In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis

Abstract

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue

“…Antimalarial hit compounds against the chloroquine resistant strains included compounds 8 (IC 50 : 0.95 μg/ml; Azebaze et al, ); 34 (IC 50 : 2.94 μM; Ganesh et al, ); 62 (IC 50 : 1.7 μM); 63 (IC 50 : 2.1 μM; De Monbrison et al, ); and 77 (IC 50 : 0.08 μg/ml; SI: 375 MRC‐5 cells; Konziase, ). In cutaneous leishmaniasis, the hit compounds included compounds 30 (IC 50 : 4.3 μM; SI: 18.3, macrophage cells; Fonseca‐Silva et al, ); 34 (IC 50 : 0.7 μM; SI: 10, macrophage cells; Montrieux et al, ); 92 (IC 50 : 0.2 μM; SI: 22, J774.A1 cells; Rizk et al, ); 95 (IC 50 : 8.1 μM; SI: 24.6, macrophage cells); and 96 (IC 50 : 3.2 μM; SI: 39.6, macrophage cells; Lage et al, ). Some other antileishmanial compounds with low IC 50 , that is, compounds 7 (IC 50 : 0.1390 μM); 103 (IC 50 : 0.0513 μM); and 104 (IC 50 : 0.0446 μM; Gontijo et al, ), were also nominated as hit compounds.…”

“…Among six flavonoids ( 27 , 87 – 91 ) isolated from Renealmia thyrsoidea and evaluated for antileishmanial activity against L. amazonensis , 90 showed moderate inhibitory effects (IC 50 : 23.1 μM), whereas amphotericin afforded an IC 50 value of 0.15 μM (Cabanillas et al, ). Amentoflavone ( 92 ) and robustaflavone ( 93 ) (isolates of Selaginella sellowii ) were effective against L. amazonensis (incubation time: 72 hr), with IC 50 values of 0.1 μg/ml (SI: 22 and 30 for J774.A1 and NIH/3 T3 cells, respectively) and 2.8 μg/ml (SI: 9.1; J774.A1 cells), respectively, compared with amphotericin B (0.03 μg/ml; Rizk et al, ). Sandjo et al () reported the antileishmanial activity of 6,8‐diprenyleriodictyol ( 94 ; IC 50 : 12.38 μg/ml; albeit not selective vs. THP‐1 cells) against intracellular amastigotes of L. amazonensis , whereas amphotericin B displayed IC 50 value 0.07 μM.…”

In Vivo and in Vitro Antileishmanial Effects of Methanolic Extract From Bark of Bursera Aptera

“…Our findings show that the size of the lesion and the parasitic load is smaller in MEBA-treated mice than untreated mice. It has been reported that flavonoids isolated from Selaginella sellowi, amentoflavone (0.1 μg/mL) and robustoflavone (2.8 μg/mL), have anti-leishmanial activity on amastigotes of L. amazonensis (Rizk et al, 2014). In addition, previous reports demonstrated the antileishmanial activity of quercetin, quercetrin and isoquercetrin, as they inhibit recombinant arginase from L. amazonensis at an LC 50 of 4.3, 10.0 and 3.8 μM, respectively (Da Silva et al, 2012).…”

A Nitrile Glucoside and Biflavones from the Leaves of Campylospermum excavatum (Ochnaceae)

“…It should be noticed that 3 was reported to be active against the intracellular amastigotes (peritoneal macrophages from BALB/c mice were used) of other species (L. amazonensis). [18] This fact could be explained again, by the strain specific expression of ABC transporters, known to occur in Leishmania. [28]…”