LQM10, a guanylhydrazone derivative, reduces nociceptive and inflammatory responses in mice.

In the present study, we examined the antinociceptive and anti-inflammatory activities of a guanylhydrazone derivative, (E)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-guanylhydrazone hydrochloride (LQM10), in mice. The antinociceptive effect was determined by assessing behavioural responses in different pain models, while anti-inflammatory activity was examined in carrageenan-induced pleurisy. Intraperitoneal LQM10 administration reduced the acetic acid-induced nociceptive behaviour, a phenomenon that was unaltered by pretreatment with yohimbine, atropine, naloxone or glibenclamide. In the formalin assay, LQM10 reduced nociceptive behaviour only in the second phase, indicating an inhibitory effect on inflammatory pain. LQM10 did not alter the pain latency in the hot plate assay and did not impact the locomotor activity of mice in the rotarod assay. In the carrageenan-induced pleurisy assay, LQM10 treatment inhibited critical events involved in inflammatory responses, namely, leucocyte recruitment, plasma leakage and increased inflammatory mediators (tumour necrosis factor Like Properties of Chalchones and Flavonoid Derivatives [TNF]-α and interleukin [IL]-1ß) in the pleural exudate. Overall, these results indicate that LQM10 exhibits antinociceptive effects associated with peripheral mechanisms and anti-inflammatory activity mediated via a reduction in leucocyte migration and proinflammatory mediators, rendering this compound a promising candidate for treating pain and inflammatory process.

Synthesis of Esters Containing Cinnamoyl Motif with Potential Larvicide Action: A Computational, Ecotoxicity and in Vitro Cytotoxicity Assessments.

An increasing morbidity and mortality rate has been related to arboviruses transmitted by Aedes aegypti. Compounds with cinnamoyl moiety represent an alternative against mosquitos, considering their larvicidal activity. This study aimed to assess the larvicidal activity of cinnamic ester derivates against Aedes aegypti larvae, along with evaluating their toxicity effect to assess its safety as a larvicide. Ethyl cinnamate demonstrated larvicidal activity (LC50 =48.59 µg/mL). Morphological changes in larvae were detected, as a degenerative response in the thorax. Through molecular docking, the molecular binding mode between 3b, 3c, and acetylcholinesterase showed strong hydrogen bond interactions. Preliminary in vitro cell viability revealed the non-cytotoxicity of 3c. Ecotoxicity results indicated a sensitivity of Artemia salina to cinnamic esters. The phytotoxicity bioassays show potential for cinnamic compounds to enhance germination and root development. These findings suggest that compound 3c is more suitable as a larvicide since it demonstrated low toxicity.

Modulation of interleukin expression by medicinal plants and their secondary metabolites: A systematic review on anti-asthmatic and immunopharmacological mechanisms.

BACKGROUND: Asthma is one of the most common chronic inflammatory conditions of the lungs in modern society. Asthma is associated with airway hyperresponsiveness and remodeling of the airways, with typical symptoms of cough, wheezing, shortness of breath and chest tightness. Interleukins (IL) play an integral role in its inflammatory pathogenesis. Medicinal herbs and secondary metabolites are gaining considerable attention due to their potential therapeutic role and pharmacological mechanisms as adjunct tools to synthetic bronchodilator drugs. PURPOSE: To systematically review the literature on the use of single or mixed plants extracts therapy in vivo experimental systems for asthma, emphasizing their regulations on IL production to improve lung. METHODS: Literature searches were performed on PubMed, EMBASE, Scopus and Web of Science databases. All articles in English were extracted from 1999 up to September 2019, assessed critically for data extraction. Studies investigating the effectiveness and safety of plant extracts administered; inflammatory cell count, immunoglobulin E (IgE) production and regulation of pro-inflammatory cytokine and T helper (Th) 1 and Th2-driven cytokine expression in bronchoalveolar lavage fluid (BALF) and lung of asthmatic animals were included. RESULTS: Four hundred and eighteen publications were identified and 51 met the inclusion criteria. Twenty-six studies described bioactive compounds from plant extracts. The most frequent immunopharmacological mechanisms described included reduction in IgE and eosinophilic recruitment, decreased mucus hypersecretion and airway hyperreactivity, enhancement of the balance of Th1/Th2 cytokine ratio, suppression of matrix metallopeptidase 9 (MMP-9) and reversal of structural alterations. CONCLUSION: Plant extract therapies have potential control activities on asthma symptoms by modulating the secretion of pro-inflammatory (IL-1ß, IL-8), Th17 (IL-17), anti-inflammatory (IL-10, IL-23, IL-31, IL-33), Th1 (IL-2, IL-12) and Th2 (IL-4, IL-5, IL-6, IL-13) cytokines, reducing the level of biomarkers of airway inflammation.

Antinociceptive and anti-inflammatory effect of Poincianella pyramidalis (Tul.) L.P. Queiroz.

ETHNOPHARMACOLOGY RELEVANCE: Poncianella pyramidalis (Leguminosae) is a Caatinga plant used in folk medicine because of its pharmacological properties, which include anti-inflammatory action. However, chemical compounds responsible for this effect have not yet been identified. AIM OF THE STUDY: This study aimed to evaluate the antioxidant, antinociceptive and anti-inflammatory effects of the ethyl acetate fraction from the inner bark of P. pyramidalis. MATERIAL AND METHODS: Total phenol content (TP) was estimated using the Folin-Ciocalteu reagent, while in vitro antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Chemical identification was done using LC-PDA/MS and LC-ESI/MS/MS. In vivo antinociceptive and anti-inflammatory properties were investigated using formalin, mechanical hypernociception and carrageenan-induced pleurisy assays in mice. RESULTS: TP was 525.08 ± 17.49 µg mg-1 gallic acid equivalent. The ethyl acetate fraction (EAF) inhibited 87.76% of the DPPH radical with an EC50 of 22.94 µg mL-1 and Antioxidant Activity Index of 1.74. LC-PDA/MS and LC-ESI/MS/MS identified 15 compounds that are mostly derived from gallic and ellagic acids. Regarding in vivo antinociceptive and anti-inflammatory activity, EAF (100 mg kg-1) significantly reduced the nociceptive response in the second phase of the formalin assay by 50% (p < 0.01) compared with the control group. In the hypernociception test, a significant (p < 0.001) anti-hyperalgesic effect of EAF (100 mg kg-1) was observed up to the third hour of evaluation (p < 0.001). In the carrageenan assay, EAF (100 mg kg-1) was shown to inhibit protein extravasation, increase total leukocytes and neutrophils, and inhibit mononuclear cells. CONCLUSION: These results demonstrate EAF from the inner bark of P. pyramidalis has strong in vitro antioxidant effect as well as in vivo antinociceptive and anti-inflammatory activities, which may be attributed to the bark being rich in phenolic compounds derived from gallic acid.

The Use of Medicinal Plants in Maceió, Northeastern Brazil: An Ethnobotanical Survey.

Background: The purpose of this study was to record and analyze the knowledge of medicinal plant use in the community in urban areas of Maceió city, Brazil. Methods: A total of 113 patients from the basic healthcare unit were assessed. Results: Approximately 95% of the interviewed stated that the plants were used for medicinal purposes. The majority of respondents were women (94.7%) who were between 51-60 years of age. Forty-eight plant species belonging to 28 families were cited as useful for medicinal purposes. The main families encountered were Lamiaceae (16.6%), Asteraceae (8.3%), Myrtaceae (6.2%), Fabaceae (6.2%), Annonaceae (4.1%), Laureaceae (4.1%), Rutaceae (4.1%), and Zingiberaceae (4.1%). These plants were used to treat a wide range of disturbances, including gastrointestinal, respiratory, and cardiovascular diseases. The majority of the respondents used decoctions of leaves that were cultivated in house (58.4%) to make their herbal preparations. The respondents revealed that medicinal plant preparations were safe and unaware of that are risks associated with their use. Conclusions: Medicinal plants still play an important role in the medical practices of the urban population from Maceió, Brazil. Our results highlight the importance of these plants for local people and indicate the need for further scientific investigations to validate their use as a complementary therapy for disease control.

Drug-induced anti-inflammatory response in A549 cells, as detected by Raman spectroscopy: a comparative analysis of the actions of dexamethasone and p-coumaric acid.

Corticosteroids are widely used as effective treatments for the control of chronic inflammatory diseases. However, because their long-term administration carries serious consequences, there is a need to investigate alternative therapies to reduce or even replace their use. In this regard, phenolic compounds have been presented as an alternative for the treatment of inflammatory diseases. p-Coumaric acid, a natural phenolic compound found throughout nature, exhibits antioxidative and anti-inflammatory properties. Herein, using a combination of Raman spectroscopy with principal component analysis and hierarchical cluster analysis, the inflammatory process induced by cigarette smoke extract (CSE) in epithelial cells treated with either a corticosteroid or p-coumaric acid was monitored in vitro. Our findings showed that p-coumaric acid had a significant anti-inflammatory effect in CSE-activated epithelial cells, and thus may be a useful alternative to corticosteroids for the treatment of airway inflammation in chronic obstructive pulmonary disease. In addition, multivariate analysis of the cell spectral data indicated that the mechanisms of action of the two drugs occur through different routes.

Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea.

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1ß, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 µg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

Isolation of a dihydrobenzofuran lignan, icariside E4, with an antinociceptive effect from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark.

The antinociceptive activity of icariside E4, a dihydrobenzofuran-type lignan isolated from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark, was evaluated in mice by using chemical and thermal models of nociception. Intraperitoneal (i.p.) administration of crude T. roseo-alba bark extract and its methanol fraction inhibited acetic acid-induced abdominal constriction in mice. Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of icariside E4 reduced the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6%, respectively. Icariside E4 administration had no effect in the first phase of the formalin test, but it reduced nociceptive behavior in the second phase as indicated by a reduction in the licking time. Icariside E4 did not modify thermal nociception in the hot-plate test model, suggesting that it had a peripheral antinociceptive action. The antinociceptive effect of icariside E4 in the writhing test was reversed by pre-administration of glibenclamide, but not of naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated that the antinociceptive activity of icariside E4 from T. roseo-alba in models of chemical pain occurred through ATP-sensitive K(+) channel-dependent mechanisms.

Evaluation of wound healing and antimicrobial properties of aqueous extract from Bowdichia virgilioides stem barks in mice.

The decoction of the stem barks from Bowdichia virgilioides KUNTH is a folk remedy used to treat inflammatory disorders in Latin American and Brazil. In the present study, the wound healing activity of aqueous extract of the stem bark from B. virgilioides, called AEBv, was evaluated by the rate of healing by wound contraction and period of epithelization at different days post-wound using the wound excisional model. On day 9, the AEBv-treated animals exhibited significative reduction in the wound area when compared with controls. In wound infected with S. aureus, the AEBv significantly improved the wound contraction when compared to the saline-treated mice. The histological analysis showed that AEBv induced a collagen deposition, increase in the fibroblast count and few inflammatory cells than compared to saline-treated group. The expression of collagen type I was increased in the group treated with AEBv as indicated by immunohistochemical staining. In vitro, the AEBv was effective only against S. aureus but not against P. aeruginosa. Together, the results of this study demonstrate, for the first time, the healing and antimicrobiological effects of aqueous extract of the stem bark from B. virgilioides in the therapy of skin wounds.

Anxiolytic-like effect of the extract from Bowdichia virgilioides in mice

Current therapeutic for the treatment of anxiety is associated with a wild variety of side effects. The traditional use of plant extract to health care can indicate an important source of new pharmaceuticals. Bowdichia virgilioides Kunth, Fabaceae, is a plant commonly employed in the Brazilian folk medicine to treat inflammatory conditions. Nevertheless, despite its popular use there are no studies related to its possible neuropharmacological effect. Here, we investigated the possible anxiolytic effect of the extract of B. virgilioides after acute and sub-chronic treatment in mice. The aqueous extract from the stem barks of B. virgilioides (20, 200 or 400 mg/kg) was orally administered, and its anxiolytic effect was evaluated in the elevated plus maze, open-field and rota-rod tests. Diazepam was employed as standard drug. The aqueous extract treatment was effective in inducing anxiolytic effects with single acute treatment, a phenomenon that remained after chronic treatment. However, no changes in spontaneous locomotor activity or myorelaxant effect after aqueous extract treatment. The extract was either safe with no deaths in mice treated orally with 1000 mg/kg. These findings suggest that the aqueous extract from the stem barks of Bowdichia virgilioides has an acute and sub-chronic anxiolytic-like effect without compromising motor activity, demonstrating an advantage regarding to antidepressant drugs.

Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent.

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

Potentiated anti-inflammatory effect of combined 780 nm and 660 nm low level laser therapy on the experimental laryngitis.

Reflux laryngitis is a common clinic complication of nasogastric intubation (NSGI). Since there is no report concerning the effects of low level laser therapy (LLLT) on reflux laryngitis, this study aimed to analyze the protective effect of single and combined therapies with low level laser at the doses of 2.1J and 2.1+1.2 J with a total irradiation time of 30s and 30+30 s, respectively, on a model of neurogenic reflux laryngitis. NSGI was performed in Wistar rats, assigned into groups: NGI (no treatment), NLT17.5 (single therapy), and NLT17.5/10.0 (combined therapy, applied sequentially). Additional non-intubated and non-irradiated rats were use as controls (CTR). Myeloperoxidase (MPO) activity was assessed by colorimetric method after the intubation period (on days 1, 3, 5, and 7), whereas paraffin-embedded laryngeal specimens were used to carry out histopathological analysis of the inflammatory response, granulation tissue, and collagen deposition 7 days after NSGI. Significant reduction in MPO activity (p<0.05) and in the severity of the inflammatory response (p<0.05), and improvement in the granulation tissue (p<0.05) was observed in NLT17.5/10.0 group. Mast cells count was significantly decreased in NGI and NLT17.5 groups (p<0.001), whereas no difference was observed between NLT17.5/10.0 and CTR groups (p>0.05). NLT17.5/10.0 group also showed better collagenization pattern, in comparison to NGI and NLT17.5 groups. This study suggests that the combined therapy successfully modulated the inflammatory response and collagenization in experimental model of NSGI-induced neurogenic laryngitis.

Antinociceptive and anti-inflammatory effects of octacosanol from the leaves of Sabicea grisea var. grisea in mice.

Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.

Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents.

We describe the antinociceptive and anti-inflammatory properties of citronellol (CT) in rodents. CT, a monoterpene alcohol, is a naturally occurring monoterpene compound prevalent in essential oils of various aromatic plant species, such as Cymbopogon citratus. In mice, when evaluated against acetic-acid-induced abdominal writhing, CT (25, 50 and 100 mg/kg, i.p.) reduced (P < 0.001) the amount of writhing compared to the control group. In the formalin test, CT also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking (P < 0.001). When assessed in a thermal model of pain, CT (100 mg/kg, i.p.) caused a significant increase (P < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be caused by motor abnormality. The anti-inflammatory activity of CT was investigated through carrageenan-induced pleurisy in mice. Pretreatment with CT was able to inhibit both neutrophil infiltration and the increase in TNF-α level in the exudates from carrageenan-induced pleurisy. In in vitro experiments, CT (1 and 100 µg/ml) also decreased nitric oxide production by LPS-stimulated macrophage. Together, these results indicate that CT is effective as an analgesic compound in various pain models, with its action probably mediated by the inhibition of peripheral mediators as well as central inhibitory mechanisms that could be related to its strong antioxidant effect observed in vitro.

Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models.

The present study was carried out to investigate the anti-inflammatory effect of the hexane extract of the leaves from Clusia nemorosa G. Mey, called HECn, using carrageenan-induced mice pleurisy and cotton pellet-induced mice granuloma. Additionally, the ability of HECn to affect both neutrophil migration as viability was investigated by use of the Boyden chamber assay and flow cytometry, respectively. The HECn significantly inhibited exudation, total leukocytes and neutrophils influx, as well as TNFα levels in carrageenan-induced pleurisy. However, the extract not suppressed the granulomatous tissue formation in the cotton pellet-induced granuloma test. Experiments performed in vitro revealed that HECn on human neutrophils inhibited a dose-dependent manner the CXCL1-induced neutrophil chemotaxis. Furthermore, HECn also inhibited the chemoattraction of human neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet activating factor (PAF) in a Boyden chamber. However, this same treatment not was able to induce apoptosis. The results obtained in this study showed that the extract from leaves of C. nemorosa possess a potent inhibitory activity in acute model of inflammation, being the effects mediated, in part, by inhibition of neutrophil responsiveness. These results indicate that C. nemorosa could be a good source for anti-inflammatory compounds.

Carvacrol attenuates mechanical hypernociception and inflammatory response.

Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 µg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.

Antinociceptive activity of aqueous extract of Bowdichia virgilioides in mice.

Bowdichia virgilioides Kunth (Family Fabaceae) is a plant that is distributed widely in the tropical and subtropical regions of the world. In the northeast region of Brazil, where B. virgilioides is called "sucupira-preta," the stem bark is used in folk medicine to treatment of inflammatory and painful diseases. This study aimed to evaluate the antinociceptive activity of the aqueous extract of the dried stem bark of B. virgilioides. The aqueous extract of B. virgilioides in doses of 50, 100, 200, and 400 mg/kg was administered orally 1 hour prior to pain induction. Only the doses of 200 and 400 mg/kg produced an inhibition by 61% and 74%, respectively, in the number of abdominal writhings induced by acetic acid. This antinociceptive effect was not reversed by pretreatment with naloxone, indicating that the effect is not associated with the activation of opioid receptors. In the formalin test, using the two highest doses, the extract had no effect in the first phase but produced an analgesic effect on the second phase with the inhibition of licking time (P < .001). In the hot plate test, no effect was seen at the dose of 400 mg/kg p.o. Our findings show that B. virgilioides contains pharmacologically active constituents that possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.

Computational models in plant-pathogen interactions: the case of Phytophthora infestans.

BACKGROUND: Phytophthora infestans is a devastating oomycete pathogen of potato production worldwide. This review explores the use of computational models for studying the molecular interactions between P. infestans and one of its hosts, Solanum tuberosum. MODELING AND CONCLUSION: Deterministic logistics models have been widely used to study pathogenicity mechanisms since the early 1950s, and have focused on processes at higher biological resolution levels. In recent years, owing to the availability of high throughput biological data and computational resources, interest in stochastic modeling of plant-pathogen interactions has grown. Stochastic models better reflect the behavior of biological systems. Most modern approaches to plant pathology modeling require molecular kinetics information. Unfortunately, this information is not available for many plant pathogens, including P. infestans. Boolean formalism has compensated for the lack of kinetics; this is especially the case where comparative genomics, protein-protein interactions and differential gene expression are the most common data resources.