In VitroSchistosomicidal Activity of Some Brazilian Cerrado Species and Their Isolated Compounds

Abstract

Miconia langsdorffii Cogn. (Melastomataceae), Roupala montana Aubl. (Proteaceae), Struthanthus syringifolius (Mart.) (Loranthaceae), and Schefflera vinosa (Cham. & Schltdl.) Frodin (Araliaceae) are plant species from the Brazilian Cerrado whose schistosomicidal potential has not yet been described. The crude extracts, fractions, the triterpenes betulin, oleanolic acid, ursolic acid and the flavonoids quercetin 3-O-β-D-rhamnoside, quercetin 3-O-β-D-glucoside, quercetin 3-O-β-D-glucopyranosyl-(1-2)-α-L-rhamnopyranoside and isorhamnetin 3-O-β-D-glucopyranosyl-(1-2)-α-L-rhamnopyranoside were evaluated in vitro against Schistosoma mansoni adult worms and the bioactive n-hexane fractions of the mentioned species were also analyzed by GC-MS. Betulin was able to cause worm death percentage values of 25% after 120 h (at 100 μM), and 25% and 50% after 24 and 120 h (at 200 μM), respectively; besides the flavonoid quercetin 3-O-β-D-rhamnoside promoted 25% of death of the parasites at 100 μM. Farther the flavonoids quercetin 3-O-β-D-glucoside and quercetin 3-O-β-D-rhamnoside at 100 μM exhibited significantly reduction in motor activity, 75% and 87.5%, respectively. Biological results indicated that crude extracts of R. montana, S. vinosa, and M. langsdorffii and some n-hexane and EtOAc fractions of this species were able to induce worm death to some extent. The results suggest that lupane-type triterpenes and flavonoid monoglycosides should be considered for further antiparasites studies.

Natural Products with Antischistosomal Activity

“…The terpenes with antischistosomal activity are: rotundifolone [66], (+)-limonene epoxide [56], and carvacryl acetate, a derivative of carvacrol (monoterpenes) [39]; artemisinin and its derivatives [30,31], nerolidol [59], and budlein-A and its derivatives [38] (sesquiterpenes); phytol [60] (diterpene), betulin [37] and its triphenylphosphonium derivatives [69], balsaminol F, karavilagenin C [36] (triterpenes) (Figure 1). Importantly, among the group of terpenes, in vitro and in vivo antischistosomal properties have been described only for artemisinin and its derivatives, phytol and triphenylphosphonium derivatives, whereas it was reported in vitro schitosomicidal activity for other terpenes (Table 1).…”

“…A recent study has showed that betulin isolated from Schefflera vinosa (Araliaceae), a plant from the Brazilian Savannah, was effective in vitro against S. mansoni adult worms at a concentration of 100-200 μM [37]. More recently, Spivak et al [69] have synthesized triphenylphosphonium derivatives of betulin and betulinic acid and results showed in vitro antischistosomal of activity against newly transformed schistosomula and adult worms of S. mansoni at low micromolar concentrations (<10 μM and <2 μM, respectively).…”

“…The antischistosomal activity of betulin and betulinic acid phosphonium derivatives might be explained due to their influence on the cholinergic nervous system of S. mansoni. Moreover, the specific structure of the body surface of trematodes consists of a tegument with a high concentration of mitochondria on the surface, making the body surface of this parasite vulnerable for potential mitochondria-targeting compounds [37]. Nevertheless, the exact mechanism of action remains to be elucidated.…”

“…Quinones, flavonoids, neolignans and other phenolic derivatives have anthelmintic activities against schistosomes. The phenolic compounds with antischistosomal activity are: plumbagin [64,65], β-lapachone [53,54], quercetin 3-O-β-d-glucoside, quercetin 3-O-β-drhamnoside [37], kaempferol [52], sativan [67], hesperidin [50,51], (±)-licarin A and its enantiomer [55], curcumin [40][41][42][43][44] and some phloroglucinol derivatives such as aspidin, flavaspidic acid, methylene-bis-aspidinol and desaspidin (Figure 3) [35].…”

In Vitro Antischistosomal Activity and Cytotoxicity of 5-Methoxylated Flavones fom Vochysia divergens, a Flood-Adapted Species from Brazilian Pantanal

“…As part of our advancing investigation on the schistosomicidal activity of Brazilian species from "Cerrado" and "Pantanal" [10][11][12], the present work reports on the in vitro schistosomicidal activity of the ethanolic extract and three isolated 5-methoxy-flavones from V. divergens leaves.…”