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Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine 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 imidazo[1,2-a]pyridine 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 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

Made available in DSpace on 2021-06-25T11:05:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 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. School of Health Sciences Federal University of Grande Dourados (UFGD) School of Health Sciences University Center of Grande Dourados (UNIGRAN) Dourados College of Pharmaceutical Sciences Food and Nutrition Federal University of Mato Grosso Do sul (UFMS) Research Center for Biosciences and Health Technologies (CBIOS) Lusofona University Institute of Biology Department of Plant Biology Ppg BTPB Ppg Bce University of Campinas (UNICAMP) Brazil Institute of Biology Department of Structural and Functional Biology Institute of Biosciences of Botucatu Unesp-University Estadual Paulista-Botucatu Department of Structural and Functional Biology Institute of Biosciences of Botucatu Unesp-University Estadual Paulista-Botucatu

Serjania marginata Casar (Sapindaceae Family) Leaves are popularly used against abdominal pain. Antiulcer properties of S. marginata were scientifically described, however rare studies showed the antinociceptive effects of this plant.In this study, we investigated the antinociceptive and anti-inflammatory effects of aqueous extract obtained from Serjania marginata leaves (AESM) in nociception/inflammation models.AESM was analyzed in FIA-ESI-IT-MS and Mass spectrometer LTQ XL. AESM oral administration (p.o.) (30, 100 and 300 mg/kg), dexamethasone subcutaneous injection (1 mg/kg, s.c.) and morphine (5 mg/kg, s.c.) were tested against the acetic acid-induced nociception, carrageenan-induced acute inflammatory paw edema/hyperalgesia, formalin-induced nociception and carrageenan-induced pleurisy in Swiss mice.Flavonoids rutin was detected in the phytochemical analysis of this extract. Oral treatment of AESM 300 mg/kg significantly reduced the number of acetic acid-induced abdominal writhing. AESM (100 and 300 mg/kg) significantly inhibited formalin-induced nociception, mechanical hyperalgesia and paw edema in carrageenan-model. Furthermore, AESM significantly inhibited leukocyte migration and protein exudation in the carrageenan-induced pleurisy test.This study confirms the antinociceptive, and anti-inflammatory activity of AESM, which may explain, in part, the popular use of this plant as a natural antinociceptive agent. This pharmacological action can be caused by flavonoids such as rutin and other compounds present in AESM.

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.The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice.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.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.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.

Made available in DSpace on 2022-05-01T09:47:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 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. Faculty of Health Sciences Federal University of Grande Dourados Postgraduate Program in Chemistry Faculty of Exact Sciences and Technology Federal University of Grande Dourados Faculty of Health Sciences University Center of Grande Dourados Faculty of Exact and Agrarian Sciences University Center of Grande Dourados Center of Studies in Natural Resources State University of Mato Grosso Do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP–Paulista State University Pharmaceutical Sciences Food and Nutrition College Federal University of Mato Grosso do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu UNESP–Paulista State University

Basil is an aromatic and medicinal plant that has a wide variety of species due to cross-pollination processes that influence germination and properties. In this work, germination parameters of six different basil species were evaluated in order to describe which ones have the highest germination potential. For this, the basil varieties were grown in a greenhouse at 20-25 oC, and the germination percentage was monitored for 14 days. The Weibull modeling allowed us to evaluate that the species O. basilicum var. basilicum, O. Basilicum var. purpurascens and O. basilicum minimum are those that germinate in large proportions and that O. basilicum L. cv. Genovese has an intense dormancy process. Considering the germination time, the species O. basilicum var. basilicum is the variety with the highest germination potential. La albahaca es una planta aromática y medicinal que presenta una gran variedad de especies debido a procesos de polinización cruzada que influyen en la germinación y propiedades. En este trabajo se evaluaron los parámetros de germinación de seis especies diferentes de albahaca con el fin de describir cuáles tienen el mayor potencial de germinación. Para ello, las variedades de albahaca se cultivaron en invernadero a 20-25 oC, y se monitoreó el porcentaje de germinación durante 14 días. El modelado de Weibull nos permitió evaluar que la especie O. basilicum var. basilicum, O. Basilicum var. purpurascens y O. basilicum minimum son las que germinan en mayor proporción y que O. basilicum L. cv. Genovese tiene un intenso proceso de latencia. Considerando el tiempo de germinación, la especie O. basilicum var. basilicum es la variedad con mayor potencial de germinación. O manjericão é uma planta aromática e medicinal que apresenta grande variedade de espécies devido a processos de polinização cruzada e que influenciam a germinação e propriedades. Neste trabalho, foram avaliados parâmetros de germinação de seis espécies diferentes de manjericão visando descrever quais apresentam maior potencialidade de germinação. Para isso, as variedades de manjericão foram cultivadas em estufa entre 20-25 oC, e a porcentagem de germinação monitorada por 14 dias. A modelagem de Weibull permitiu avaliar que as espécies O. basilicum var. basilicum, O. Basilicum var. purpurascens and O. basilicum minimum são aquelas que germinam em grande proporção e que a O. basilicum L. cv. Genovese apresenta intenso processo de dormência. Considerando o tempo de germinação, a espécie O. basilicum var. basilicum é a varidade com maior potencial de germinação

(-)-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.

In the present study, the hepatoprotective effects of β-myrcene (MYR) on acetaminophen-induced hepatotoxicity were investigated.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.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 (p0.01). MYR treatment also reduced levels of myeloperoxidase (MPO) activity and nitric oxide (NO) (p0.001). In addition, MYR pretreatment demonstrated significant antioxidant activity by decreasing malondialdehyde (MDA), reactive oxygen species (ROS), and reduced glutathione (GSH) levels (p0.001). Furthermore, it restored the hepatic level of superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG) (p0.001).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.

Made available in DSpace on 2021-06-25T11:18:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-05 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Federal University of Grande Dourados Faculty of Health Sciences Pharmaceutical Sciences Food and Nutrition College Federal University of Mato Grosso Do Sul, Mato Grosso do Sul State Department of Structural and Functional Biology Institute of Biosciences of Botucatu Universidade Estadual Paulista (UNESP) - Botucatu, São Paulo State School of Health Sciences University Center of Grande Dourados (UNIGRAN) Center of Studies in Natural Resources State University of Mato Grosso Do Sul (UEMS) School of Medicine Federal University of Mato Grosso Do Sul Department of Epidemiology of Microbial Diseases Yale University School of Public Health Oswaldo Cruz Foundation Department of Structural and Functional Biology Institute of Biosciences of Botucatu Universidade Estadual Paulista (UNESP) - Botucatu, São Paulo State

Serotonin (5-HT) receptors are found throughout central and peripheral nervous systems, mainly in brain regions involved in the neurobiology of anxiety and depression. 5-HT receptors are currently promising targets for discovering new drugs for treating disorders ranging from migraine to neuropsychiatric upsets, such as anxiety and depression. It is well described in the current literature that the brain expresses seven types of 5-HT receptors comprising eighteen distinct subtypes. In this article, we comprehensively reviewed 5-HT1-7 receptors. Of the eighteen 5-HT receptors known today, thirteen are G protein-coupled receptors (GPCRs) and represent targets for approximately 40% of drugs used in humans. Signaling pathways related to these receptors play a crucial role in neurodevelopment and can be modulated to develop effective therapies to treat anxiety and depression. This review presents the experimental evidence of the modulation of the “serotonergic receptosome” in the treatment of anxiety and depression, as well as demonstrating state-of-the-art research related to phytochemicals and these disorders. In addition, detailed aspects of the pharmacological mechanism of action of all currently known 5-HT receptor families were reviewed. From this review, it will be possible to direct the rational design of drugs towards new therapies that involve signaling via 5-HT receptors.

Pterodon pubescens, popularly known as "sucupira", it is traditionally used as anti-inflammatory agent. This work aimed to evaluate the in vivo antiarthritic properties of a P. pubescens oil nanoemulsion and the rheological behavior of the developed system. The viscoelastic properties, creep and recovery were evaluated by dynamic oscillatory tests. The antiarthritic activity of the nanoemulsion was evaluated by the zymozan-induced arthritis model, at three different doses (25, 50 and 125 mg/kg/day). P. pubescens oil nanoemulsion has been shown to decrease cell recruitment to a joint cavity and increased cartilaginous regeneration at the end of treatment of the dose of 50 mg/kg. The evaluation of the behaviour of deformation allowed to observe that the P. pubescens nanoemulsion presents predominantly elastic characteristic. These findings demonstrate the potential of P. pubescens and nanotechnology in the development of new antiarthritic drugs. Pterodon pubescens, conocido popularmente como "sucupira", se usa tradicionalmente como antiinflamatorio. Este trabajo tuvo como objetivo evaluar las propiedades antiartríticas in vivo de una nanoemulsión que contiene lo aceite de P. pubescens y el comportamiento reológico del sistema desarrollado. Las propiedades viscoelásticas, fluencia y recuperación se evaluaron mediante ensayos oscilatorios dinámicos. La actividad antiartrítica de la nanoemulsión se evaluó mediante el modelo de artritis inducida por zimozan, en tres concentraciones diferentes (25, 50 y 125 mg/kg/día). Se ha demostrado que la nanoemulsión que contiene aceite de P. pubescens en la dosis de 50 mg/kg disminuye el reclutamiento de células a la cavidad articular y aumenta la regeneración del cartílago al final del tratamiento. La evaluación del comportamiento de deformación permitió observar que la nanoemulsión de P. pubescens tiene una característica predominantemente elástica. Estos hallazgos demuestran el potencial del uso de P. pubescens en nanotecnología para el desarrollo de nuevos fármacos antiartríticos. Pterodon pubescens, popularmente conhecido como "sucupira", é tradicionalmente utilizado como anti-inflamatório. Este trabalho teve o objetivo de avaliar as propriedades antiartríticas in vivo de uma nanoemulsão contendo o óleo de P. pubescens e o comportamento reológico do sistema desenvolvido. As propriedades viscoelásticas, fluência e recuperação foram avaliadas por testes oscilatórios dinâmicos. A atividade antiartrítica da nanoemulsão foi avaliada pelo modelo de artrite induzida por zimozan, em três diferentes concentrações (25, 50 e 125 mg/kg/dia). Demonstrou-se que a nanoemulsão contendo o óleo de P. pubescens na dose de 50 mg/kg diminui o recrutamento de células para uma cavidade articular e aumenta a regeneração cartilaginosa no final do tratamento. A avaliação do comportamento de deformação permitiu observar que a nanoemulsão de P. pubescens apresenta característica predominantemente elástica. Esses achados demonstram o potencial da aplicação de P. pubescens na nanotecnologia para o desenvolvimento de novos medicamentos antiartríticos.

In the state of Mato Grosso do Sul, Brazil, Piper glabratum leaves are used as a popular medicine for pain and inflammation. We performed a phytochemical analysis and evaluated the effects of ethanolic extract (EEPG) obtained from leaves of P. glabratum on toxicity as well as the effects of application of the hexanic fraction (HXPG) and the hydroalcoholic fraction (HAPG) obtained from the EEPG on inflammatory parameters and pain in mice. Swiss mice were treated with EEPG (30–300 mg/kg body weight (b.w.)), HXPG (19.5 mg/kg b.w.) or HAPG (83.37 mg/kg b.w.) and then subjected to carrageenan-induced pleurisy and paw oedema tests, the spontaneous pain, and zymosan-induced intra-articular inflammation. Wistar rats were treated with EEPG to assess acute toxicity. Phytochemical analysis of the fractions demonstrated the presence of phytol and mixture of stigmasterol and β-sitosterol in the fractions. In the acute toxicity test, LD50 above 2000 mg/kg b.w. was observed. The treatments reduced oedema, cold and mechanical hyperalgesia, leukocyte migration and protein exudation. The antihyperalgesic and anti-inflammatory properties of EEPG and fractions were demonstrated in the present study. These results from EEPG and HXPG may be related, at least in part, to modulation of the inflammatory mediators by phytol, stigmasterol and β-sitosterol.

Lavandula angustifoliais 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 ofLavandula angustifoliaMill. 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 presentin vitrocytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxisin 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.

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.

The natural products extracted from plants are part of traditional medicine and are also therapeutic possibilities for treating many diseases. Recently, its use in the development of new drugs has shown much visibility for its efficiency and few adverse effects. Essential oils extracted from medicinal plants are indicated to treat numerous diseases due to their antimicrobial, antiviral, antimutagenic, anticancer, antioxidant, anti-inflammatory, immunomodulatory, and antiprotozoal properties. Among essential oils, lavender essential oil stands out for having several important pharmacological properties. This review detailed the main studies on essential oils from different species of lavender and obtained a valuable collection on all their pharmacological, medicinal and toxicological potential. In this context, we evaluated lavender essential oil as a promising substance that can help treat several diseases. We provide some evidence and an overview of the potential therapeutic effect of lavender essential oil to guide new research. Los productos naturales extraídos de las plantas forman parte de la medicina tradicional y también son posibilidades terapéuticas para el tratamiento de muchas enfermedades. Recientemente, su uso en el desarrollo de nuevos fármacos ha mostrado mucha visibilidad por su eficacia y pocos efectos adversos. Los aceites esenciales extraídos de plantas medicinales están indicados para tratar numerosas enfermedades por sus propiedades antimicrobianas, antivirales, antimutagénicas, anticancerígenas, antioxidantes, antiinflamatorias, inmunomoduladoras y antiprotozoarias. Entre los aceites esenciales, el aceite esencial de lavanda se destaca por tener varias propiedades farmacológicas importantes. Esta revisión detalló los principales estudios sobre aceites esenciales de diferentes especies de lavanda y obtuvo una valiosa colección sobre todo su potencial farmacológico. En este contexto, evaluamos el aceite esencial de lavanda como una sustancia prometedora que puede ayudar a tratar varias enfermedades. Proporcionamos algunas pruebas y una descripción general del posible efecto terapéutico del aceite esencial de lavanda para guiar nuevas investigaciones. In Os produtos naturais extraídos das plantas fazem parte da medicina tradicional e também são possibilidades terapêuticas para o tratamento de muitas doenças. Recentemente, seu uso no desenvolvimento de novos medicamentos tem mostrado muita visibilidade por sua eficácia e poucos efeitos adversos. Os óleos essenciais extraídos de plantas medicinais são indicados para o tratamento de inúmeras doenças devido às suas propriedades antimicrobiana, antiviral, antimutagênica, anticâncer, antioxidante, antiinflamatória, imunomoduladora e antiprotozoária. Dentre os óleos essenciais, o óleo essencial de lavanda se destaca por possuir diversas propriedades farmacológicas importantes. Esta revisão detalhou os principais estudos sobre os óleos essenciais de diferentes espécies de lavanda e obteve um valioso acervo sobre todo o seu potencial farmacológico, medicinal e toxológico. Nesse contexto, avaliamos o óleo essencial de lavanda como uma substância promissora que pode auxiliar no tratamento de diversas doenças. Fornecemos algumas evidências e uma visão geral do potencial efeito terapêutico do óleo essencial de lavanda para orientar novas pesquisas.

Made available in DSpace on 2021-06-25T11:09:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-06 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul 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. School of Health Sciences Federal University of Grande Dourados School of Health Sciences University Center of Grande Dourados (UNIGRAN) Pharmaceutical Sciences Food and Nutrition College Federal University of Mato Grosso do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu Universidade Estadual Paulista (UNESP) Department of Pharmacology and Therapeutics State University of Maringá (UEM) School of Medicine Federal University of Mato Grosso do Sul Department of Structural and Functional Biology Institute of Biosciences of Botucatu Universidade Estadual Paulista (UNESP) Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul: 59/300.130/2016

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.

A prevalencia do diabetes vem crescendo mundialmente, configurando-se atualmente como uma epidemia resultante, em grande parte, do envelhecimento da populacao. Contudo, o sedentarismo, a alimentacao inadequada e o aumento da obesidade tambem sao responsaveis pela expansao global do diabetes. Os suplementos nutricionais ergogenicos sao aqueles que podem promover aumento do desempenho fisico alem da capacidade fisiologica, e apresentam uma acao termogenica no organismo. Entretanto, a atividade biologica e validacao cientifica destes suplementos ainda carecem de estudos para a sua comprovacao clinica quanto aos seus beneficios termogenicos, colocando assim em duvida a eficiencia dessas substâncias. O objetivo deste trabalho foi avaliar o efeito da suplementacao com dextrose, sobre os niveis glicemicos em animais diabeticos tipo 2. Para isso foi utilizado 38 ratos machos da linhagem Wistar, sendo 14 normoglicemicos e 24 diabeticos, os animais foram submetidos a gaiola metabolica afim de verificar o consumo de agua e alimento, volume de urina e glicosuria, apos isto foram tratados com dextrose, e submetidos aos testes bioquimicos. Nossos resultados indicam que a suplementacao com dextrose, uma substância ergogenica, frequentemente utilizada em atividades fisicas e exercicios nao induz um estado de hiperglicemia em animais diabeticos ou alteracao da funcao hepatica nestes animais

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.

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.

Aims: Liver diseases have become one of the major causes of morbidity and mortality all over the world. This study investigated the hepatoprotective and antioxidant effect of rosemary essential oil (REO) and ginger essential oil (GEO), against paracetamol-induced liver damage. Methodology: The hepatoprotective effects of REO and GEO at doses of 125, 250 and 500 mg/kg, respectively, orally for 7 days were determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity. In vitro antioxidant activity of REO and GEO were evaluated by assessing the free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging activity and lipid peroxidation. Results: REO and GEO reduced the levels of the serum marker enzymes AST, ALT, and MPO activity. The essentials oils also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. Conclusion: These results suggest that REO and GEO have hepatoprotective effects on acetaminophen-induced hepatic damage in mice probably due to their antioxidant effect.

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.

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-β 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.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications in inflammatory illnesses. However, the gastrointestinal bleeding and toxicity associated with NSAIDs long term use prompted the quest towards investigations for new anti-inflammatory agents. Natural and natural-derived molecules proved its anti-inflammatory efficacy in vitro as well as in vivo. Given this background, the scope of this research involves structural changes of the natural polyphenol (tyrosol) generating two new salicylate derivatives and testing their biological properties , focusing in anti-inflammatory effects assessed in vitro and in vivo assays. The first molecular modification was the introduction of a carboxylic acid group adjacent to the phenol group present in this compound, which creates a new salicylate-like tyrosol. In addition, the acetylation of phenol group in this molecule produced an acetylsalicylate derivative, which may be regarded as aspirin-like natural polyphenol. Interestingly, tyrosol and its novel derivatives attenuated the edema in acute inflammatory response on carrageenan-induced local inflammation in mice. In addition, our results demonstrated that tyrosol and its novel derivatives were able to reduce the chemotaxis of neutrophil assessed in vitro model by chemo attractant (fMLP). Furthermore, only derivative 2 was able to reduce this effect in the acute inflammatory model. In (DPPH)-scavenging activity, tyrosol derivatives demonstrated a minor antioxidant activity, which may suggest that radical scavenging is not a major pathway involved in the anti-inflammatory effects of these derivatives.. Salicylate-like tyrosol derivatives are of particular interest for future studies.

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 90 μg/ml reduced the in vitro neutrophil chemotaxis toward fMLP, and at concentrations of 3 and 10 μg/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 300 mg/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.

Estragole, a chemical constituent of the essential oils of many aromatic plants, is used as flavoring in beverage and food industries.In vivoandin vitroexperimental 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 vitrochemotaxis assay showed that EST (3, 10, 30, and 60 μg/mL) inhibited neutrophil migration toward fMLP. In thein vivomicrocirculation 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.

Ylang-ylang (Cananga odorata) is a medicinal plant of the Annonaceae family, with many therapeutic properties and biological activities, such as anxiolytic, antimicrobial, antioxidative, anti-inflammatory activities, among others. The aim of this study was to evaluate the chemical composition, oral acute toxicity, and the effect of ylang-ylang essential oil (YEO) on the acute inflammatory response in experimental models. YEO was analyzed by gas chromatography/mass spectrometry. For in vitro tests, YEO was evaluated in methylthiazolyldiphenyl-tetrazolium bromide (MTT) test, neutrophil chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP), and phagocytic activity tests. The YEO was orally administered in zymosan-induced peritonitis, carrageenan-induced leukocyte rolling and adhesion events in the in situ microcirculation model, and carrageenan-induced paw oedema models. The YEO (2000 mg/kg) was also tested in acute toxicity test in Swiss mice. YEO showed predominance of benzyl acetate, linalool, benzyl benzoate, and methyl benzoate. YEO did not present in vitro cytotoxicity. YEO at concentrations of 10, 30, 60 and 90 μg/mL reduced the in vitro neutrophil chemotaxis induced by fMLP, and at concentrations of 10, 30, and 90 μg/mL, reduced the phagocytic activity. The oral treatment with YEO at doses of 100 and 200 mg/kg reduced the leukocyte recruitment, nitric oxide (NO) production in zymosan-induced peritonitis model, reduced rolling and adherent leukocyte number induced by carrageenan in the in situ microcirculation, and reduced carrageenan-induced edema and mechanical hyperalgesia. YEO did not present signs of toxicity in acute toxicity test. In conclusion, YEO affected the leukocyte activation, presented antiedematogenic, antihyperalgesic and anti-inflammatory properties in experimental models. NO may be involved in OEY mechanism of action, but other inflammatory pathways cannot be ruled out. A Cananga odorata, popularmente conhecida como ylang-ylang, é uma planta medicinal pertencente à família Annonaceae, com diversas propriedades e atividades biológicas já descritas na literatura, tais como: ansiolítica, antimicrobiana, antioxidante, anti-inflamatória, dentre outras. O objetivo deste estudo foi determinar a composição química, a toxicidade aguda oral e o efeito do óleo essencial de ylang-ylang (OEY) sobre a resposta inflamatória aguda em modelos experimentais. Para a análise fitoquímica, o OEY foi analisado por cromatografia gasosa/espectrometria de massa. Nos ensaios in vitro, foi avaliada a citotoxicidade do OEY por meio do teste de brometo de metiltiazolildifenil-tetrazólio (MTT); o efeito do OEY na quimiotaxia de neutrófilos induzida por N-formil metionil leucil fenilalanina (fMLP); e na de atividade fagocitária de neutrófilos. O OEY foi administrado por via oral nos ensaios de peritonite induzida por zymosan, de microcirculação in situ, sobre o rolamento e adesão de leucócitos induzidos por carragenina, e nos modelos de edema de pata e de hiperalgesia induzidos por carragenina. O OEY (na dose 2000 mg/kg) também foi testado na toxicidade aguda em camundongos. O OEY apresentou predominância de acetato de benzila, linalol, benzoato de benzila e benzoato de metila, em sua constituição. Nos testes in vitro, o OEY não apresentou citotoxicidade, reduziu a quimiotaxia de neutrófilos induzida por fMLP nas concentrações de 10, 30, 60 e 90 μg/mL, e nas concentrações de 10, 30 e 90 μg/mL; reduziu a atividade fagocitária de neutrófilos. O tratamento oral com OEY nas doses de 100 e 200 mg/kg reduziu o recrutamento de leucócitos e a produção de óxido nítrico (NO) no modelo de peritonite induzida por zymosan, reduziu o rolamento e adesão de leucócitos induzidos por carragenina na microcirculação in situ e reduziu o edema e hiperalgesia mecânica induzidos por carragenina. O OEY não apresentou sinais de toxicidade no teste de toxicidade aguda. Em conclusão, o OEY reduziu a ativação leucocitária, apresentando propriedades antiedematogênicas, anti-hiperalgésicas e anti-inflamatórias em modelos experimentais. O NO pode estar envolvido no mecanismo de ação do OEY, porém as demais vias inflamatórias não podem ser descartadas.