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1.
Inflammation ; 43(1): 193-203, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31631236

ABSTRACT

(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 µg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 µg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/prevention & control , Monocyclic Sesquiterpenes/pharmacology , Neutrophils/drug effects , Phagocytosis/drug effects , Sepsis/drug therapy , Animals , Bacterial Load , Cells, Cultured , Chemotaxis, Leukocyte/drug effects , Disease Models, Animal , Female , Host-Pathogen Interactions , Inflammation/immunology , Inflammation/metabolism , Inflammation/microbiology , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/microbiology , Mice, Inbred C57BL , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/microbiology , Nitric Oxide/metabolism , Peritoneum/drug effects , Peritoneum/immunology , Peritoneum/metabolism , Peritoneum/microbiology , Sepsis/immunology , Sepsis/metabolism , Sepsis/microbiology
2.
Am J Chin Med ; 45(3): 515-532, 2017.
Article in English | MEDLINE | ID: mdl-28359199

ABSTRACT

To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.


Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Antipyretics/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Cymbopogon/chemistry , Oils, Volatile/therapeutic use , Phytotherapy , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Disease Models, Animal , Male , Mice , Oils, Volatile/administration & dosage , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology
3.
Biomed Pharmacother ; 84: 1697-1704, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27847207

ABSTRACT

PURPOSE: The aim of this study was to evaluate the effect of Pogostemon cablin essential oil (PEO) on leukocyte behavior in the inflammatory response. METHODS AND RESULTS: PEO was analyzed using Gas Chromatography/Mass Spectrometry (GC/SM) and Nuclear Magnetic Resonance Spectroscopy (NMR) methods and showed predominance of patchoulol (38.50%), α-bulnesene (20.37%), α-guaiene (12.31%), seychellene (8.33%) and α-patchoulene (4.91%). PEO at concentrations of 1, 3, 10, 30, 60 and 90µg/ml reduced the in vitro neutrophil chemotaxis toward fMLP, and at concentrations of 3 and 10µg/ml, increased the phagocytic activity of neutrophils. Topical application of PEO in high concentrations promoted an increase of ear edema and myeloperoxidase (MPO) activity. However, the oral treatment with 100, 200 and 300mg/kg reduced leukocyte recruitment, nitric oxide (NO) production, and rolling and adherent leukocyte number in the microcirculation. CONCLUSION: PEO affects the leukocyte behavior, and the mechanism proposed of PEO seems to be, at least in part, involving the participation of NO and pro-inflammatory cytokines.


Subject(s)
Inflammation/pathology , Leukocytes/cytology , Sesquiterpenes/pharmacology , Acute Disease , Administration, Topical , Animals , Cell Adhesion/drug effects , Cell Survival/drug effects , Chemotaxis/drug effects , Edema/pathology , Exudates and Transudates , Gas Chromatography-Mass Spectrometry , Leukocyte Count , Leukocyte Rolling/drug effects , Leukocytes/drug effects , Male , Mice , Nitric Oxide/metabolism , Peritonitis/pathology , Peroxidase/metabolism , Phagocytosis/drug effects , Pogostemon , Sesquiterpenes/administration & dosage , Zymosan
4.
Acta sci., Health sci ; 38(2): [159-163], jul.-dez. 2016. ilus, tab
Article in English | LILACS | ID: biblio-2778

ABSTRACT

Genome-wide gene expression profiling of cancers has consistently identified the FOXM1 as one of the most commonly upregulated genes in cancer cells that plays an essential role in the regulation of a wide spectrum of biological processes, including inhibition of apoptosis. Since the anticancer activity of EUG reported in the literature is related to induction of apoptosis in cancer cells, we hypothesized that there is a correlation between the EUG-induced apoptosis effect and downregulation of FOXM1. A series of experiments were conducted to evaluate the effect of EUG on cellular viability of cancer cells (MTT) and its potential regulatory effect on FOXM1 protein levels (western blots). Our findings confirm the anticancer effect of EUG on different human cancer cell lines as previously reported in the literature (SKBR3 LC50: 318.6; HT29 LC50: 525.5; and HepG2 LC50: 2090.0 µM). However, we demonstrated that EUG does not regulate the FOXM1. The results evidenced the anticancer effect of EUG on three cancer cell lines and showed that the EUG- apoptosis induced effect is not related to regulation of FOXM1 at the protein level. Further studies must be done to provide information on the mechanism of action of this agent.


Estudos do genoma de células tumorais identificaram o FOXM1 como o fator de transcrição mais expresso, desempenhando papel essencial em uma gama de processos biológicos, incluindo a inibição da apoptose celular. A atividade anticarcinogênica do EUG, relatada na literatura, está relacionada à indução de apoptose em células cancerosas, por isso geramos a hipótese de que pode existir correlação entre este efeito indutor de apoptose e a supressão do FOXM1. Um conjunto de experimentos foi realizado com o objetivo de avaliar o efeito do EUG na viabilidade celular (MTT) e o potencial regulatório sobre o nível de proteínas do FOXM1, em células cancerosas (western blots). Nossos resultados corroboram o efeito anticancerígeno do EUG relatado na literatura em diferentes linhagens celulares (SKBR3 LC50: 318.6; HT29 LC50: 525.5; e HepG2 LC50: 2090.0 µM). Entretanto ficou demonstrado que o EUG não interfere no nível proteico do FOXM1. Em nosso estudo demonstramos o efeito citotóxico do EUG em três linhagens celulares de câncer, sendo evidenciado que o efeito indutor de apoptose promovido pelo mesmo não é dependente da regulação do fator de transcrição FOXM1. Estudos mais detalhados serão conduzidos no intuito de esclarecer os mecanismos de ação desde agente anticarcinogênico.


Subject(s)
Oils, Volatile , Apoptosis , Syzygium , Cytotoxicity, Immunologic
5.
Bioorg Med Chem Lett ; 26(5): 1411-5, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26850006

ABSTRACT

Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antioxidants/pharmacology , Edema/drug therapy , Peritonitis/drug therapy , Salicylates/pharmacology , Stilbenes/pharmacology , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Carrageenan , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Hep G2 Cells , Humans , Hydrogen Peroxide/antagonists & inhibitors , Hydrogen Peroxide/pharmacology , Mice , Molecular Structure , Oxidative Stress/drug effects , Prostaglandin-Endoperoxide Synthases/metabolism , Reactive Oxygen Species/metabolism , Resveratrol , Salicylates/chemistry , Stilbenes/administration & dosage , Stilbenes/chemistry , Structure-Activity Relationship
6.
Article in English | MEDLINE | ID: mdl-25152763

ABSTRACT

Estragole, a chemical constituent of the essential oils of many aromatic plants, is used as flavoring in beverage and food industries. In vivo and in vitro experimental assays have shown that EST has sedative, anticonvulsant, antioxidant, antimicrobial, and anesthetic activity. In this work, we evaluate the effect of EST on leukocyte behavior and phagocytic activity of macrophages. In the peritonitis model, EST (500 and 750 mg/kg) decreased the infiltration of peritoneal exudate leukocytes. In vitro chemotaxis assay showed that EST (3, 10, 30, and 60 µg/mL) inhibited neutrophil migration toward fMLP. In the in vivo microcirculation assay, EST at doses of 250, 500, and 750 mg/kg significantly reduced the number of rolling and adherent leukocytes and at doses of 250 and 500 mg/kg decreased number of leukocyte migrated to perivascular tissue. The results showed that EST (3, 10, and 30 µg/mL) was able to stimulate the macrophages phagocytosis but only at concentration of 10 µg/mL promoted an increase in nitric oxide (NO) production. In conclusion, this study showed that EST had potential anti-inflammatory effects, likely by inhibiting leukocyte migration and by stimulating macrophages phagocytosis.

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