Pharmacological Potential of Selected Natural Compounds in the Control of Parasitic Diseases by Gabriela Hrckova & Samuel Velebny

Author:Gabriela Hrckova & Samuel Velebny
Language: eng
Format: epub
Publisher: Springer Vienna, Vienna

Proteosynthesis and proteolysis in the worms are highly regulated and inter-connected processes and genistein was able to induce the alterations in the free amino acid pool and ammonia levels in the fluke Fasciolipsis buski (Kar et al. 2004). Valine was found to be the most elevated amino acid as well as the levels of GABA and citrulline, which could be associated with the elevated activity of nNOS. Ammonia in the tissue homogenates as well as in incubation medium increased (66.4 %) compared to the controls. These data might indicate that genistein could be an effective compound in the therapy of gastrointestinal cestode and trematode infections, but it is necessary to determine the effective concentration and treatment schedule on animal models. There is a risk that the higher doses might lead to the uncontrolled stimulation of selected immune mechanisms, which are known to be the targets of genistein in mammals. It was shown that genistein, kaempferol, and quercetin can inhibit activation of the signal transducer and activator of transcription 1 (STAT-1), important transcription factor for iNOS and NO production in activated macrophages (Hämäläinen et al. 2007). The estrogen-like activity of genistein is a major concern during long-term chemotherapy as it binds to estrogen receptors and can induce estrogenic effects. Prolonged treatment with current anthelmintics is required to inhibit growth of parasitic cysts of E. multilocularis. It was shown that genistein exhibited significant metacestodicidal activity against E. multilocularis in vitro as well as against E. granulosus metacestodes and protoscoleces (Nagulesvaran et al. 2006). The native compound and synthetic derivatives of genistein, Rm 6423, and Rm 6426 induced truncation of microtriches, nuclear pyknosis, and vesiculations of protoscoleces. In addition, Rm 6423 specifically induced dramatic breakdown of the structural integrity of the germinal layer in metacsetode cysts and a decrease of activity of metalloproteases, which allows the growth of cysts in the host tissues. Inter-individual, species and sex differences in gastrointestinal metabolism of this phytoestrogen may be critical factors in determining the efficacy of these various compounds in vivo.

There are a few studies, in which nematocidal activity of other plant-derived flavonoids was demonstrated in vitro and in vivo. The antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite B. malayi was evaluated using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (MTT-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections) (Lakshmi et al. 2010). All six flavonoids showed antifilarial activity in vitro, which can be classed in a decreasing order: naringenin > flavone = hesperetin > rutin > naringin > chrysin. IC50 of naringenin was 2.5 μg/ml and adulticidal effect was seen at 125 μg/ml. In jirds, naringenin and flavone killed or sterilized adult worms at dose of 50 mg/kg, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. All the flavonoids tested were well tolerated in both the animal models and there were no signs of behavioral or other changes that can be related to flavonoid treatment in the animals.

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