The antioxidant and anti-inflammatory properties of lycopene in mice lungs exposed to cigarette smoke.

Lycopene is a carotenoid with knownantioxidant and anti-inflammatory properties.Weaimed to evaluate the in vitro and in vivo effects of lycopene on reducing the redox imbalance and inflammation induced by cigarette smoke (CS). For the in vitro study, J774A.1 (macrophages) cells were incubated in the presence of 0.5, 1.0, 2.0, 4.0, 8.0, 10.0 and 25 ?Mof lycopene for 3, 6 and 24 h or in the presence of 0.1%, 0.25%, 0.5%, 0.625%, 1.25%, 2.25%, 5% and 10% cigarette smoke extract (CSE) for 3, 6 and 24 h to assess cell viability and measurement of intracellular reactive oxygen species (ROS). For the in vivo study, 40 micewere divided into 5 groups: a control exposed to ambient air (CG), a vehicle-control group that received 200 ?l of sunflower oil by orogastric gavage, a group exposed to CS and two groups administered lycopene (diluted in sunflower oil) at doses of either 25 or 50 mg/kg/day prior to exposure to CS (LY25+CS and LY50+CS). The total treatment time lasted 5 days. A cell viability decreasewas observed at 10- and 25-?Mconcentrations of lycopene in 3, 6 and 24 h compared with CG. Therewas an increase ofROS production in 24 h in CS compared with CG. Lycopene concentrations of 1 ?Mand 2 ?Mwere able to reduce the production of ROS in 24 h comparedwith CS. In the bronchoalveolar lavage fluid, the total number of leukocytes increased in the CS group compared with the control groups (CG). Administrationwith lycopene at the highest dose suppressed this CS-induced increase in leukocytes. Lipid peroxidation and DNA damage increased in the CS group comparedwith that in the controls, and this increase was suppressed by lycopene at the highest dose. In contrast, superoxide dismutase activity decreased in the CS group compared with that in the controls. Catalase activity also increased in the CS group compared with that in both control groups, and this increase was suppressed in LY25+CS and LY50+CS. There was an increase in the levels of tumor necrosis factor-?, interferon-? and interleukin-10 after exposure to CS, and these effects were suppressed by both doses of lycopene. These data elucidate the role of lycopene as an antioxidant and anti-inflammatory agent in these two models of short-term exposure to CS

Baccharis trimera (Carqueja) Improves metabolic and redox status in an experimental model of type 1 diabetes.

Diabetes mellitus is a metabolic disorder that causes severe complications due to the increased oxidative stress induced by disease. Many plants are popularly used in the treatment of diabetes, e.g., Baccharis trimera (carqueja). The aim of this study was to explore the potential application of the B. trimera hydroethanolic extract in preventing redox stress induced by diabetes and its hypoglycemic properties. Experiments were conducted with 48 female rats, divided into 6 groups, named C (control), C600 (control + extract 600 mg/kg), C1200 (control + extract 1200 mg/kg), D (diabetic), D600 (diabetic + 600 mg/kg), and D1200 (diabetic + 1200 mg/kg). Type 1 diabetes was induced with alloxan, and the animals presented hyperglycemia and reduction in insulin and body weight. After seven days of experimentation, the nontreated diabetic group showed changes in biochemical parameters (urea, triacylglycerol, alanine aminotransferase, and aspartate aminotransferase) and increased carbonyl protein levels. Regarding the antioxidant enzymes, an increase in superoxide dismutase activity was observed but in comparison a decrease in catalase and glutathione peroxidase activity was noted which suggests that diabetic rats suffered redox stress. In addition, the mRNA of superoxide dismutase, catalase, and glutathione peroxidase enzymes were altered. Treatment of diabetic rats with B. trimera extract resulted in an improved glycemic profile and liver function, decreased oxidative damage, and altered the expression of mRNA of the antioxidants enzymes. These results together suggest that B. trimera hydroethanolic extract has a protective effect against diabetes

Baccharis trimera inibe a produ??o de esp?cies reativas de oxig?nio atrav?s da via de sinaliza??o da PKC e NADPH oxidase em c?lulas SK Hep-1.

Programa de P?s-Gradua??o em Ci?ncias Biol?gicas. N?cleo de Pesquisas em Ci?ncias Biol?gicas, Pr?-Reitoria de Pesquisa de P?s Gradua??o, Universidade Federal de Ouro Preto.Baccharis trimera, popularmente conhecida como "carqueja", ? uma planta nativa sul-americana que possui uma alta concentra??o de compostos fen?licos e, portanto, alto potencial antioxidante. Apesar do potencial antioxidante de B. trimera descrito na literatura, n?o existem relatos sobre as vias de sinaliza??o envolvidas neste processo. A enzima NADPH oxidase ? uma fonte importante na produ??o de esp?cies reativas de oxig?nio (ERO) em condi??es patol?gicas, como no c?ncer, no diabetes e em processos inflamat?rios. Esta enzima ? ativada por meio de diferentes moduladores, entre os quais destaca-se a prote?na cinase C (PKC), que fosforila a subunidade p47phox da NADPH oxidase, como um contribuinte para a ativa??o do complexo enzim?tico e a consequente gera??o de ERO. Com base nestas informa??es, o objetivo do presente estudo foi avaliar a composi??o fitoqu?mica dos extratos aquoso e hidroetan?lico de Baccharis trimera bem como a influ?ncia destes extratos na modula??o de ERO e na via de sinaliza??o da PKC e NADPH oxidase em c?lulas de hepatocarcinoma humano (SK Hep-1). No presente estudo, a quercetina e a rutina foram utilizadas como controles positivos, pois o efeito antioxidante destes flavonoides tem sido bem estabelecido, sendo estes compostos j? identificados em extratos de B. trimera. No extrato hidroetan?lico foram identificados cinco flavonoides enquanto no extrato aquoso foram identificados tr?s flavonoides por CLAE-EM. A atividade antioxidante in vitro por DPPH tamb?m foi avaliada e os resultados demonstraram que o extrato hidroetan?lico possui um maior potencial em sequestrar o radical DPPH bem como uma maior quantidade de compostos fen?licos em compara??o ao extrato aquoso. Em rela??o ? viabilidade celular, observamos que o extrato hidroetan?lico de B. trimera manteve acima de 70% a porcentagem de c?lulas vi?veis, entretanto em 24 e 48 horas de incuba??o houve uma redu??o da viabilidade (<70%) em concentra??es iguais ou superiores a 25?gmL-1. Em rela??o ao extrato aquoso observamos que a porcentagem de c?lulas vi?veis foi mantida acima de 70% em 12, 24 e 48 de incuba??o. Em rela??o a produ??o de esp?cies reativas foi observado que os extratos de B. trimera (aquoso e hidroetan?lico) diminu?ram os n?veis de ERO em c?lulas SK Hep-1 n?o estimuladas. N?veis reduzidos de ERO tamb?m foram observados nas c?lulas tratadas com quercetina e rutina. Os resultados mostraram que as c?lulas estimuladas com PMA / ionomicina (ativadores de PKC) tiveram um aumento significativo na produ??o de ERO, e esta produ??o voltou aos n?veis basais ap?s tratamento com o DPI (inibidor da NADPH oxidase). O extrato hidroetan?lico de B. trimera e quercetina, mas n?o o extrato aquoso e a rutina, modularam a produ??o de ERO atrav?s da inibi??o da express?o e atividade da prote?na PKC e tamb?m atrav?s da redu??o da fosforila??o da subunidade p47phox da enzima NADPH oxidase. Em conjunto, estes resultados sugerem um mecanismo potencial de a??o de B. trimera na inibi??o da produ??o de ERO atrav?s da via de sinaliza??o da PKC/NADPH oxidase.Baccharis trimera, popularly known as "carqueja" is a native South American plant having high concentration of phenolic compounds and therefore high potential antioxidant. Although the antioxidant potential of B. trimera described in the literature there are no reports on the signaling pathways involved in this process. The NADPH oxidase is a major source in production of reactive oxygen species (ROS) in pathological conditions such as cancer, diabetes and inflammation. This enzyme is activated by different modulators, among which we highlight protein kinase C (PKC), which phosphorylates p47phox subunit of NADPH oxidase, as a contributor to the activation of the enzyme complex and the subsequent generation of ROS . Based on this information, the aim of this study was to evaluate the phytochemical composition of aqueous and hydroethanolic extracts of Baccharis trimera and the influence of these extracts on ROS modulation induced by PKC signaling pathway in human hepatocellular carcinoma cells (SK-Hep 1). In the present study, quercetin and rutin were used as positive controls, since the antioxidant effect of these flavonoids have been well established, and these compounds have been identified in B. trimera extracts. In hydrethanolic extract five flavonoids were identified, and in the aqueous extract identified three flavonoids by CLAE-MS. The antioxidant activity in vitro was also evaluated by DPPH and the results demonstrated that the hydroethanolic extract has a higher potential scavenger the DPPH radical as well as a greater quantity of phenolic compounds as compared to aqueous extract. About cell viability, we observed that the hydroethanolic extract of B. trimera maintained above 70% of viable cells, however at 24 and 48 hours of incubation there was a reduction of viability (<70%) in concentrations equal to or greater than 25?gmL-1. About aqueous extract we found that the percentage of viable cells was maintained above 70% at 12, 24 and 48 of incubation. It was observed that extracts of B. trimera (aqueous and hydroethanolic) decreased ROS levels in the SK-Hep 1 cells unstimulated. Reduced levels of ROS were also observed in cells treated with quercetin and rutin. The results showed that cells stimulated with PMA / ionomycin (PKC activators) had a significant increase in ROS production and this production returned to basal levels after treatment with DPI (NADPH oxidase inhibitor). The B. trimera hydroethanolic extract and quercetin, but not the aqueous extract and rutin, modulate the production of ROS by inhibiting the expression and activity of PKC protein and downregulation p47phox phosphorilation. Together, these results suggest a potential mechanism of inhibition by B. trimera in ROS production by PKC/NADPH oxidase signaling pathway

Lycopene inhibits reactive oxygen species production in SK-Hep-1 cells and attenuates acetaminophen-induced liver injury in C57BL/6 mice.

Our aim was to investigate the antioxidant potential of lycopene in different experimental liver models: in vitro, to evaluate the influence of lycopene on reactive oxygen species (ROS) production mediated by the PKC pathway and in vivo, to evaluate the protective effects of lycopene in an experimental model of hepatotoxicity. The in vitro study assessed the lycopene antioxidant potential by the quantification of ROS production in SK-Hep-1 cells unstimulated or stimulated by an activator of the PKC pathway. The role of NADPH oxidase was evaluated by measuring its inhibition potential using an inhibitor of this enzyme. In the in vivo study, male C57BL/6 mice received lycopene (10 or 100 mg/kg by oral gavage) and 1 h later, acetaminophen (APAP) (500 mg/kg) was administrated. Lycopene decreased ROS production in SK-Hep- 1 cells through inhibition of NADPH oxidase, brought about in the PKC pathway. Lycopene improved hepatotoxicity acting as an antioxidant, reduced GSSG and regulated tGSH and CAT levels, reduced oxidative damage primarily by decreasing protein carbonylation, promoted the downregulation of MMP- 2 and reduced areas of necrosis improving the general appearance of the lesion in C57BL/6 mice. Lycopene is a natural compound that was able to inhibit the production of ROS in vitro and mitigate the damage caused by APAP overdose in vivo

Baccharis trimera protects against ethanol induced hepatotoxicity in vitro and in vivo.

Ethnopharmacological relevance: Baccharis trimera has been traditionally used in Brazil to treat liver diseases. Aim of the study: To evaluate the protective effect of Baccharis trimera in an ethanol induced hepatotoxicity model. Materials and methods: The antioxidant capacity was evaluated in vitro by the ability to scavenged the DPPH radical, by the quantification of ROS, NO and the transcription factor Nrf2. Hepatotoxicity was induced in animals by administration of absolute ethanol for 2 days (acute) or with ethanol diluted for 28 days (chronic). The biochemical parameters of hepatic function (ALT and AST), renal function (urea and creatinine) and lipid profile (total cholesterol, triglycerides and HDL) were evaluated. In addition to antioxidant defense (SOD, catalase, glutathione), oxidative damage markers (TBARS and carbonylated protein), MMP-2 activity and liver histology. Results: Baccharis trimera promoted a decrease in ROS and NO, and at low concentrations promoted increased transcription of Nrf2. In the acute experiment it promoted increase of HDL, in the activity of SOD and GPx, besides diminishing TBARS and microesteatosis. Already in the chronic experiment B. trimera improved the hepatic and renal profile, decreased triglycerides and MMP-2 activity, in addition to diminishing microesteatosis. Conclusion: We believe that B. trimera action is possibly more associated with direct neutralizing effects or inhibition of reactive species production pathways rather than the modulation of the antioxidant enzymes activity. Thus it is possible to infer that the biological effects triggered by adaptive responses are complex and multifactorial depending on the dose, the time and the compounds used

Annato extract and ?-carotene modulate the production of reactive oxygen species/nitric oxide in neutrophils from diabetic rats.

Annatto has been identified asecarotenoids that havetantioxidative effects. It is well known that one of the key elements in the development of diabetic complications is oxidative stress. The immune system is especially vulnerable to oxidative damage because many immune cells, such as neutrophils, produce reactive oxygen species and reactive nitrogen species as part of the body?s defense mechanisms to destroy invading pathogens. Reactive oxygen species/reactive nitrogen species are excessively produced by active peripheral neutrophils, and may damage essential cellular components, which in turn can cause vascular complications in diabetes. The present study was undertaken to evaluate the possible protective effects of annatto on the reactive oxygen species and nitric oxide (NO) inhibition in neutrophils from alloxan-induced diabetic rats. Adult female rats were divided into six groups based on receiving either a standard diet with or without supplementation of annatto extract or beta carotene. All animals were sacrificed 30 days after treatment and the neutrophils were isolated using two gradients of different densities. The reactive oxygen species and NO were quantified by a chemiluminescence and spectrophotometric assays, respectively. Our results show that neutrophils from diabetic animals produce significantly more reactive oxygen species and NO than their respective controls and that supplementation with beta carotene and annatto is able to modulate the production of these species. Annatto extract may have therapeutic potential for modulation of the balance reactive oxygen species/NO induced by diabetes

Vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats.

Background and Aims. It is believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus. Several strategies have been developed with the objective of minimizing diabetic complications. Among these, inhibitors of dipeptidyl peptidase-IV (DPP-IV), which act by blocking degradation of incretin hormones, glucagon-like peptide hormone (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), have been the focus of many studies. It is known that, among the effects of incretins, we highlight its insulinotropic and cytoprotective effects on pancreatic b-cells. The objective of this study was to evaluate the possible protective effects of treatment with vildagliptin, a DPP-IV inhibitor, in b-cells in an experimental model of type 1 diabetes induced by streptozotocin (STZ). Methods. Rats were treated for 4 weeks with vildagliptin at concentrations of 5 and 10 mg/kg. In order to observe the pancreatic damage and the possible protective effects of vildagliptin treatment, we measured stress markers TBARS and protein carbonyl, antioxidant enzymes SOD and catalase, and analyzed pancreatic histology. Results. The treatment was effective in modulating stress in pancreatic tissue, both by reducing levels of stress markers as well as by increasing activity of SOD and catalase. After analyzing the pancreatic histology, we found that vildagliptin was also able to preserve islets and pancreatic b-cells, especially at the concentration of 5 mg/kg. Conclusion. Thus, our results suggest that vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. However, to evaluate the real potential of this medication in type 1 diabetes, further studies are needed

Baccharis trimera inhibits reactive oxygen species production through PKC and down-regulation p47phox phosphorylation of NADPH oxidase in SK Hep-1 cells.

Baccharis trimera, popularly known as ??carqueja??, is a native South-American plant possessing a high concentration of polyphenolic compounds and therefore high antioxidant potential. Despite the antioxidant potential described for B. trimera, there are no reports concerning the signaling pathways involved in this process. So, the aim of the present study was to assess the influence of B. trimera on the modulation of PKC signaling pathway and to characterize the effect of the nicotinamide adenine dinucleotide phosphate oxidase enzyme (NOX) on the generation of reactive oxygen species in SK Hep-1 cells. SK-Hep 1 cells were treated with B. trimera, quercetin, or rutin and then stimulated or notwith PMA/ionomycin and labeled with carboxy H2DCFDA for detection of reactive oxygen species by flow cytometer. The PKC expression by Western blot and enzyme activity was performed to evaluate the influence of B. trimera and quercetin on PKC signaling pathway. p47phox and p47phox phosphorylated expression was performed byWestern blot to evaluate the influence of B. trimera on p47phox phosphorylation. The results showed that cells stimulated with PMA/ionomycin (activators of PKC) showed significantly increased reactive oxygen species production, and this production returned to baseline levels after treatment with DPI (NOX inhibitor). Both B. trimera and quercetin modulated reactive oxygen species production through the inhibition of PKC protein expression and enzymatic activity, also with inhibition of p47phox phosphorylation. Taken together, these results suggest that B. trimera has a potentialmechanism for inhibiting reactive oxygen species production through the PKC signaling pathway and inhibition subunit p47phox phosphorylation of nicotinamide adenine dinucleotide phosphate oxidase