Commercial drugs containing flavonoids are active in mice with malaria and in vitro against chloroquine-resistant Plasmodium falciparum

Abstract

BACKGROUND The main strategy to control human malaria still relies on specific drug treatment, limited now by Plasmodium falciparum-resistant parasites, including that against artemisinin derivatives. Despite the large number of active compounds described in the literature, few of them reached full development against human malaria. Drug repositioning is a fast and less expensive strategy for antimalarial drug discovery, because these compounds are already approved for human use. OBJECTIVES To identify new antimalarial drugs from compounds commercially available and used for other indications. METHODS Accuvit®, Ginkgo® and Soyfit®, rich in flavonoids, and also the standard flavonoids, hesperidin, quercetin, and genistein were tested against blood cultures of chloroquine-resistant P. falciparum, as well as chloroquine, a reference antimalarial. Inhibition of parasite growth was measured in immunoenzymatic assay with monoclonal anti-P. falciparum antibodies, specific to the histidine-rich protein II. Tests in mice with P. berghei malaria were based on percent of parasitaemia reduction. These compounds were also evaluated for in vitro cytotoxicity. FINDINGS The inhibition of parasite growth in vitro showed that Accuvit® was the most active drug (IC50 5 ± 3.9 μg/mL). Soyfit® was partially active (IC50 13.6 ± 7.7 μg/mL), and Ginkgo® (IC50 38.4 ± 14 μg/mL) was inactive. All such compounds were active in vivo at a dose of 50 mg/kg body weight. Accuvit® and quercetin induced the highest reduction of P. berghei parasitaemia (63% and 53%, respectively) on day 5 after parasite inoculation. As expected, the compounds tested were not toxic. MAIN CONCLUSIONS The antimalarial activity of Accuvit® was not related to flavonoids only, and it possibly results from synergisms with other compounds present in this drug product, such as multivitamins. Multivitamins in Accuvit® may explain its effect against the malaria parasites. This work demonstrated for the first time the activity of these drugs, which are already marketed.

Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria

“…Findings from our in vitro studies showed that quercetin exhibited moderate anti-plasmodial activity with a high selectivity index. This observation that quercetin exhibits in vitro anti-plasmodial activity corroborates previous reports by other investigators [ 28 ]. Another study [ 44 ] showed that aminoalkylated-quercetin analogues exhibited strong anti-malarial activities with IC 50 values within the nanomolar to low micromolar range against P. falciparum W2, D6, and C235.…”

“…There have been various reports on the anti-plasmodial activity of quercetin [ 26 ] and its analogues against clinical isolates of Plasmodium falciparum [ 27 ]. Recently, it was demonstrated that selected existing commercial flavonoids (including quercetin)-containing drugs for other diseases are active in malaria-infected mice and in vitro against chloroquine-resistant P. falciparum [ 28 ]. It was suggested that the anti-oxidant capacity of the tested drugs could be responsible for the reduction of malaria severity.…”

<i>In vitro</i> efficacy of <i>Capparis spinosa</i> extraction against larvae viability of <i>Echinococcus granulosus</i> sensu stricto

“…The ethanolic extract of C. spinosa fruit contains mainly polyphenols and flavonoids. Several studies have reported that polyphenols and flavonoids in natural extracts have significant inhibitory effects on parasitic infection [ 8 , 26 ]. In addition, this phenomenon might also be due to the different active chemical compositions and concentrations of water-soluble and ethanolic extracts, and the choice of solvent can affect the chemical composition and content of each extract.…”

Ethnopharmacology and phytochemistry-based review on the antimalarial potential of Acacia pennata (L.) Willd.

“…23 . The antimalarial activity of flavonoids had been reported by Ichino et al, 24 Khaomek et al 25 and Penna-Coutinho et al 26 Glycosides are bioactive compounds that attaches itself to an aglycone via a glycosidic bond. The glycoside moiety plays a crucial role in altering the pharmacology and pharmacokinetic profiles of the aglycone moiety.…”