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1.
Molecules ; 28(2)2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36677949

ABSTRACT

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.


Subject(s)
Antineoplastic Agents , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid , Humans , Apoptosis , Oxidative Stress , Antineoplastic Agents/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Cell Proliferation , Cellular Senescence , Pyridines/pharmacology , K562 Cells
2.
J Ethnopharmacol ; 303: 116019, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36493996

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The infusion of Serjania erecta Radlk (Sapindaceae) (popular name "cipó-cinco-folhas") leaves is used in popular medicine to treat back pain. The anti-inflammatory, anti-hyperalgesic and anti-nociceptive properties of the ethanolic extract from S. erecta leaves (EESE) has not been yet completely clarified. AIM OF THE STUDY: The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice. MATERIAL AND METHODS: EESE was fractionated by chromatographic techniques and the compound was identified by nuclear magnetic resonance (NMR), infrared (IR) spectrum, ultraviolet (UV) methods. Mice received a single dose of EESE by oral route (30, 100, and 300 mg/kg, p.o.) and were submitted to nociception induced by formalin, pleurisy induced by carrageenan and peritonitis induced by zymosan models. Mice also received EESE (30 and 100 mg/kg, p.o.) for 22 days in Complete Freund Adjuvant (CFA) model and another group received EESE for 7 days (30 and 100 mg/kg, p.o.) in pleurisy induced by Bacillus Calmette-Guerin (BCG). The cytotoxicity (MTT), phagocytic and chemotactic inhibitory activities of EESE were performed in in vitro assays. RESULTS: The fractionation of EESE led to the identification of kaempferol-3-O-α-L-rhamnopyranoside. The oral administration of all doses of EESE decreased the nociceptive response induced by formalin. EESE significantly inhibited leukocyte migration in carrageenan-induced pleurisy and zymosan peritonitis models. The daily administration of EESE during for 7 days inhibited the leukocyte migration and the mycobacteria growth of pleural material obtained from animals which received BCG. EESE significantly reduced edema, cold allodynia and mechanical hyperalgesia responses induced by CFA. EESE did not induce cytotoxicity, and also decreased the leukocyte phagocytic activity, as well as, neutrophil chemotaxis. CONCLUSIONS: EESE showed analgesic and anti-inflammatory properties in acute and persistent experimental models in mice. EESE also reduced in vitro leukocyte chemotaxis and phagocytic activity without inducing cytotoxicity. The continuous oral treatment with EESE was effective against hyperalgesia and inflammation and these results could explain the popular use of S. erecta as an analgesic natural agent.


Subject(s)
Analgesics , Anti-Inflammatory Agents , Plant Extracts , Animals , Mice , Analgesics/chemistry , Analgesics/pharmacology , Analgesics/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/chemistry , BCG Vaccine , Carrageenan , Disease Models, Animal , Edema/chemically induced , Edema/drug therapy , Edema/pathology , Ethanol , Formaldehyde , Hyperalgesia/drug therapy , Peritonitis/chemically induced , Peritonitis/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Pleurisy/chemically induced , Pleurisy/drug therapy , Sapindaceae/chemistry , Zymosan
3.
Pharmaceutics ; 14(11)2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36432646

ABSTRACT

Nonclinical trials are important to validate the efficacy and safety of medicinal plants. Scientific toxicological studies with Piper vicosanum Yuncker have showed its safety; however, no studies have indicated the analgesic or antiarthritic potential of the ethanolic extract of P. vicosanum leaves (EEPV). The objective of the present work was to evaluate the antiarthritic and antinociceptive effects of EEPV in experimental mouse models. The oral administration of EEPV (100, 300, and 700 mg/kg) and dexamethasone (1 mg/kg) were performed in carrageenan-induced pleurisy, in formalin and acetic-acid-induced nociception, and in zymosan-induced articular inflammation models in Swiss mice. The EEPV (300 mg/kg) was tested in zymosan-articular inflammation, the complete Freund's adjuvant (CFA) inflammatory model, and in in situ intravitreal microscopy analysis of rolling and adhesion events of leukocytes in the mesenteric microcirculation in mice. EEPV significantly inhibited: (i) nociceptive response at phase 1 and 2, and also in the cold response in the formalin model; (ii) abdominal contortion induced by acetic acid; (iii) mechanical hyperalgesia after 4 and 6 h, knee edema after 6 h, and leukocyte migration in articular inflammation induced by zymosan. All doses of EEPV reduced the leukocyte migration to the inflamed pleural cavity and knee edema 4 h after the zymosan knee injection. The treatment with the EEPV significantly inhibited the CFA-induced edema, mechanical and cold hyperalgesia, and NAG and MPO. The EEPV also significantly inhibited carrageenan-induced leukocyte rolling and adhesion. The present study revealed, for the first time, the antiarthritic and antinociceptive effects of the EEPV.

4.
Pharmaceuticals (Basel) ; 15(10)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36297370

ABSTRACT

The aim of this study is to evaluate the efficacy of Baccharis trimera infusion on high-fat diet-induced metabolic disorders in mice and macrophages activation. This study evaluated obesity, insulin resistance, dyslipidemia and hepatic steatosis induced by a high-fat diet in Swiss mice. Cellular parameters in macrophages, such as cell viability (MTT), the production and release of nitric oxide (NO) and hydrogen peroxide (H2O2), cell spreading, cell adhesion and phagocytosis were determined. Our results showed that treatment with B. trimera prevented the mentioned conditions, except for the production of hydrogen peroxide. B. trimera prevented the development of obesity and associated comorbidities, as well as activation of macrophages. In conclusion, B. trimera is able to prevent obesity and metabolic disorders and macrophages activation, minimizing inflammation and validating the popular use of this plant tea.

5.
Avicenna J Phytomed ; 12(4): 388-400, 2022.
Article in English | MEDLINE | ID: mdl-35782770

ABSTRACT

Objective: In the present study, the hepatoprotective effects of ß-myrcene (MYR) on acetaminophen-induced hepatotoxicity were investigated. Materials and Methods: A total of 40 Balb/c mice were randomly divided into five groups as follows: 1) Normal control group which received only carboxymethylcellulose (CMC), the vehicle used to dissolve acetaminophen (N-acetyl-p-aminophenol, APAP, paracetamol) and MYR; 2) APAP group which received a single dose of acetaminophen (250 mg/kg) orally on day 7; 3) Silymarin group which received 200 mg/kg/day of silymarin; and 4 and 5) pretreatment groups in which, mice were treated with 100 or 200 mg/kg/day of MYR. Liver and blood samples were collected to analyze serum aminotransferases, inflammatory response, oxidative stress markers, and histopathological insults. Results: Our results showed that MYR pretreatment attenuated liver damage and restored liver cells function and integrity as it decreased the leakage of serum aminotransferases (alanine and aspartate aminotransferases (ALT and AST, respectively)) into the blood (p<0.01). MYR treatment also reduced levels of myeloperoxidase (MPO) activity and nitric oxide (NO) (p<0.001). In addition, MYR pretreatment demonstrated significant antioxidant activity by decreasing malondialdehyde (MDA), reactive oxygen species (ROS), and reduced glutathione (GSH) levels (p<0.001). Furthermore, it restored the hepatic level of superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG) (p<0.001). Conclusion: For the first time, our results showed that MYR treatment significantly improved liver function by reducing oxidative stress and the inflammatory response induced by APAP.

6.
Molecules ; 27(12)2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35744789

ABSTRACT

The aim of this study is to evaluate the phytochemical profile, oral acute toxicity, and the effect of ylang-ylang (Cananga odorata Hook. F. & Thomson) essential oil (YEO) on acute inflammation. YEO was analyzed by gas chromatography/mass spectrometry. For in vitro tests, YEO was assessed using cytotoxicity, neutrophil chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP), and phagocytic activity tests. YEO was orally administered in zymosan-induced peritonitis, carrageenan-induced leukocyte rolling, and adhesion events in the in situ microcirculation model and in carrageenan-induced paw edema models. YEO (2000 mg/kg) was also tested using an acute toxicity test in Swiss mice. YEO showed a predominance of benzyl acetate, linalool, benzyl benzoate, and methyl benzoate. YEO did not present in vitro cytotoxicity. YEO reduced the in vitro neutrophil chemotaxis induced by fMLP and reduced the phagocytic activity. The oral treatment with YEO reduced the leukocyte recruitment and nitric oxide production in the zymosan-induced peritonitis model, reduced rolling and adherent leukocyte number induced by carrageenan in the in situ microcirculation model, and reduced carrageenan-induced edema and mechanical hyperalgesia. YEO did not present signs of toxicity in the acute toxicity test. In conclusion, YEO affected the leukocyte activation, and presented antiedematogenic, anti-hyperalgesic, and anti-inflammatory properties.


Subject(s)
Cananga , Oils, Volatile , Peritonitis , Animals , Cananga/chemistry , Carrageenan , Edema/chemically induced , Edema/drug therapy , Inflammation/chemically induced , Inflammation/drug therapy , Mice , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Peritonitis/chemically induced , Peritonitis/drug therapy , Zymosan
7.
Drug Chem Toxicol ; 45(6): 2699-2705, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34666582

ABSTRACT

Doliocarpus dentatus (Dilleniaceae) has been used in folk medicine to treat inflammation and pain; however, studies evaluating its toxicity potential, as well as its effects on anxiety and depression, are scarce. This study investigated the toxicological profile of an ethanolic extract from leaves of D. dentatus (EEDd), and its effects on anxiety and depression models in mice. Male and female mice received either a single dose (500, 1000 or 2000 mg/kg) or repeated doses (75, 150 or 300 mg/kg) of EEDd by oral gavage. During the subacute toxicity assay, behavioral tests were performed on days 4, 14, 21 and 28. No evidence of toxicity was observed in the animals in both acute and subacute tests. However, males treated with the highest dose presented a reduction in the absolute weight of the kidney, an elevation in the AST levels, in addition to an alteration in the urea levels. The treatment did not affect other biochemical parameters, and did not induce any depressive-like behavior. EEDd exhibited low toxicity after single and repeated exposures. Since some analyzed parameters were compromised, further toxicity studies should be carried out.


Subject(s)
Dilleniaceae , Female , Male , Mice , Animals , Plant Extracts/pharmacology , Toxicity Tests, Acute , Plant Leaves , Ethanol/toxicity , Urea
8.
J Ethnopharmacol ; 278: 114308, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34102271

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian traditional folk medicine, the leaves and heartwood from Vatairea macrocarpa (Benth) Ducke (Angelim-of-Cerrado) (Fabaceae family) are used as remedy after cold maceration for the treatment of the condition popularly known as rheumatism, as well as for the general inflammatory aspects such as pains, injury and swelling. The rheumatological and rheumatic diseases affect 0.3-1.0% of the world population and all long-term treatment with conventional medications lead to adverse effects. AIM OF THE STUDY: To investigate the chemical composition and the anti-inflammatory properties and of the ethanolic extract from V. macrocarpa leaves (EEVM) in experimental models. MATERIAL AND METHODS: EEVM was chemically analyzed by spectrophotometry and the compounds characterization was performed by nuclear magnetic resonance and mass spectrometry. EEVM was evaluated in methylthiazolyldiphenyl-tetrazolium bromide (MTT) (3, 10, 30, and 90 µg/ml) and neutrophils phagocytic activity (1, 3, and 10 µg/ml) tests. For in vivo models, the EEVM (10, 30, 100, and 300 mg/kg) was orally administered (p.o.) for inflammatory evaluation in carrageenan-induced pleurisy in Swiss mice. The EEVM (30 and 100 mg/kg, p.o.) was tested against the Complete Freund Adjuvant (CFA)-induced paw persistent inflammation and Mycobacterium bovis (bacillus Calmette-Guerin - BCG)-induced pleurisy in C57bL6 mice. RESULTS: The chemical composition of EEVM showed 157.06 mg (GAE)/g in relation to phenolic compounds, 82.13 mg (RUE)/g in relation to flavonoids and 48.99 mg (TAE)/g in relation to tannins. The flavonoid compounds identified were catechin, epicatechin and kaempferol-3-O-a-l-rhamnopyranoside. EEVM did not present cytotoxicity in MTT assay, however EEVM reduced phagocytic neutrophils activity at all tested concentration. EEVM significantly inhibited leukocytes migration/proteins exudation in carrageenan-induced pleurisy model. The daily administration of EEVM inhibited the inflammatory parameters in BCG and CFA models. CONCLUSIONS: The present study showed anti-inflammatory features of EEVM (V. macrocarpa) as a natural agent against inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Fabaceae/chemistry , Phytotherapy , Plant Extracts/pharmacology , Plant Leaves/chemistry , Pleurisy/drug therapy , Administration, Oral , Animals , Anti-Inflammatory Agents/chemistry , BCG Vaccine/toxicity , Carrageenan/toxicity , Dexamethasone/therapeutic use , Dose-Response Relationship, Drug , Ethanol/chemistry , Female , Male , Mice , Mice, Inbred C57BL , Plant Extracts/chemistry , Pleurisy/chemically induced
9.
J Ethnopharmacol ; 269: 113697, 2021 Apr 06.
Article in English | MEDLINE | ID: mdl-33316364

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain. AIM OF STUDY: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice. MATERIAL AND METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 µg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP. CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.


Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Arthralgia/drug therapy , Camphor/pharmacology , Ocimum/chemistry , Oils, Volatile/pharmacology , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Arthralgia/chemically induced , Camphor/isolation & purification , Camphor/therapeutic use , Carrageenan/toxicity , Disease Models, Animal , Edema/chemically induced , Edema/drug therapy , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Inflammation/chemically induced , Inflammation/drug therapy , Joints/drug effects , Knee Injuries/chemically induced , Knee Injuries/drug therapy , Leukocyte Rolling/drug effects , Leukocytes/drug effects , Male , Mice , Neutrophils/drug effects , Nitric Oxide/metabolism , Oils, Volatile/isolation & purification , Oils, Volatile/therapeutic use , Plant Leaves/chemistry , Synovial Fluid/drug effects , Zymosan/toxicity
10.
Article in English | MEDLINE | ID: mdl-33014104

ABSTRACT

Gomphrena celosioides Mart. (Amaranthaceae) is used in folk medicine as a natural analgesic, and in Brazil, the species of genus Gomphrena is used for rheumatism. However, scientific evidence which supports its popular use as an analgesic is scarce. This study assessed the antiarthritic and antihyperalgesic activities of the ethanolic extract obtained from G. celosioides aerial parts on Swiss or C57BL/6 mice. The antiarthritic and antihyperalgesic potential of Gomphrena celosioides was evaluated using paw edema, mechanical hyperalgesia, cold allodynia, carrageenan-induced pleurisy, articular inflammation zymosan-induced, Freund's complete adjuvant-induced inflammation zymosan-induced peritonitis, and carrageenan-induced adhesion and rolling experiment models. All doses of G. celosioides (300, 700, and 1000 mg/kg) significantly reduced edema formation in all the intervals evaluated, whereas the mechanical hyperalgesia was reduced 3 hours after the carrageenan injection. The cold hyperalgesia was significantly decreased 3 (700 mg/kg) and 4 hours (700 and 1000 mg/kg) after the carrageenan injection. Ethanolic extract of G. celosioides at 1000 mg/kg reduced the total leukocyte number, without interfering in the protein extravasation in carrageenan-induced pleurisy model. Ethanolic extract of G. celosioides (300 mg/kg) was also able to reduce significantly the leukocyte migration in zymosan-induced articular edema, while a reduction of the adhesion and migration and leukocyte rolling was induced by the ethanolic extract of G. celosioides (300 mg/kg) in zymosan-induced peritonitis. In Freund's complete adjuvant-induced inflammation model, an edema formation and mechanical hyperalgesia reduction were induced by the ethanolic extract of G. celosioides on day 22, whereas the cold allodynia was reduced on day 6 of treatment with the extract. These results show that ethanolic extract of G. celosioides has antihyperalgesic and antiarthritic potential in different acute and persistent models, explaining, at least in part, the ethnopharmacological relevance of this plant as a natural analgesic agent.

11.
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
12.
J Ethnopharmacol ; 249: 112418, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-31770567

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Eriobotrya japonica (EJ) is a Chinese medicinal plant that is currently grown in Brazil. E. japonica leaves infusion is traditionally used in the treatment of inflammation; however, there are few scientific studies showing the effects of these properties on joint articular and persistent experimental inflammation. AIM OF THE STUDY: The present research had objective investigation of the effect of infusion obtained from leaves of E. japonica (EJLE) on acute and persistent experimental articular inflammation. MATERIALS AND METHODS: The Swiss mice were treated orally with EJLE and analyzed for acute pleural inflammation (30, 100, and 300 mg/kg), paw edema induced by carrageenan (100 mg/kg), acute knee inflammation induced by zymosan (100 mg/kg), and persistent inflammation induced by Complete Freund's Adjuvant (CFA) (30 and 100 mg/kg). Mechanical hyperalgesia, cold and edema were analyzed. RESULTS: The chromatographic analysis of EJLE revealed the presence of corosolic acid, oleanolic acid, and ursolic acid. EJLE presented anti-inflammatory activity in the pleurisy model, inhibiting leukocyte migration, protein extravasation and nitric oxide production. In the articular inflammation model, EJLE reduced the number of leukocytes in the joint cavity, paw edema and hyperalgesia (4 h after induction). In the persistent inflammation model induced by CFA, the extract reduced paw edema after 11 days of mechanical and cold hyperalgesia on day 6. CONCLUSIONS: The EJLE has anti-inflammatory and antihyperalgesic potential in models of acute and persistent experimental articular inflammation, making this infusion a new possibility for complementary treating acute or chronic articular inflammatory diseases.


Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Arthralgia/drug therapy , Arthritis, Experimental/drug therapy , Eriobotrya/chemistry , Plant Extracts/pharmacology , Administration, Oral , Analgesics/isolation & purification , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/therapeutic use , Arthralgia/etiology , Arthritis, Experimental/complications , Arthritis, Experimental/immunology , Brazil , Carrageenan/administration & dosage , Carrageenan/immunology , Female , Freund's Adjuvant/administration & dosage , Freund's Adjuvant/immunology , Humans , Male , Mice , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Rats , Zymosan/administration & dosage , Zymosan/immunology
13.
Article in English | MEDLINE | ID: mdl-29743918

ABSTRACT

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 µg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine.

14.
PLoS One ; 13(1): e0190155, 2018.
Article in English | MEDLINE | ID: mdl-29324806

ABSTRACT

Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis, common zoonosis among vertebrates and high incidence worldwide. During the infection, the parasite needs to transpose the intestinal barrier to spread throughout the body, which may be a trigger for an inflammatory reaction. This work evaluated the inflammatory alterations of early T. gondii infection in peripheral blood cells, in the mesenteric microcirculation, and small intestinal tissue by measurement of MPO (myeloperoxidase) activity and NO (nitric oxide) level in rats. Animals were randomly assigned into control group (CG) that received saline orally and groups infected with 5,000 oocysts for 6 (G6), 12 (G12), 24 (G24), 48 (G48) and 72 hours (G72). Blood samples were collected for total and differential leukocyte count. Intravital microscopy was performed in the mesentery to evaluate rolling and adhesion of leukocytes. After euthanasia, 0.5cm of the duodenum, jejunum and ileum were collected for the determination of MPO activity, NO level and PCR to identify the parasite DNA and also the mesentery were collected to perform immunohistochemistry on frozen sections to quantify adhesion molecules ICAM-1, PECAM-1 and P-Selectin. The parasite DNA was identified in all infected groups and there was an increase in leukocytes in the peripheral blood and in expression of ICAM-1 and PECAM-1 in G6 and G12, however, the expression of P-selectin was reduced in G12. Leukocytes are in rolling process during the first 12 hours and they are adhered at 24 hours post-infection. The activity of MPO increased in the duodenum at 12 hours, and NO increased in the jejunum in G72 and ileum in G24, G48 and G72. Our study demonstrated that T. gondii initiates the infection precociously (at 6 hours) leading to a systemic activation of innate immune response resulting in mild inflammation in a less susceptible experimental model.


Subject(s)
Immunocompetence , Inflammation/pathology , Intestines/pathology , Toxoplasma/pathogenicity , Toxoplasmosis, Animal/pathology , Acute Disease , Animals , Intercellular Adhesion Molecule-1/metabolism , Nitric Oxide/metabolism , Peroxidase/metabolism , Rats , Real-Time Polymerase Chain Reaction , Toxoplasma/genetics , Toxoplasma/isolation & purification
15.
Article in English | MEDLINE | ID: mdl-28717379

ABSTRACT

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

16.
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
17.
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
18.
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.

19.
Am J Chin Med ; 41(4): 913-26, 2013.
Article in English | MEDLINE | ID: mdl-23895160

ABSTRACT

Essential oils are potential sources of novel components for medicinal use. The present study was performed to investigate the composition and anti-inflammatory activity of Ocimum americanum L. essential oil (OEO) and its components in an experimental model of zymosan-induced arthritis and paw edema. The essential oil was obtained by hydro-distillation and analyzed by gas chromatography-mass spectrometry. Twenty-six components, representing 98.9% of the total oil, were characterized, with linalool (19.63%) and 1,8-cineole (17.27%) as the main components. The OEO and its two constituents inhibited leukocyte influx into the synovial space and reduced paw edema induced by zymosan. The OEO also inhibited interferon-γ levels but did not reduce transforming growth factor-ß levels. Additionally, the OEO protected against leukocyte influx into the synovial membrane and cartilage destruction in knee joints in arthritic mice. These findings indicate that the essential oil of Ocimum americanum L. exerted significant anti-inflammatory effects, likely related to its main compounds.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/metabolism , Cell Movement/drug effects , Leukocytes/drug effects , Ocimum/chemistry , Oils, Volatile/pharmacology , Acyclic Monoterpenes , Animals , Arthritis, Experimental/chemically induced , Cell Migration Assays, Leukocyte , Cyclohexanols/pharmacology , Eucalyptol , Interferon-gamma/drug effects , Interferon-gamma/metabolism , Mice , Monoterpenes/pharmacology , Oils, Volatile/chemistry , Transforming Growth Factor beta/drug effects , Transforming Growth Factor beta/metabolism , Zymosan/toxicity
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