Marcia Regina Piuvezam

Anti-inflammatory activity of alkaloids: a twenty-century review

Many substances which interfere with the inflammatory response have been isolated from plants. This review shows some alkaloids of vegetal origin which in the period of 1907 to 2000 were evaluated regarding a possible anti-inflammatory activity. The alkaloids were classified in sub-groups in accordance with their chemical structures and the pharmacological data were obtained from different experimental models. Of the 171 evaluated alkaloids, 137 presented anti-inflammatory activity, and among those, the isoquinoline type was the most studied. The Carrageenin-induced paw edema was the most used model for evaluating the anti-inflammatory activity. In this review, 174 references were cited.

Anti-allergic effect of bee pollen phenolic extract and myricetin in ovalbumin-sensitized mice

ETHNOPHARMACOLOGICAL RELEVANCE The bee pollen is used in folk medicine to alleviate allergic reactions. The bee pollen phenolic extract (BPPE) consists in phenolic compounds (flavonoids) from plants picked by Apis mellifera bee. AIM OF THIS STUDY Here we evaluated the anti-allergic property of the BPPE and the flavonoid myricetin (MYR) in murine model of ovalbumin (OVA)-induced allergy. MATERIALS AND METHODS The study focused on the BPPE or myricetin treatment of OVA-sensitized BALB/c mice and their effects on the IgE and IgG1 production, pulmonary cell migration, eosinophil peroxidase (EPO) activity and anaphylactic shock reaction. RESULTS The BPPE treatment (200mg/kg) showed inhibition of the paw edema, IgE and IgG(1) OVA-specific production, leukocyte migration to the bronchoalveolar lavage (BAL) and EPO activity in lungs. In addition, BPPE treatment showed partial protection on the anaphylactic shock reaction induced by OVA. Treatment with myricetin (5 mg/kg) also inhibited pulmonary cell migration and IgE and IgG(1) OVA-specific production. CONCLUSIONS These results support the hypothesis the myricetin is one of the flavonoids of BPPE responsible for the anti-allergic effect and a potential tool to treat allergies.

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and thermal hyperalgesic reactions in sensitized animals.

Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for the treatment of airway respiratory diseases. A murine model of immediate allergic reaction was used to evaluate warifteine treatment in the IgE production, leukocyte activation, thermal hyperalgesia, mast cell degranulation and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h before OVA sensitization reduced OVA induced paw edema as well as the OVA-specific IgE serum titers as compared with non-treated and OVA-sensitized animals. Warifteine also reduced the mice death evoked by IgE-dependent anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess the effect of warifteine treatment on T cell proliferative response, spleen cells from warifteine treated or non-treated and OVA-sensitized animals were evaluated. Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate following OVA stimulation as compared with spleen cell cultures from non-treated animals. This response may be related with the increase of NO production as observed in peritoneal macrophage cultures treated with warifteine. Thermal hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0 microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after DNP-BSA challenge measured by histamine release. In addition, compound 48/80-induced scratching behavior was also sensitive to warifteine treatment. These results demonstrate for the first time that warifteine treatment reduced the allergy-associated responses.

Effect of the activity of the Brazilian polyherbal formulation: Eucalyptus globulus Labill, Peltodon radicans Pohl and Schinus terebinthifolius Radd in inflammatory models

The Brazilian polyherbal formulation (BPF) is composed by dyes of Eucalyptus globulus Labill, Peltodon radicans Pohl and Schinus terebinthifolius Raddi in alcohol at 13.3° GL. The formulation is popularly used in Paraiba state, Brazil since 1889 and it is used as an antiseptic and anti-inflammatory medicine. The aim of this study was to evaluate the anti-inflammatory property of the polyherbal formulation. For this purpose it was used the12-O-tetradecanoylphorbol 13-acetate (TPA) and capsaicin-induced mouse ear edema and the carrageenan-induced rat paw edema. The BPF at dose of 26 mL/Kg inhibited both 12-O-tetradecanoylphorbol 13-acetate (TPA) and capsaicin-induced ear edema by 49% (p < 0.05) and 24% (p < 0.01) respectively. Preliminary results on carrageenan-induced rat paw edema demonstrated that oral administration also inhibited the paw edema by approximately 29%. The results demonstrate that the Brazilian polyherbal formulation has anti-inflammatory activity and the better dose was the one used by the population.

Cissampelos sympodialis Eichl. leaf extract increases the production of IL-10 by concanavalin-A-treated BALB/c spleen cells.

The effect of the aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl. (Menispermaceae) leaves (AFL) on Concanavalin-A (Con-A)-activated spleen cell proliferation and cytokine (IL-2, IL-4, IL-10 and IFN-gamma) secretion were analyzed. BALB/c spleen cells were treated, in vitro, with different concentrations, ranging from 6.25 to 400 microg/ml of AFL either in the presence or the absence of 5 microg/ml of the mitogen Con-A. It was observed that concentrations of the AFL higher then 50 microg/ml were toxic to the cells and concentrations ranging from 6.25 to 50 microg/ml decreased the lymphocyte proliferative response in the presence of the mitogen. This inhibition of mitogen induced proliferation was not reverted by the addition of exogenous recombinant IL-2. The AFL did not significantly inhibit IL-2 secretion. In the presence of AFL there was a reduction in the levels of secreted IFN-gamma while the production of both IL-10 and IL-4 were increased. AFL did not induce the production of any of the cytokines analyzed, in the absence of Con-A. It is suggested that increased IL-10 production down regulates IFN-gamma secretion and T cell proliferative responses.

Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease.

Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-d-glycopiranosil-(1-->6)-alpha-l-ramnopiranosil]-7-O-alpha-l-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effect, GRRK was administered 1h (hour) before each OVA-sensitization and challenge, while to analyze the curative effect, mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset of AAD was evaluated 24h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore, GRRK has a potential clinical use for the treatment of allergic asthma.

Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in airway hyperreactivity and lung remodeling in a mouse model of asthma

BACKGROUND Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis root bark is largely used in the indigenous and folk medicine to treat several inflammatory disorders, including asthma. Asthma is a chronic inflammatory allergic disease characterized by airway hyperreactivity (AHR), eosinophil tissue infiltration and lung remodeling. The aim of this study was to evaluate the therapeutic effect of C. sympodialis and its isolated alkaloid warifteine on allergen triggered airway hyperreactivity (AHR) and lung remodeling in murine model of asthma. METHODOLOGY/PRINCIPAL FINDINGS The oral pre-treatment with C. sympodialis or warifteine inhibited allergen-induced AHR to inhaled methacholine and IL-13 levels in the bronchoalveolar lavage (BAL). In order to investigate the therapeutic potential of C. sympodialis and warifteine, animals were treated 1h after the last ovalbumin (OVA) challenge in sensitized animals. Similarly to the pre-treatment, post-treatment with warifteine was effective to inhibit significantly AHR to inhaled methacholine and to reduce IL-13 levels in the BAL. In addition, oral pre- or post-treatments with C. sympodialis or warifteine reduced OVA-induced eosinophil tissue infiltration, mucus production and subepithelial fibrosis to values similar to nonallergic controls. CONCLUSIONS Our data show the anti-allergic and immunoregulatory properties of C. sympodialis, acting mostly through the active compound warifteine, to inhibit the airway hyperreactivity and lung remodeling through a mechanism at least partially dependent of IL-13 and eosinophil inhibition. Therefore placing warifteine as an interesting therapeutic candidate in allergic inflammation and corroborating the folk medicine use of C. sympodialis as anti-allergic plant.

Effects of Plant Extracts on HIV-1 Protease

Acquired immunodeficiency syndrome (AIDS) is one of the most important public health problems, affecting many people every day. This syndrome is caused by the human immunodeficiency virus (HIV) and the HIV-1 protease plays an essential role by promoting virus maturation and thus infecting new cells. The HIV-1 protease is one of the main targets for anti-HIV drug therapy. The present work is a literature survey of plant extracts whose activity has been studied on HIV-1 protease. Here we list 275 species of medicinal plants, distributed in 99 families, with their place of origin, part used, type of extract, concentration and activity. We aim with this work to provide data that could be used in the research and development of new therapeutic agents for AIDS treatment.

Salivary cortisol and frailty syndrome in elderly residents of long-stay institutions: A cross-sectional study

Analyze the relationship between frailty and cortisol in elderly residents of long-stay institutions. A cross-sectional study was conducted in the city of João Pessoa-PB-Brazil, on a sample of residents of long-stay institutions. Data were collected on frailty phenotype (weight loss, fatigue, slowness, weakness and low physical activity) and salivary cortisol (first measurement between 6 and 7a.m.; second measurement between 11 and 12a.m.; third measurement between 4 and 5p.m.). Statistical analysis applied Pearsons correlation test, Chi-square test, ANOVA and linear regression. The sample was composed of 69 elderly subjects, 37.7% men and 62.3% women, with a mean age of 77.5 (±7.8) years. The percentage of frail elderly was 45.8%. Frail aged subjects achieved higher cortisol values on the third measurement (p=0.04) and frailty load was significantly associated to the first measurement (r=0.25, p=0.04). Simple linear regression analysis showed a rate of determination (R(2)=0.05) between frailty load and the first cortisol measurement. Greater cortisol values in the morning and before bed among frail aged individuals suggest a positive correlation may exist between cortisol levels and frailty in elderly residents of long-stay institutions.