Natural compounds based chemotherapeutic against Chagas disease and leishmaniasis: mitochondrion as a strategic target

Lazarin-Bidóia, Danielle; Garcia, Francielle P.; Ueda-Nakamura, Tânia; Silva, Sueli de Oliveira; Nakamura, Celso Vataru

doi:10.1590/0074-02760220396

Cited by 8 publications

(4 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the pretreatment with oleoresin and hydroalcoholic extract from C. multijuga suggested that these compounds can directly affect the parasite structure and, consequently, decrease its functional capabilities. A recent study declared that these natural compounds can affect different structures in T. cruzi and Leishmania spp, and it is hypothesized that the mitochondrion is a strategic target to induce parasite death ( Lazarin-Bidóia et al., 2022 ). Also, L. infantum and L. amazonensis promastigotes treated with nanoemulsion from Copaifera presented ultrastructural alterations as oval cell shape and retracted flagella ( De Moraes et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Extracts and purified molecules of various species of the genera Piper , Tanacetum , Porophyllum and Copaifera exhibited interesting antitrypanosomal and antileishmanial activities. These natural compounds affected different structures in the parasites, suggesting that the mitochondria are the strategic target to induce parasite death ( Lazarin-Bidóia et al., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Martínez

Teixeira²,

Souza³

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

The conventional treatment of congenital toxoplasmosis is mainly based on the combination of sulfadiazine and pyrimethamine. However, therapy with these drugs is associated with severe side effects and resistance, requiring the study of new therapeutic strategies. There are currently many studies with natural products, including Copaifera oleoresin, showing actions against some pathogens, as Trypanosoma cruzi and Leishmania. In the present study, we investigated the effects of the leaf hydroalcoholic extract and oleoresin from Copaifera multijuga against Toxoplasma gondii in human villous (BeWo) and extravillous (HTR8/SVneo) trophoblast cells, as well as in human villous explants from third-trimester pregnancy. For this purpose, both cells and villous explants were infected or not with T. gondii, treated with hydroalcoholic extract or oleoresin from C. multijuga and analyzed for toxicity, parasite proliferation, cytokine and ROS production. In parallel, both cells were infected by tachyzoites pretreated with hydroalcoholic extract or oleoresin, and adhesion, invasion and replication of the parasite were observed. Our results showed that the extract and oleoresin did not trigger toxicity in small concentrations and were able to reduce the T. gondii intracellular proliferation in cells previously infected. Also, the hydroalcoholic extract and oleoresin demonstrated an irreversible antiparasitic action in BeWo and HTR8/SVneo cells. Next, adhesion, invasion and replication of T. gondii were dampened when BeWo or HTR8/SVneo cells were infected with pretreated tachyzoites. Finally, infected and treated BeWo cells upregulated IL-6 and downmodulated IL-8, while HTR8/SVneo cells did not change significantly these cytokines when infected and treated. Finally, both the extract and oleoresin reduced the T. gondii proliferation in human explants, and no significant changes were observed in relation to cytokine production. Thus, compounds from C. multijuga presented different antiparasitic activities that were dependent on the experimental model, being the direct action on tachyzoites a common mechanism operating in both cells and villi. Considering all these parameters, the hydroalcoholic extract and oleoresin from C. multijuga can be a target for the establishment of new therapeutic strategy for congenital toxoplasmosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Martínez

Teixeira²,

Souza³

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…This occurs also with neglected tropical diseases, such as Chagas disease [ 1 ]. Therefore, biodiversity, that is mainly strictly related to medicinal plants, has been a source of compounds that could turn into drug candidates [ 98 ]. Searching for a mechanism of RVT action, in 2012, Vera and colleagues [ 99 ] performed docking with arginine kinase, a possible target from T. cruzi , using 24 polyphenolic compounds and 18 arginine analogues downloaded from the ZINC database.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Imperador¹,

Scarim

Bosquesi

et al. 2022

Pharmaceuticals

View full text Add to dashboard Cite

Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage—characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease’s progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease’s severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.

show abstract

“…Many studies with such drugs are in the preclinical phase for trypanosomiasis (using methodologies based on in vitro or animal studies), clinical trials, and described in case reports. Also, synthetic, semi-synthetic [ 93 , 94 , 95 , 96 , 97 ], and natural compounds have been proposed as alternatives for the treatment of these trypanosomiases [ 98 , 99 , 100 , 101 ]. Among these natural compounds with anti-trypanosome activity, AMPs are included [ 16 , 102 , 103 ].…”

Section: Other Therapeutic Alternatives Against Trypanosomiasismentioning

confidence: 99%

Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?

et al. 2023

View full text Add to dashboard Cite

Trypanosomiases are a group of tropical diseases that have devastating health and socio-economic effects worldwide. In humans, these diseases are caused by the pathogenic kinetoplastids Trypanosoma brucei, causing African trypanosomiasis or sleeping sickness, and Trypanosoma cruzi, causing American trypanosomiasis or Chagas disease. Currently, these diseases lack effective treatment. This is attributed to the high toxicity and limited trypanocidal activity of registered drugs, as well as resistance development and difficulties in their administration. All this has prompted the search for new compounds that can serve as the basis for the development of treatment of these diseases. Antimicrobial peptides (AMPs) are small peptides synthesized by both prokaryotes and (unicellular and multicellular) eukaryotes, where they fulfill functions related to competition strategy with other organisms and immune defense. These AMPs can bind and induce perturbation in cell membranes, leading to permeation of molecules, alteration of morphology, disruption of cellular homeostasis, and activation of cell death. These peptides have activity against various pathogenic microorganisms, including parasitic protists. Therefore, they are being considered for new therapeutic strategies to treat some parasitic diseases. In this review, we analyze AMPs as therapeutic alternatives for the treatment of trypanosomiases, emphasizing their possible application as possible candidates for the development of future natural anti-trypanosome drugs.

show abstract

Natural compounds based chemotherapeutic against Chagas disease and leishmaniasis: mitochondrion as a strategic target

Cited by 8 publications

References 53 publications

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Leaf hydroalcoholic extract and oleoresin from Copaifera multijuga control Toxoplasma gondii infection in human trophoblast cells and placental explants from third-trimester pregnancy

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?

Contact Info

Product

Resources

About