Treatment with triterpenic fraction purified from Baccharis uncinella leaves inhibits Leishmania (Leishmania) amazonensis spreading and improves Th1 immune response in infected mice

Abstract

The current medications used to treat leishmaniasis have many side effects for patients; in addition, some cases of the disease are refractory to treatment. Therefore, the search for new leishmanicidal compounds is indispensable. Recently, it was demonstrated that oleanolic- and ursolic-containing fraction from Baccharis uncinella leaves eliminated the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and L. (Viannia) braziliensis without causing toxic effects for J774 macrophages. Thus, the aim of the present work was to characterize the therapeutic effect of the triterpenic fraction in L. (L.) amazonensis-infected BALB/c mice. Oleanolic- and ursolic acid-containing fraction was extracted from B. uncinella leaves using organic solvents and chromatographic procedures. L. (L.) amazonensis-infected BALB/c mice were treated intraperitoneally with triterpenic fraction during five consecutive days with 1.0 and 5.0 mg/kg of triterpenic fraction, or with 10.0 mg/kg of amphotericin B drug. Groups of mice treated with the triterpenic fraction, presented with decreased lesion size and low parasitism of the skin-both of which were associated with high amounts of interleukin-12 and interferon gamma. The curative effect of this fraction was similar to amphotericin B-treated mice; however, the final dose, required to eliminate amastigotes, was lesser than amphotericin B. Moreover, triterpenic fraction did not cause microscopic alterations in liver, spleen, heart, lung, and kidney of experimental groups. This work suggests that this fraction possesses compounds that are characterized by leishmanicidal and immunomodulatory activities. From this perspective, the triterpenic fraction can be explored as a new therapeutic agent for use against American Tegumentar Leishmaniasis.

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

“…In this regard, Yamamoto and collaborators (Yamamoto et al., 2014) showed that UA treatment of L. (L.) amazonensis- infected BALB/c mice decreased skin parasitism, which was associated with the preservation of the epidermis and dermis as a possible consequence of IFN-γ production. Other studies showed that the astrakurkurone triterpene from the mushroom Astraeus hygrometricus was able to restrain parasitism in a murine model of VL, and this therapeutic action was associated with the upregulation of IFN-γ and IL-17 cytokines (Chen et al., 2011).…”

“…Additionally, an oleanane triterpenoid derivative (maesabalide III) isolated from Maesa balansae showed in vivo activity against L. donovani following administration of a single subcutaneous dose on either day 1 (prophylactic treatment) or day 28 (curative treatment) after infection (Maes et al., 2004). These data suggest that in addition to their therapeutic effects, some terpenes can also exert modulatory immune effects on animals (Yamamoto et al., 2014, Mallick et al., 2016). …”

“…(Gnoatto et al., 2008, Bero et al., 2011, Begum et al., 2014). Recently, it was demonstrated that ursolic acid (UA) displayed activity against promastigote and amastigote forms of L. (L.) amazonensis , L. (V.) braziliensis , L. (L.) chagasi , and L. (L.) major (Passero et al., 2011, Begum et al., 2014, Yamamoto et al., 2014, Yamamoto et al., 2015), suggesting that UA presents multispectral action. In spite of that, few works have performed in vivo studies in order to evaluate the therapeutic potential of this triterpene and, more importantly, up to now there has not been any report analyzing the therapeutic action of this compound on VL, one of the most important medical conditions caused by Leishmania parasites.…”

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis

“…Triterpenoids are polycyclic compounds derived from the linear hydrocarbon squalene and comprise one of the most promising groups of phytochemicals due to its multifunctionality in the treatment of a broad range of diseases [16][17][18][19][20][21]. For instance, oleanolic acid administered at low doses has hepatoprotective properties, whereas high doses can result in cholestasis and hepatotoxicity [22].…”

Comparative analysis of essential oils of Baccharis L.: a review

“…There are several reports about the biological activity of essential oils from Baccharis as fungicide, anti-bactericidal (GIANELLO et al, 2000;COBOS et al, 2001;DEMO et al, 2005), antiulcerogenic (KLOPELL et al, 2007) and insect repellent (ABAD, BERMEJO, 2007;GARCIA et al, 2005). A research showed that the triterpenes from Baccharis species can be explored as a new therapeutic agent for use against American Tegumentar Leishmaniasis (YAMAMOTO et al, 2014). Schistosomicidal activity was demonstrated for essential oil of B. trimera (Less.)…”