Maria Eline Matheus

Antineoplasic activity of Copaifera multijuga oil and fractions against ascitic and solid Ehrlich tumor.

The aim of this study was to investigate the effect of chronic treatment with C. multijuga oil on Ehrlich tumor evolution. C. multijuga was fractionated in a KOH impregnated silica gel column chromatography to give three distinct fractions, i.e., hexanic, chloroformic, and methanolic, mainly composed by hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes, respectively. Results demonstrated that the C. multijuga oil, the hexanic, and chloroformic fractions did not develop toxic effects. The oil, hexanic and chloroformic fractions (doses varying between 100 and 200mg/kg) showed antineoplasic properties against Ehrlich ascitic tumor (EAT) and solid tumor during 10 consecutive days of treatment inhibiting ascitic tumor cell number, reverting medulla and blood cell counts to values similar to control group, and inhibiting the increase on several inflammatory mediators (total protein, PGE(2), nitric oxide, and TNF) on ascitic fluid. The treatment also inhibited the increase in paw volume on tumor-inoculated mice. In conclusion, C. multijuga as well as its fractions demonstrated antineoplasic effect even after oral administration confirming its use by traditional medicine.

Characterization of the antinociceptive and anti-inflammatory activities of fractions obtained from Copaifera multijuga Hayne

ETHNOPHARMACOLOGICAL RELEVANCE Copaifera multijuga Hayne (Leguminosae) is a tree that produces an oleoresin, which is extensively commercialized in Brazil as capsules or crude oil for the treatment of several disorders. Ethnopharmacological studies show a diversity of indications such as anti-inflammatory and epidermal wound cicatrization. AIM OF THE STUDY In the present work three fractions obtained from Copaifera multijuga oleoresin (hexane (HF), chloroform (CF), and methanol (MF) from a KOH impregnated silica gel column chromatography, representing the three main classes of compounds in the Copaifera genus (hydrocarbon sesquiterpenes, oxygenated sesquiterpenes and acidic diterpenes), were evaluated using antinociceptive and anti-inflammatory models. MATERIALS AND METHODS HF, CF, and MF (doses ranging between 1 and 150 mg/kg, depending on the model used), Copaifera multijuga oleoresin (CMO, 100mg/kg, p.o.) and the reference drug morphine (5mg/kg, p.o.) were evaluated using models for analgesia (acetic acid-induced contortions and tail flick) or inflammation (rat paw oedema and increase in vascular permeability). To elucidate the mechanism of action from the fractions, animals were pre-treated with naloxone (opioid receptor antagonist, 5mg/kg, i.p.). RESULTS Fractions significantly inhibited (in a concentration-dependant way) the number of contortions induced by acetic acid and the second phase of formalin-induced licking response. Similar results were observed in the tail flick model. The central antinociceptive effect for HF and CF at the doses of 50 and 100mg/kg was higher than the one observed for morphine (1mg/kg). Administration of naloxone inhibited the antinociceptive effect of fractions indicating that HF, CF, and MF may be acting on opioid receptors. All three fractions also inhibited rat paw oedema and the increase in vascular permeability induced by several phlogistic agents (carrageenan, histamine, and serotonin). CONCLUSIONS Our results indicate that fractions obtained from Copaifera multijuga Hayne demonstrate an antinociceptive effect probably mediated by opioid receptors, and anti-inflammatory activity through inhibition of histaminergic and serotoninergic pathways.

The latex obtained from Hancornia speciosa Gomes possesses anti-inflammatory activity.

AIM OF THE STUDY Hancornia speciosa Gomes (Apocynaceae) is a tree that is widely distributed throughout Brazil. Its latex is collected and used extensively to treat acne, warts, diseases related to bursitis, and inflammation. In this work, we describe the anti-inflammatory effects of the latex. MATERIALS AND METHODS The latex from Hancornia speciosa (0.06-1.3mg/kg, p.o.) and the reference drug acetylsalicylic acid (ASA, 200mg/kg, p.o.) were evaluated in analgesia (formalin-induced licking, acetic acid-induced contortions, and hot plate) and inflammation models (formalin-induced licking, paw oedema, and subcutaneous air pouch, with measurement of cell migration, exudate volume, protein extravasations, nitric oxide, prostaglandin E2, TNF-α, and IL-6, and expression of the enzymes inducible nitric oxide synthase and cyclooxygenase 2). RESULTS The latex from Hancornia speciosa significantly inhibited the number of writhings and the time that the animal spent licking the formalin-injected paw (second phase). Doses of 0.1-1.3mg/kg latex reduced carrageenan-induced rat paw oedema. However, only the highest doses (0.6 and/or 1.3mg/kg) reduced the oedema induced by bradykinin, histamine, and serotonin. The latex also inhibited inflammation induced by subcutaneous carrageenan injection, cell migration, exudate volume, protein extravasations, increased levels of inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IL-6) produced in the pouch, and increased expression of the enzymes nitric oxide synthase and cyclooxygenase 2. CONCLUSIONS Our results indicate that the latex obtained from Hancornia speciosa demonstrates significant anti-inflammatory activity through the inhibition of nitric oxide, PGE2, and cytokine production, thus confirming the popular use of this plant as an anti-inflammatory agent.

Anti-inflammatory and analgesic activity of Bouchea fluminensis

Dried leaves extract from Bouchea fluminensis was assessed in anti-inflammatory (mouse paw edema) and analgesic models (acetic acid-induced writhings and hot plate). Oral pretreatment of animals with a crude mixture (IG) and a purified mixture of ursolic, oleanolic and micromeric acids (IG-59) at doses ranging from 1 to 30 mg/kg, significantly inhibited carrageenin-induced edema formation. At the same doses, IG and IG-59 also exhibited peripheral and central analgesic activity. It seems that B. fluminensis triterpenes develop their analgesic effect through central opioid receptors, due to the observation that naloxone reverted analgesic activity on the hot plate model.

Synthesis and in vivo evaluation of 5-chloro-5-benzobarbiturates as new central nervous system depressants

A new family of barbiturates, 5-chloro-5-benzylbarbituric acids, was prepared using a simple efficient synthetic method from aromatic aldehydes and barbituric acid, followed by reduction and chlorination with trichloro-isocyanuric acid, affording overall yields of 53 to 70%. The in vivo evaluation with mice showed that these compounds present tranquilizing activity.

Antinociceptive activity of (-)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid on acute pain in mice.

Pain is a major cause of distress, both physical and psychological. There is a continuous search for new pharmacologically active analgesic agents with minor adverse effects. Recently, the synthesis of (−)-(2S,6S)-(6-ethyl-tetrahydropyran-2-yl)-formic acid [tetrahydropyran derivative (TD)] was described. The objective of this study was to investigate antinociceptive effects of TD. Its activity was compared with the activity of morphine. The effects of TD and morphine were evaluated in models of inflammatory and noninflammatory pain. TD (6–1200 &mgr;mol/kg, intraperitoneally) significantly reduced the nociceptive effects induced by acetic acid or formalin in mice. TD also demonstrated an antinociceptive effect in the tail-flick and hot-plate model. The opioid receptor antagonist, naloxone (at 15 &mgr;mol/kg, intraperitoneally), reversed the antinociceptive activity of TD in all the models evaluated. Morphine and TD induced tolerance in mice. However, the onset of tolerance to TD was delayed compared with that induced by morphine. These results indicate that TD develops significant antinociceptive activity and, at least part of its effects seems to be mediated by the opioid system.

Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16(+), CCR5(+) and TLR8(+) monocytes.

Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT.

Phytochemical profile and analgesic evaluation of Vitex cymosa leaf extracts

Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.

Atividade analgésica e antiedematogênica de Polygala paniculata L. (Polygalaceae) selvagem e obtida por micropropagação

The ethanolic extracts of Polygala paniculata L. (Polygalaceae), wich is a herbaceous plant widely distributed all over Brazil, were tested for their analgesic effects using hot plate, tail flick and formalin test models, and for their antiedematogenic effects using croton oil induced ear oedema. The ethanolic extracts obtained from wild and micropropagated plants produced analgesic effects against thermal and chemical induced pain. The highest results were observed at the dose of 400 mg/kg. The inhibition of ear oedema in mice was also observed after treatment with ethanolic extract of Polygala paniculata. The effects produced by micropropagated plants were lower than wild plants, whereas both had produced significant effects. These results suggest that the ethanolic extracts from wild and micropropagated Polygala paniculata possess analgesic and antiedematogenic effects.

Ação de extratos do açaí (Euterpe oleracea Mart.) sobre a produção de óxido nítrico em células RAW 264.7

Acai (Euterpe oleracea Mart.) is a tropical palm tree appreciated for its attractive beauty and for nutritional purposes. Chemical studies have revealed the presence of fatty acids and steroids. In the present work, it has been tested the action of the extracts obtained from the fruits and flowers on the nitric oxide (NO) production, a very important molecule with a lot of physiological rules such as vasodilatation, neurotransmission, tumoricidal and cytotoxic activity. Cells RAW 264.7 stimulated with bacterial lipopolysaccharide (LPS, 100 ng/ml) and interferonalpha (IFN-alpha, 10 U/ml) produce large amounts of nitric oxide (35 μM) when compared with non-stimulated cells (3μM). The hexane, dichloromethane, ethyl acetate and n-butanol extracts have shown high inhibition capacity, concentration-dependent in the cells activated with LPS and IFN-alpha, and the highest concentration has promoted almost 100 % of inhibition. We also have tested if the inhibitory effect was due to a scavenger action using a NO donor, the SNAP. Only the ethyl acetate extract has shown significant scavenger action. At this moment an effort is going on to try to understand the possible mechanisms associated to the inhibition of those extracts.