Anti-eosinophilic effect of Lafoensia pacari in toxocariasis.
We previously reported the anti-inflammatory activity of Lafoensia pacari extract in Toxocara canis infection, a model of systemic IL-5-dependent eosinophil migration. In the present study, we describe the kinetics of the antiinflammatory activity of L. pacari extract and compare
it with dexamethasone. T. canis-infected mice were submitted to different treatment protocols and the cells present in bronchoalveolar space and peritoneal cavity were collected at the end of each treatment period. The results showed that L. pacari extract effectively inhibited eosinophil migration only when the treatment was initiated before the peak of eosinophil migration (1st to 18th; 12th to 18th and 12th to 24th day post-infection). When eosinophil migration was established, administration of L. pacari extract had no effect on it (treatment 18th to 24th day post-infection). Dexamethasone was effective in inhibiting eosinophil migration in all periods studied. We suggest that L. pacari extract can potentially be a natural alternative treatment of eosinophilic diseases.
[C] 2007 Published by Elsevier GmbH.
Keywords: Lafoensia pacari; Toxocara canis; Dexamethasone; Eosinophils; Anti-inflammatory activity
The inflammatory responses to parasitic nematode infections and allergic diseases have some similarities. Toxocara canis-infected animals show blood and tissue eosinophilia (Beaver et al., 1952; Faccioli et al., 1998), increased total serum immunoglobulin E (IgE) levels (Brunello et al., 1983) and inflammation of the upper respiratory system (Buijs et al., 1994, 1995). For these reasons, infection by this parasite is commonly used as a model of asthma study. Glucocorticoids are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, all of which are associated with an increased expression of inflammatory genes (Eum et al., 1996; Frieri, 1999; Belvisi and Hele, 2003). Dexamethasone is routinely used to negatively modulate cell migration into the sites of inflammation, and this inhibition is accomplished, in part, by its potent effect on the synthesis of proinflammatory cytokines and chemokines coupled to a reduced degree of leukocyte responsiveness (van der Velden, 1998).
Natural products have long been used in folk medicine as alternative treatment for various diseases, including inflammatory processes of diverse origin. Many medicinal plants provide relief of symptoms comparable to that obtained with allopathic medicines. The majority of the clinically important medicines belong to steroidal or non-steroidal anti-inflammatory chemical therapeutics for treatment of several diseases. Although these drugs have potent activity, they also have various and severe adverse effects. Therefore, agents of natural origin with very few side-effects are required as substitutes for chemical therapeutics (Verpoorte, 1999). The Lythraceae family comprises three species that have verified anti-inflammatory properties. Lawsone and cryogenine, compounds respectively isolated from Lawsonia inermis and Heimia salicifolia, have been shown to exhibit anti-inflammatory activity in several models (Kaplan et al., 1967; Watson and Malone, 1977; Ali et al., 1995). Lafoensia pacari is known in the state of Mato Grosso (Brazil) as 'mangava brava' or 'dedaleira', and has been used in traditional medicine to treat gastric ulcers and inflammation (Albuquerque et al., 1996; Solon et al., 2000). In a previous study, the experimental murine model of toxocariasis was used to evaluate the anti-inflammatory activity of an ethanolic extract of L. pacari stem bark. We demonstrated in this model of allergic asthma (Kay et al., 1985), a reduction in the number of eosinophils in the peritoneal cavity, bronchoalveolar fluid, blood and bone marrow in T. canis-infected mice treated with an aqueous suspension from the ethanolic extract of L. pacari. Moreover, the reduced levels of IL-5 observed in serum, lung homogenates and bronchoalveolar fluid demonstrated the anti-inflammatory mechanisms of L. pacari (Rogerio et al., 2003). This cytokine is involved with terminal differentiation, proliferation and activation of eosinophils (Yamaguchi et al., 1988) and induces eosinophil release from bone marrow to the peripheral blood (Faccioli, et al., 1996).