Therapeutic effect of oral quercetin in hamsters infected with Leishmania Viannia braziliensis

Abstract

Leishmaniasis is a parasitic disease caused by several species of intracellular protozoa of the genus Leishmania that present manifestations ranging from cutaneous ulcers to the fatal visceral form. Leishmania Viannia braziliensis is an important species associated with American tegumentary leishmaniasis and the main agent in Brazil, with variable sensitivity to available drugs. The search for new therapeutic alternatives to treat leishmaniasis is an urgent need, especially for endemic countries. Not only is quercetin well known for its antioxidant activity in radical scavenging but also several other biological effects are described, including anti-inflammatory, antimicrobial, and pro-oxidant activities. This study aimed to investigate the flavonoid quercetin’s therapeutic potential in L. (V.) braziliensis infection. Quercetin showed antiamastigote (IC50 of 21 ± 2.5 µM) and antipromastigote (25 ± 0.7 µM) activities and a selectivity index of 22. The treatment of uninfected or L. (V.) braziliensis–infected macrophages with quercetin increased reactive oxygen species (ROS)/H202 generation without altering Nitric Oxide (NO) production. Oral treatment with quercetin of infected hamsters, starting at 1 week of infection for 8 weeks, reduced the lesion thickness (p > 0.01) and parasite load (p > 0.001). The results of this study suggest that the antiamastigote activity of the flavonoid quercetin in vitro is associated, at least in part, with the modulation of ROS production by macrophages. The efficacy of oral quercetin treatment in hamsters infected with L. (V.) braziliensis was presented for the first time and shows its promising therapeutic potential.

Piperine, quercetin, and curcumin identified as promising natural products for topical treatment of cutaneous leishmaniasis

“…They suggested that QUE’s antileishmanial effects on amastigotes involve activating Nrf2/HO-1, followed by modulating labile iron stores, resulting in depleted iron for the replication and survival of L. braziliensis . Recently, Santos et al assessed the oral administration of QUE for the first time in hamsters infected with L. braziliensis , unveiling antiamastigote activity (EC 50 of 21 ± 2.5 µM) (Dos Santos et al 2022 ). A substantial decrease in macrophage viability was observed only at concentrations exceeding 640 µM, with an estimated EC 50 of 478 ± 89 µM and a SI of 22, mirroring our study’s results.…”

“…These in vivo findings reaffirm the therapeutic potential of QUE for CL and corroborate previous studies in different CL and VL models. In Santos et al’s study, it was shown that administering oral QUE (20 mg/kg; five times a week) to hamsters infected with L. braziliensis , starting 7 days after infection for 8 weeks, effectively controlled the lesion size and reduced the parasite load in both the lesion and the draining lymph node (Dos Santos et al 2022 ). In another study, histopathological analysis revealed a reduction in inflammatory cell count, an increase in fibroblasts, and enhanced collagen deposition in tissue sections from mice infected with L. major and subjected to oral QUE treatment at a dosage of 50 mg/kg for 28 consecutive days (Almadani et al 2021 ).…”

Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues

“…A recent study demonstrated that Que had a dose-dependent cytotoxicity against both L. braziliensis promastigotes and amastigotes [ 28 ]. However, several studies have shown that Que had lower antileishmanial activity than amphotericin B [ 24 , 27 ], SSG [ 25 ], and miltefosine [ 28 ]. Compared to mammalian cell lines, Leishmania promastigotes are more susceptible to the inhibitory effects of Que ( Table 2 ).…”

“…In a recent study, treatment of L. braziliensis -infected hamsters with oral Que (20 mg/kg, five times a week), for eight weeks starting from the first week of infection, significantly decreased lesion thickness and parasite load [ 28 ]. However, oral Que exhibited lower in vivo efficacy compared to intraperitoneal Glucantime® (80 mg/kg, three times a week).…”

“…A recent study demonstrated that Que had a dose-dependent cytotoxicity against both L. braziliensis promastigotes and amastigotes [28]. However, several studies have shown that Que had lower antileishmanial activity than amphotericin B [24,27], SSG [25], and miltefosine [28].…”