Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi
Chagas disease (CD) caused by the protozoan Trypanosoma cruzi affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. Therefore, new therapeutic options are necessary. In this scenario, natural products emerge as promising alternatives to treat CD. In the family Plumbaginaceae, Plumbago sp. exhibits a broad spectrum of biological and pharmacological activities. Thus, our main objective was to evaluate, in vitro and in silico, the biological effect of crude extracts of root and of aerial parts of P. auriculata, as well as its naphthoquinone Plumbagin (Pb) against T. cruzi. The phenotypic assays revealed potent activity of the root extract against different forms (trypomastigote and intracellular forms) and strains (Y and Tulahuen), with a compound concentration that reduced 50% of the number of the parasite (EC50) values ranging from 1.9 to 3.9 µg/mL. In silico analysis showed that Pb is predicted to have good oral absorption and permeability in Caco2 cells, besides excellent probability of absorption by human intestinal cells, without toxic or mutagenic potential effects, not being predicted as a substrate or inhibitor of P-glycoprotein. Pb was as potent as Bz against intracellular forms and displayed a superior trypanosomicidal effect (about 10-fold) in bloodstream forms (EC50 = 0.8 µM) as compared to the reference drug (8.5 µM). The cellular targets of Pb on T. cruzi were evaluated using electron microscopy assays and the findings on bloodstream trypomastigotes showed several cellular insults related to the autophagic process. Regarding toxicity in mammalian cells, the root extracts and the naphthoquinone present a moderate toxic profile on fibroblasts and cardiac cell lines. Then, aiming to reduce host toxicity, the root extract and Pb were tested in combination with Bz, and the data showed additive profiles with the sum of the fractional inhibitory concentration indexes (ΣFICIs) being 1.45 and 0.87, respectively. Thus, our work reveals the promising antiparasitic activity of Plumbago auriculata crude extracts and its purified naphthoquinone Plumbagin against different forms and strains of Trypanosoma cruzi in vitro.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Pharmaceutics - 15(2023), 5 vom: 19. Mai |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Peres, Raiza Brandão [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chagas disease |
|---|
| Anmerkungen: |
Date Revised 29.05.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/pharmaceutics15051535 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35745006X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35745006X | ||
| 003 | DE-627 | ||
| 005 | 20231226072621.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/pharmaceutics15051535 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1191.xml |
| 035 | |a (DE-627)NLM35745006X | ||
| 035 | |a (NLM)37242777 | ||
| 035 | |a (PII)1535 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Peres, Raiza Brandão |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 29.05.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Chagas disease (CD) caused by the protozoan Trypanosoma cruzi affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. Therefore, new therapeutic options are necessary. In this scenario, natural products emerge as promising alternatives to treat CD. In the family Plumbaginaceae, Plumbago sp. exhibits a broad spectrum of biological and pharmacological activities. Thus, our main objective was to evaluate, in vitro and in silico, the biological effect of crude extracts of root and of aerial parts of P. auriculata, as well as its naphthoquinone Plumbagin (Pb) against T. cruzi. The phenotypic assays revealed potent activity of the root extract against different forms (trypomastigote and intracellular forms) and strains (Y and Tulahuen), with a compound concentration that reduced 50% of the number of the parasite (EC50) values ranging from 1.9 to 3.9 µg/mL. In silico analysis showed that Pb is predicted to have good oral absorption and permeability in Caco2 cells, besides excellent probability of absorption by human intestinal cells, without toxic or mutagenic potential effects, not being predicted as a substrate or inhibitor of P-glycoprotein. Pb was as potent as Bz against intracellular forms and displayed a superior trypanosomicidal effect (about 10-fold) in bloodstream forms (EC50 = 0.8 µM) as compared to the reference drug (8.5 µM). The cellular targets of Pb on T. cruzi were evaluated using electron microscopy assays and the findings on bloodstream trypomastigotes showed several cellular insults related to the autophagic process. Regarding toxicity in mammalian cells, the root extracts and the naphthoquinone present a moderate toxic profile on fibroblasts and cardiac cell lines. Then, aiming to reduce host toxicity, the root extract and Pb were tested in combination with Bz, and the data showed additive profiles with the sum of the fractional inhibitory concentration indexes (ΣFICIs) being 1.45 and 0.87, respectively. Thus, our work reveals the promising antiparasitic activity of Plumbago auriculata crude extracts and its purified naphthoquinone Plumbagin against different forms and strains of Trypanosoma cruzi in vitro | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chagas disease | |
| 650 | 4 | |a Plumbagin | |
| 650 | 4 | |a Plumbago auriculata | |
| 650 | 4 | |a drug combination | |
| 650 | 4 | |a in silico ADMET | |
| 650 | 4 | |a naphthoquinone | |
| 650 | 4 | |a natural products | |
| 700 | 1 | |a Batista, Marcos Meuser |e verfasserin |4 aut | |
| 700 | 1 | |a Bérenger, Ana Luíza Rangel |e verfasserin |4 aut | |
| 700 | 1 | |a Camillo, Flávia da Cunha |e verfasserin |4 aut | |
| 700 | 1 | |a Figueiredo, Maria Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a Soeiro, Maria de Nazaré Correia |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmaceutics |d 2010 |g 15(2023), 5 vom: 19. Mai |w (DE-627)NLM204303303 |x 1999-4923 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2023 |g number:5 |g day:19 |g month:05 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/pharmaceutics15051535 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2023 |e 5 |b 19 |c 05 | ||