Graciomar C. Costa

Brazilian Green Propolis: Anti-Inflammatory Property by an Immunomodulatory Activity

The immunomodulatory and anti-inflammatory activities of green propolis extracts from Apis mellifera were investigated using acute and chronic inflammation models. Swiss mice were anesthetized and a cotton pellet granuloma was implanted in subcutaneous tissue. Then the mice were divided into six groups and received apyrogenic water or different propolis extracts by oral route (5 mg/kg). According to the treatment the groups were designated as E1A, E1B, E10, E11, and E12. The control group received apyrogenic water. The treatment was performed by six days when the mice were killed. The blood and the bronchoalveolar lavage (BAL) were collected to measure the leukocyte recruitment. In acute pulmonary inflammation, Balb/c mice received lipopolysaccharide (LPS) of Escherichia coli by intranasal route for three days. Concomitantly the mice received by oral route apyrogenic water (control) or E10 and E11 propolis extracts. BAL was performed to assess the inflammatory infiltrate and cytokine quantification. The results showed that the E11 extract has anti-inflammatory property in both models by the inhibition of proinflammatory cytokines and increase of anti-inflammatory cytokines suggesting an immunomodulatory activity.

Avaliação da atividade leishmanicida in vitro de plantas medicinais

Searching for new leishmanicidal agents, promastigotes forms of L. amazonensis were cultured with the hydroalcoholic extracts obtained from the Tephrosia cinerea (L.) Pers. (Fabaceae), Dichorisandra sp (Commelinaceae), Syzygium jambolanum DC. (Myrtaceae), Julocroton triqueter (Lam.) Didr. var. triqueter (Euphorbiaceae), Passiflora edulis Sims(Passifloraceae), Cecropia sp (Cecropiaceae), Chenopodium ambrosioides L.(Chenopodiaceae), Pedilanhus tithymaloides (L.) Poit (Euphorbiaceae), Peristrophe angustifolia Nees(Acanthaceae) leaves and the aqueous extract obtained from the Orbignya phalerata Mart. (Arecaceae) mesocarp flour. The in vitro assay was performed with promastigotes incubated during 24 hours with 31.3, 62.5, 125.0, 250.0 and 500.0 µg/mL of each extract. Then the inhibitory concentration of the parasite growth (IC50) was determined. The effectiveness of J. triqueter, Dichorisandra sp and T. cinerea hydroalcoholic extracts to induce promastigotes death was intense since the IC50 were 29.5; 32.9 and 43.6 µg/mL, respectively. P. edulis, C. ambrosioides and S. jambolanum extracts had moderated effectiveness since the IC50 were 150.1; 151.9 and 166.6 µg/mL, respectively. P. tithymaloides and O. phalerata extracts showed a low efficacy in comparison with IC50 >500 µg/mL. Peristrophe angustifolia and Cecropia sp extracts had no leishmanicidal effect. Thus, three of the ten extracts that were tested showed a significant in vitro leishmanicidal activity.

Cytokines and visceral leishmaniasis: a comparison of plasma cytokine profiles between the clinical forms of visceral leishmaniasis

It is not well established whether cytokine production differs in response to different clinical forms of visceral leishmaniasis (VL). In this work, we performed a cross-sectional study to investigate the plasma levels of cytokines [interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10 and IL-12] involved in the pathogenesis of VL in 80 subjects from VL endemic areas, including subjects with active VL, subjects with asymptomatic infection, subjects with cured VL and uninfected controls. The patients were recruited by sampling from a referral hospital and by random selection from a population-based cohort study. The results showed significant differences in the plasma concentration of all cytokines between the groups (p < 0.05). Patients with the active disease had higher plasma levels of IL-10, IL-4, INF-γ and TNF-α relative to the other groups and they produced more IL-12 than asymptomatic and cured subjects. Only the IL-2 concentration was higher in the asymptomatic and cured subjects relative to the patients with active disease (p < 0.05). Our results suggest that these cytokines can be used as markers in epidemiological studies conducted in endemic areas to distinguish between different clinical forms of VL. However, their usefulness should be confirmed in investigations conducted in other endemic areas.

Efeito leishmanicida in vitro de Stachytarpheta cayennensis (Rich.) Vahl (Verbenaceae)

Leishmanicidal activity of the hydroalcoholic extract of Stachytarpheta cayennensis, species that is usually employed in ulcers caused by Leishmania, was evaluated in vitro using Leishmania braziliensis and L. amazonensis promastigotes forms. The hydroalcoholic extract was prepared from dried leaves and used in L. amazonensis and L. braziliensis promastigotes cultures at concentrations of 500 to 32.5 aeg/mL. After 24 hours the promastigotes forms were quantified and the IC50 was calculated. The cytotoxicity of the extract was evaluated using peritoneal macrophages. The extract presented a dose and specie-dependent leishmanicidal effect to Leishmania promastigotes, mainly to the L. braziliensis ones. The cytotoxic effect was not observed in macrophage cultures. In conclusion, the hydroalcoholic extract of S. cayennensis inhibits the growing of Leishmania promastigotes forms in vitro accounting for the folk use of this vegetal in skin ulcers caused by Leishmania.

Mechanisms underlying hypertriglyceridemia in rats with monosodium l-glutamate-induced obesity: Evidence of XBP-1/PDI/MTP axis activation

Non-alcoholic fatty liver disease (NAFLD) is intimately associated with insulin resistance and hypertriglyceridemia, whereas many of the mechanisms underlying this association are still poorly understood. In the present study, we investigated the relationship between microsomal triglyceride transfer protein (MTP) and markers of endoplasmic reticulum (ER) stress in the liver of rats subjected to neonatal monosodium L-glutamate (MSG)-induced obesity. At age 120 days old, the MSG-obese animals exhibited hyperglycemia, hypertriglyceridemia, insulin resistance, and liver steatosis, while the control (CTR) group did not. Analysis using fast protein liquid chromatography of the serum lipoproteins revealed that the triacylglycerol content of the very low-density lipoprotein (VLDL) particles was twice as high in the MSG animals compared with the CTR animals. The expression of ER stress markers, GRP76 and GRP94, was increased in the MSG rats, promoting a higher expression of X-box binding protein 1 (XBP-1), protein disulfide isomerase (PDI), and MTP. As the XBP-1/PDI/MTP axis has been suggested to represent a significant lipogenic mechanism in the liver response to ER stress, our data indicate that hypertriglyceridemia and liver steatosis occurring in the MSG rats are associated with increased MTP expression.

Efeito do tratamento com própolis de Scaptotrigona aff. postica sobre o desenvolvimento do tumor de Ehrlich em camundongos

Neste trabalho foi investigado o efeito do extrato hidroalcoolico de propolis (EHP) de Scaptotrigona aff. postica sobre o desenvolvimento do tumor de Ehrlich na forma solida, sobre a celularidade dos orgaos linfoides dos animais portadores de tumor, bem como, sobre a producao de oxido nitrico (NO) pelos macrofagos destes animais. Camundongos Swiss foram divididos em quatro grupos: controle, EHP 0,5; EHP 5 e EHP 50, os quais foram tratados por via intraperitoneal com dose unica de solucao salina (NaCl 0,9%); 0,5; 5 ou 50 mg de EHP/kg de animal, respectivamente. Depois de 48 h do tratamento, os animais foram inoculados com 105 celulas do tumor de Ehrlich nas patas. Os resultados mostraram que o tratamento com EHP nas doses de 5 e 50 mg/kg inibiu de forma significativa o desenvolvimento do tumor a partir do 6o dia pos-inoculo quando comparado ao controle e ao EHP 0,5. Alem disso, houve aumento significativo da celularidade do baco e da medula ossea nos grupos EHP 0,5 e EHP 5 em relacao ao controle. A producao de NO estimulada com concanavalina A (ConA) apresentou uma significante diminuicao nos grupos tratados com EHP em relacao ao controle. Pode-se concluir que o tratamento com EHP apresentou efeito antitumoral quando administrado nas doses de 5 e 50 mg/kg, o que pode estar relacionado com a sua composicao quimica e com a inibicao da producao de NO.

Effects of stingless bee propolis on experimental asthma.

Bee products have been used empirically for centuries, especially for the treatment of respiratory diseases. The present study evaluated the effect of treatment with a propolis hydroalcoholic extract (PHE) produced by Scaptotrigona aff. postica stingless bee in a murine asthma model. BALB/c mice were immunized twice with ovalbumin (OVA) subcutaneously. After 14 days, they were intranasally challenged with OVA. Groups P50 and P200 received PHE by gavage at doses of 50 and 200 mg/kg, respectively. The DEXA group was treated with intraperitoneal injection of dexamethasone. The OVA group received only water. The mice were treated daily for two weeks and then they were immunized a second time with intranasal OVA. The treatment with PHE decreased the cell number in the bronchoalveolar fluid (BAL). Histological analysis showed reduced peribronchovascular inflammation after treatment with PHE especially the infiltration of polymorphonuclear cells. In addition, the concentration of interferon-γ (IFN-γ) in the serum was decreased. These results were similar to those obtained with dexamethasone. Treatment with S. aff postica propolis reduced the pathology associated with murine asthma due an inhibition of inflammatory cells migration to the alveolar space and the systemic progression of the allergic inflammation.

Effect of propolis of Scaptotrigona aff. postica on the development of the tumor of Ehrlich in mice

Neste trabalho foi investigado o efeito do extrato hidroalcoolico de propolis (EHP) de Scaptotrigona aff. postica sobre o desenvolvimento do tumor de Ehrlich na forma solida, sobre a celularidade dos orgaos linfoides dos animais portadores de tumor, bem como, sobre a producao de oxido nitrico (NO) pelos macrofagos destes animais. Camundongos Swiss foram divididos em quatro grupos: controle, EHP 0,5; EHP 5 e EHP 50, os quais foram tratados por via intraperitoneal com dose unica de solucao salina (NaCl 0,9%); 0,5; 5 ou 50 mg de EHP/kg de animal, respectivamente. Depois de 48 h do tratamento, os animais foram inoculados com 105 celulas do tumor de Ehrlich nas patas. Os resultados mostraram que o tratamento com EHP nas doses de 5 e 50 mg/kg inibiu de forma significativa o desenvolvimento do tumor a partir do 6o dia pos-inoculo quando comparado ao controle e ao EHP 0,5. Alem disso, houve aumento significativo da celularidade do baco e da medula ossea nos grupos EHP 0,5 e EHP 5 em relacao ao controle. A producao de NO estimulada com concanavalina A (ConA) apresentou uma significante diminuicao nos grupos tratados com EHP em relacao ao controle. Pode-se concluir que o tratamento com EHP apresentou efeito antitumoral quando administrado nas doses de 5 e 50 mg/kg, o que pode estar relacionado com a sua composicao quimica e com a inibicao da producao de NO.

Effect of propolis of Scaptotrigona aff. postica on the development of Ehrlich's tumour in mice.

Neste trabalho foi investigado o efeito do extrato hidroalcoolico de propolis (EHP) de Scaptotrigona aff. postica sobre o desenvolvimento do tumor de Ehrlich na forma solida, sobre a celularidade dos orgaos linfoides dos animais portadores de tumor, bem como, sobre a producao de oxido nitrico (NO) pelos macrofagos destes animais. Camundongos Swiss foram divididos em quatro grupos: controle, EHP 0,5; EHP 5 e EHP 50, os quais foram tratados por via intraperitoneal com dose unica de solucao salina (NaCl 0,9%); 0,5; 5 ou 50 mg de EHP/kg de animal, respectivamente. Depois de 48 h do tratamento, os animais foram inoculados com 105 celulas do tumor de Ehrlich nas patas. Os resultados mostraram que o tratamento com EHP nas doses de 5 e 50 mg/kg inibiu de forma significativa o desenvolvimento do tumor a partir do 6o dia pos-inoculo quando comparado ao controle e ao EHP 0,5. Alem disso, houve aumento significativo da celularidade do baco e da medula ossea nos grupos EHP 0,5 e EHP 5 em relacao ao controle. A producao de NO estimulada com concanavalina A (ConA) apresentou uma significante diminuicao nos grupos tratados com EHP em relacao ao controle. Pode-se concluir que o tratamento com EHP apresentou efeito antitumoral quando administrado nas doses de 5 e 50 mg/kg, o que pode estar relacionado com a sua composicao quimica e com a inibicao da producao de NO.