from control plants. Under water deficit, the insertion of NPK1 gene promoted improvement of industrial quality components (Brix, Pol, and TRS) and increased by 102% the total sugar production, raw material for ethanol production. The results suggest that the insertion of the NPK1 gene in sugarcane is a promising strategy to increased productivity both under normal conditions and water deficit conditions. They may also indicate a sustainable way to mitigate the increasing global climatic variations that severely affect sugarcane crop. • NPK1 from tobacco is known to improve abiotic stress tolerance in other crops. • We grew NPK1 -transgenic sugarcane under normal and drought conditions. • Under normal cultivation conditions it improved sugar production by 66%. • Under water deficit it increased total sugars production by 102%. • NPK1 increased the industrial quality components under water deficit. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The plant Cecropia pachystachya Trécul has been used in Brazilian folk medicine to treat hypertension, bladder and kidney inflammation and renal diseases. The aim of this study was to evaluate the potential of the aqueous fraction from the ethanolic extract of Cecropia pachystachya (FCP) in the management of hypertension, inflammation and progressive renal disease in rats submitted to 5/6 nephrectomy. Materials and methods Thirty male Wistar rats submitted to 5/6 nephrectomy (5/6 NE) were untreated (NE) or treated (NE+FCP) with the FCP (0.5 g/kg/day). The treatment started 15 days after surgery, and the rats were followed for a period of 60 days. Systolic blood pressure (SBP) and albuminuria were evaluated from 15–60 days after the surgical procedure. Function and estructural renal changes, TGF-β (transforming growth factor β), MCP-1 (monocyte chemoattractant protein-1) and nitric oxide (NO) urinary excretion were analyzed. Expression and activity of the renal enzymes arginase (ARG), angiotensin converting enzyme (ACE), and MAP kinase p-JNK expression also were analyzed. Results The nephrectomized rats developed progressive albuminuria and increased SBP that was less intense in the treated group. There was a reduction in the glomerular filtration rate (GFR) in the nephrectomized rats, which was attenuated by treatment with FCP extract. The treatment with FCP also attenuated the histological changes, reduced the expression and activity of renal arginase, the number of macrophages (ED-1 positive cells) and the p-JNK expression in the renal cortex of the rats submitted to 5/6 NE. The urinary excretion of TGF-β was less intense in the treated group and was associated with the reduction of the expression and activity of the renal arginase. Conclusions These results suggest that the reduction of renal arginase activity, p-JNK and TGF-β expression can explain the mechanism by which the treatment with C. pachystachya reduced the inflammation and improved renal function. This study presents the potential use of Cecropia pachystachya in the treatment of chronic renal diseases. [ABSTRACT FROM AUTHOR]

Aim of the study: Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglicemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle). Material and methods: Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals. Results: The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. Conclusions: Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction. [Copyright &y& Elsevier]

Abstract: Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs. [Copyright &y& Elsevier]