Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae)

In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol. The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono- and sesquiterpenes and the majority compound was nerolidol. Therefore, antiulcerogenic activity of nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin- and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p < 0.05). The percentage of inhibition of ulcer was 41.22, 51.31, 56.57 and 53.50% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. Regarding ethanol- and indomethacin-induced ulcer models, it was observed that the treatment with nerolidol (250 and 500 mg/kg) significantly reduced the ULI in comparison with the control group (p < 0.05). The dose of 50 mg/kg reduced the parameters analyzed but this was not statistically significant. In the ethanol-induced model percentage of inhibition of ulcer was 34.20, 52.63, 87.63 and 50.87% in groups treated with 50, 250, 500 mg/kg of nerolidol and 30 mg/kg of omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. The results of this study show that nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of nerolidol for the treatment of gastric ulcer. © 2007 Verlag der Zeitschrift für Naturforschung.

Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis

Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. © 2008 Pharmaceutical Society of Japan.

Preemptive dexamethasone and etoricoxib for pain and discomfort prevention after periodontal surgery: A double-masked, crossover, controlled clinical trial

Background: Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. Methods: For this prospective, double-masked, crossover, placebo-controlled, randomized clinical trial, open-flap debridement surgeries were performed on 15 patients (eight males and seven females, age range 20 to 56 years: mean age ± SD: 40 ± 9.7 years) who presented with chronic periodontitis after nonsurgical periodontal therapy at three quadrants. Each patient underwent three surgical procedures at intervals of 30 days and received one of the following premedication protocols 1-hour before surgery: group 1 = placebo, group 2 = 8 mg dexamethasone, and group 3 = 120 mg etoricoxib. Rescue medication (750 mg acetaminophen) was given to each patient who was instructed to take it when necessary. Pain intensity and discomfort were evaluated by a 101-point numeric rate scale and a four-point verbal rate scale, respectively, hourly for the first 8 hours after surgery and three times a day on the following 3 days. Results: The results demonstrate that groups 2 and 3 present reduced postoperative pain-intensity levels compared to group 1. There were statistically significant differences at the 4, 5, 6, 7, and 8 hour-periods after surgery (Friedman test; P<0.05). Furthermore, rescue-medication intake was significantly lower for groups 2 and 3 than for group 1 (analysis of variance; P<0.02). Conclusion: The adoption of a preemptive medication protocol using etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

Anti-inflammatory activity of Lychnophora passerina, Asteraceae (Brazilian arnica)

Ethnopharmacological relevance: Lychnophora passerina (Asteraceae), popularly known as arnica, is used to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. Materials and methods: The anti-inflammatory activity of crude ethanolic extract of aerial parts of L. passerina and its ethyl acetate and methanolic fractions had their abilities to modulate the production of NO, TNF-α and IL-10 inflammatory mediators in LPS/IFN-γ-stimulated J774.A1 macrophages evaluated. Moreover, the crude ethanolic extract and derived fractions were also in vivo assayed by carrageenan-induced paw oedema in mice. Results: In vitro assays showed remarkable anti-inflammatory activity of L. passerina crude ethanolic extract (EE) and its ethyl acetate (A) and methanolic (M) fractions, through the inhibition of production of NO and TNF-α inflammatory mediators and induction of production of IL-10 anti-inflammatory cytokine. In vivo assays showed anti-inflammatory activity for EE 10% ointment, similar to the standard drug diclofenac gel. The A and M fraction ointments 20% presented anti-inflammatory activity. Conclusion: The results obtained showed that possible anti-inflammatory effects of EE and its A and M fractions may be attributed to inhibition pro-inflammatory cytokines production, TNF-α and NO and to increased IL-10 production. EE, A and M ointments showed topical in vivo anti-inflammatory activity. The in vivo anti-inflammatory activity of EE of L. passerina may be related to synergistic effects of different substances in the crude extract. Therefore, traditional use of aerial parts of L. passerina in the inflammatory conditions could be beneficial to treat topical inflammatory conditions, as evidenced by the present study. © 2011 Elsevier B.V. All rights reserved.

Neurocysticercosis: The enigmatic disease

Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae = CC) and racemose cysts (Cysticercus racemosus = CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed. © 2011 Bentham Science Publishers.

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model

Ethnopharmacological relevance: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. Aim of the study: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. Materials and methods: ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. Results: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. Conclusions: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. © 2013 Elsevier B.V. All rights reserved.

Expression of annexin-A1 and galectin-1 anti-inflammatory proteins and mRNA in chronic gastritis and gastric cancer

Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association with H. pylori infection. Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay. Results. High ANXA1 mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26 ± 2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38 ± 4.77). However, LGALS1 mRNA levels were high (mean RQ = 2.44 ± 3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43 ± 3.13; P < 0.01). Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins. Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis. © 2013 Yvana Cristina Jorge et al.

Anti-inflammatory and analgesic evaluation of hydroalcoholic extract and fractions from seeds of Piper cubeba L. (Piperaceae)

Some of the Piper species have been applied for the treatment of several diseases (anti-oxidant, antimicrobial, anti-inflammatory, and analgesic), considering multiple applications used in traditional medicine of different countries. About these, the present study evaluated some biological activities of Piper cubeba, as writhing test induced by acetic acid, ear edema induced by croton oil and paw edema induced by carrageenan were used by evaluated the analgesic and anti-inflammatory activities of crude hydroalcoholic extract (PCE) and its fractions of different polarities of P. cubeba L. seeds. The lethal dose (LD50) and the effective dose (ED50) were evaluated too. Both the PCE and dichloromethane fraction showed decrease values of edema and abdominal constrictions. The results obtained in this study confirm the low toxicity and analgesic and anti-inflammatory activities of PCE from P. cubeba seeds, justifying its use in folk medicine. Copyright © 2013, Phcog.Net, Published by Reed Elsevier India Pvt. Ltd. All rights reserved.

Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro

Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1-/- mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach. Copyright © 2013 by The American Association of Immunologists, Inc.

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

Ethnopharmacological relevance Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities. It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action. Thus, the goal of this study was to verify the antioxidant activity and to explore the anti-inflammatory properties of propolis by addressing its intracellular mechanism of action. Caffeic acid was investigated as a possible compound responsible for propolis action. Materials and methods The antioxidant properties of propolis and caffeic acid were evaluated by using the 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging method. To analyze the anti-inflammatory activity, Raw 264.7 macrophages were treated with different concentrations of propolis or caffeic acid, and nitric oxide (NO) production, a strong pro-inflammatory mediator, was evaluated by the Griess reaction. The concentrations of propolis and caffeic acid that inhibited NO production were evaluated on intracellular signaling pathways triggered during inflammation, namely p38 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK1/2), the transcription nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK1/2), through Western blot using specific antibodies. A possible effect of propolis on the cytotoxicity of hepatocytes was also evaluated, since this product can be used in human diets. Results Caffeic acid showed a higher antioxidant activity than propolis extract. Propolis and caffeic acid inhibited NO production in macrophages, at concentrations without cytotoxicity. Furthermore, both propolis and caffeic acid suppressed LPS-induced signaling pathways, namely p38 MAPK, JNK1/2 and NF-κB. ERK1/2 was not affected by propolis extract and caffeic acid. In addition, propolis and caffeic acid did not induce hepatotoxicity at concentrations with strong anti-inflammatory potential. Conclusions Propolis exerted an antioxidant and anti-inflammatory action and caffeic acid may be involved in its inhibitory effects on NO production and intracellular signaling cascades, suggesting its use as a natural source of safe anti-inflammatory drugs. © 2013 Elsevier B.V.

Immunomodulatory/anti-inflammatory effects of Baccharis dracunculifolia leaves

A possible immunomodulatory/anti-inflammatory effect of Baccharis dracunculifolia (Bd) and its major compound - caffeic acid (Ca) - on cytokines production (IL-1b, IL-6 and IL-10) by murine macrophages was investigated. Cells were incubated with Bd and Ca, and the inhibitory concentrations were tested before or after macrophages challenge with LPS. Bd and Ca stimulated IL-1b and inhibited IL-6 and IL-10 production. In LPS-challenge protocols, Bd prevented LPS action either before or after LPS challenge, whereas Ca prevented LPS effects only after LPS addition. Bd modulatory action on cytokines production may be at least in part mediated by Ca, since it has been shown to inhibit the transcription factor NF-kB. Further studies are still needed to evaluate Bd efficacy in inflammatory diseases, in order to explore its antiinflammatory activity in vivo. © 2013 Taylor & Francis.

Antitumour and anti-inflammatory effects of palladium(II) complexes on Ehrlich tumour

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Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor

Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. © 2013 Elsevier Inc.

Cetoprofeno e expressão de citocinas TNF-alfa e IL-1 após hemorragia aguda em ratos

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Anti-inflammatory and opioid-like activities in methanol extract of Mikania lindleyana, sucuriju

ABSTRACT: Mikania lindleyana DC., Asteraceae (sucuriju), grows in the Amazon region, where is frequently used to treat pain, inflammatory diseases and scarring. This study was carried out to investigate phytochemical profile accompanied by in vivo antinociceptive and anti-inflammatory screening of n-hexane (HE), dichloromethane (DME) and methanol (ME) extracts obtained from the aerial parts of the plant. The oral administration of ME (0.1, 0.3, 1 g/kg) caused a dose-related reduction (16.2, 42.1 e 70.2%) of acetic acid-induced abdominal writhing while HE and DME (1 g/kg, p.o.) were ineffective. In the hot plate test, ME (300 mg/kg, p.o.) increased the latency of heat stimulus between 30 and 120 min and inhibited the first (45%) and second (60%) phases of nociception in the formalin test. The antinociception induced by ME or positive control fentanyl (150 µg/kg, s.c.) in hot plate and formalin tests was prevented by naloxone (3 mg/kg, s.c.). When submitted to the carrageenan-induced peritonitis test, ME (0.5, 1.0, 2.0 g/kg, p.o.) impaired leukocyte migration into the peritoneal cavity by 46.8, 59.4 and 64.8% respectively, while positive control dexamethasone (2 mg/kg, s.c.), inhibited leukocyte migration by 71.1%. These results indicate that the antinociception obtained after oral administration of methanol extract of M. lindleyana involves anti-inflammatory mechanisms accompanied with opioid-like activity which could explain the use of the specie for pain and inflammatory diseases.