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.

Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women.

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β1) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O2-) and hydrogen peroxide (H2O2) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O22, H2O2 and TNF-α, and lower levels of IL-10 and TGF-β1 than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O2- and H2O2 release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.

Acute aerocystitis in Piaractus mesopotamicus: Participation of eicosanoids and pro-inflammatory cytokines

A total of 360 pacus (Piaractus mesopotamicus) were used to study vascular permeability (VP) and inflammatory cell component (CC) in induced aerocystitis in P. mesopotamicus through inoculation of inactivated Aeromonas hydrophila, and the effect of steroidal and nonsteroidal anti-inflammatory drugs. It was observed that after inoculation of A. hydrophila, the maximum VP occurred 180 min post-stimulus (MPS). Pretreatment with anti-inflammatory drugs inhibited VP, and the inhibitory effect of dexamethasone was seen earlier than the effects caused by meloxicam and indomethacin. Inoculation of the bacterium caused a gradual increase in the accumulation of cells, which reached a maximum 24 h post-stimulus (HPS). Pretreatment with dexamethasone, indomethacin and meloxicam reduced the accumulation of lymphocytes, thrombocytes, granulocytes and macrophages. There was no significant difference between the different doses of the drugs tested. The results suggest that eicosanoids and pro-inflammatory cytokines participate in chemical mediation in acute inflammation in pacus. © 2013 Elsevier Ltd.

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.

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.

Efeitos de drogas antiplaquetárias na doença periodontal

The association between platelets, angiogenesis and progression or repair of periodontal disease has been little explored and, consequently, the results are inconclusive. The pathogenic bacteria present in the periodontal pocket release endotoxins that affect the endothelial integrity and are able to induce the production of chemical mediators derived from plasma proteins and blood clotting while altering platelet function. There is great interest in the modulation of platelet activity in vascular disorders, especially cardiovascular diseases. For this reason, antiplatelet drugs, that are commonly used in the prevention of thromboembolic diseases, such as myocardial infarction, ischemic stroke and peripheral arterial disease, have been used. Aspirin is the only non-steroidal antiinflammatory agent with antiplatelet activity. In the periodontium, instead of only reduces levels of inflammatory cytokines, also significantly affects bleeding on probing, suggesting a dose-dependent modulation of periodontitis. In contrast, clopidogrel and ticlopidine are thienopyridine drugs with no known antiinflammatory action, suggesting that this benefit is related to an antiinflammatory effect indirectly correlated to their antiplatelet activity already established. In the literature there is limited information about the effect of these drugs on periodontium and periodontal disease development. Antiplatelet drugs hypothetically can change both the pathogenesis of periodontitis and subsequent periodontal tissue repair by blocking the secretion of chemical mediators which in general are important in modulating inflammation and tissue repair.

Balancing Inflammatory, Lipid, and Xenobiotic Signaling Pathways by VSL#3, a Biotherapeutic Agent, in the Treatment of Inflammatory Bowel Disease

Background: The interleukin 10 knockout mouse (IL10-KO) is a model of human inflammatory bowel disease (IBD) used to Study host microbial interactions and the action of potential therapeutics. Using Affymetrix data analysis, important signaling pathways and transcription factors relevant to gut inflammation and antiinflammatory probiotics were identified.

Methods: Affymetrix microarray analysis on both wildtype (WT) and IL10-KO mice orally administered with and without the probiotic VSL#3 was performed and the results validated by real-time polymerase chain reaction (PCR), immunocytochemistry, proteomics, and histopathology. Changes in metabolically active bacteria were assessed with denaturing gradient gel electrophoresis (DGGE).

Results: Inflammation in IL10-KO mice was characterized by differential regulation of inflammatory, nuclear receptor, lipid, and xenobiotic signaling pathways. Probiotic intervention resulted in downregulation of CXCL9 (fold change [FC] = -3.98, false discovery rate [FDR] = 0.019), CXCL10 (FC = -4.83, FDR = 0.0008), CCL5 (FC -3.47 FDR = 0.017), T-cell activation (Itgal [FC = -4.72, FDR = 0.00009], Itgae [FC = -2.54 FDR = 0.0044]) and the autophagy gene IRGM (FC = -1.94, FDR = 0.01), a recently identified susceptibility gene in human IBD. Consistent with a marked reduction in integrins, probiotic treatment decreased the number of CCL5+ CD3+ double-positive T Cells and upregulated galectin2, which triggers apoptosis of activated T cells. Importantly, genes associated with lipid and PPAR signaling (PPAR alpha [FC = 2.36, FDR = 0.043], PPARGC1 alpha [FC 2.58, FDR = 0.016], Nrld2 [FC = 3.11, FDR = 0.0067]) were also upregulated. Altered microbial diversity was noted in probiotic-treated mice.

Conclusions: Bioinformatics analysis revealed important immune response. phagocytic and inflammatory pathways dominated by elevation of T-helper cell 1 type (TH1) transcription factors in IL10-KO mice. Probiotic intervention resulted in a site-specific reduction of these pathways but importantly upregulated PPAR, xenobiotic, and lipid signaling genes. potential antagonists of NF-kappa B inflammatory pathways.

Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.

PURPOSE:

To explore the potential association between adverse corneal events and the use of topical nonsteroidal antiinflammatory drugs (NSAIDs).

SETTING:

Practice-based reports.

METHODS:

A detailed case-reporting form and request for medical records were sent to all practices reporting cases of corneal or conjunctival pathology in association with the use of topical NSAIDs to the American Society of Cataract and Refractive Surgery. Cases were classified as "mild," "moderate," or "severe" according to predetermined clinical criteria.

RESULTS:

Records of 140 eyes (129 patients) were reviewed; 51 cases (36.4%) were mild, 55 (39.3%) moderate, and 34 (24.3%) severe. An association with a specific topical NSAID was confirmed in 117 cases (81.8%). Most confirmed cases (53.8%) involved generic diclofenac (Falcon). Cases associated with brand diclofenac (Voltaren, CIBA Vision) and ketorolac (Acular, Allergan) were more likely to have ocular comorbidity and to have received significantly higher total doses of NSAIDs. Neither "off-label" use nor use of any specific agent was associated with severe compared to mild or moderate disease. However, patients with more severe adverse events were more likely to have a history of diabetes, previous surgery in the affected eye, and surgery other than cataract. Cases not occurring in the perioperative period had significantly worse outcomes, had significantly more ocular comorbidities, and received nearly 3 times the dose of NSAIDs.

CONCLUSIONS:

While topical NSAIDs as a class may be associated with severe adverse events, such events appeared to require potentiation in the form of high total doses, ocular comorbidities, or both with Acular and Voltaren. Severe adverse events might have been more likely to occur at lower doses and in routine postoperative settings with generic diclofenac.

Antidiarrheal and intestinal antiinflammatory activities of a methanolic extract of Qualea parviflora Mart. in experimental models

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)