Gallic and ellagic acids: two natural immunomodulator compounds solve infection of macrophages by Leishmania major

Abstract

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC) values 16.4 and 9.8 μg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC values 126.6 and 23.8 μg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC values 5.0 and 0.9 μg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.

Impact of Gallic Acid on Gut Health: Focus on the Gut Microbiome, Immune Response, and Mechanisms of Action

“…GA could improve immunomodulatory activity by increasing of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium ( ) levels in macrophages ( 138 ) and downregulate the MAPK-linked phagocytic signaling pathway in mouse murine macrophages ( 139 ). The efflux transporters P-glycoprotein and multidrug resistance proteins might participate in the transport of GA, and paracellular transport appeared to be the major limiting factor for the uptake of GA in Caco-2 cell monolayers ( 140 ).…”

Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo

“…The values are the means of experiments in triplicate c Ratio of the EC 50 of cell lines to the IC 50 of each species. High numbers are favorable d [7] e [14] Abbreviations : EA, ellagic acid; β-CD EA, β-cyclodextrin ellagic acid; APSP EA, antisolvent precipitation with a syringe pump prepared ellagic acid; MDBK, Madin–Darby bovine kidney; NIH/3T3, mouse embryonic fibroblast; HFF, human foreskin fibroblast…”

“…EA and its microspheres (β-CD EA and APSP EA) were effective against Babesia and Theileria parasites in vitro , while APSP EA showed the lowest IC 50 values. Previous reports documented EA’s strong inhibition of the growth of many protozoan parasites, including Plasmodium , Trypanosoma and Leishmania , by different action mechanisms [12–14]. However, the mode of action is yet to be understood comprehensively in comparison to the existing data.…”

“…Aminu et al [13] reported the in vitro , in silico antisialidase activities and the in vivo antitrypanosomal potentials of EA. Moreover, Alves et al [14] revealed the antileishmanial activity of EA on promastigote forms of Leishmania major .…”

In Vitro Effect of Methanolic Extract of Quercus infectoria Galls on Promastigotes and Amastigotes of Leishmania major (MRHO/IR/75/ER)

“…Different concentrations of the extract and Glucantime significantly affected the survival rate of amastigotes in microphages compared with the control ( Table 1). growth inhibitors of promastigote of L. major (19).…”