Toxic, cytotoxic and genotoxic effect of plumbagin in the developmental stages of <i>Biomphalaria glabrata</i> (Say, 1818‐intermediate host) and cercaricidal activity against the infectious agent of schistosomiasis mansoni

França, Wilza Wanessa Melo; Silva, Adriana Maria da; Diniz, Emily Gabriele Marques; Silva, Hianna Arely Milca Fagundes; Pereira, Dewson Rocha; Melo, Ana Maria Mendonça de Albuquerque; Coelho, Luana Cassandra Breitenbach Barroso; Albuquerque, Mônica Camelo Pessôa de Azevedo; Araújo, Hallysson Douglas Andrade de; Aires, André de Lima

doi:10.1002/ps.7136

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…Phytochemical studies of P. auriculata have resulted in the isolation of sitosterol, stigmasterol, 3- O -glycosylsitosterol, palmitic acid, plumbagic acid, epi-isoshinanolone, luteolin, 5-methoxyluteolin and plumbagin. The bioactive naphthoquinone plumbagin (C 11 H 8 O 3 ) has an antitumor effect [ 28 , 29 , 30 ] and is active against multidrug-resistant clinical isolates of bacteria [ 31 , 32 ], besides presenting molluscicidal and antischistosomiasis [ 33 ], antimalarial [ 34 ] and antileishmanial [ 35 ] properties.…”

Section: Introductionmentioning

confidence: 99%

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

et al. 2023

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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.

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Section: Introductionmentioning

confidence: 99%

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

et al. 2023

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“…These are known to present biological properties such as antibacterial [ 33 , 34 ], anticancer [ 35 ], antifungal [ 34 ], anti-inflammatory [ 36 ], and cardioprotective, hepatoprotective, and neuroprotective [ 37 ]. In addition, these compounds have potential in controlling pests and vectors [ 38 , 39 ], as a larvicide, and a mosquitocide [ 40 ]. Naphthoquinones have been highlighted as a promising antiparasitic agent against Leishmania spp.…”

Section: Introductionmentioning

confidence: 99%

Plumbagin: A Promising In Vivo Antiparasitic Candidate against Schistosoma mansoni and In Silico Pharmacokinetic Properties (ADMET)

Silva,

França,

Santos

et al. 2023

Biomedicines

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Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus Schistosoma spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of Schistosoma-resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus Plumbago, has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo schistosomicidal potential of PLUM against Schistosoma mansoni and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato–Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against S. mansoni, acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET.

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Bisphenol A effects on the host Biomphalaria alexandrina and its parasite Schistosoma mansoni

Habib,

Mohamed,

Nassar

et al. 2023

Environ Sci Pollut Res

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Toxic, cytotoxic and genotoxic effect of plumbagin in the developmental stages of Biomphalaria glabrata (Say, 1818‐intermediate host) and cercaricidal activity against the infectious agent of schistosomiasis mansoni

Cited by 4 publications

References 51 publications

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

Plumbagin: A Promising In Vivo Antiparasitic Candidate against Schistosoma mansoni and In Silico Pharmacokinetic Properties (ADMET)

Bisphenol A effects on the host Biomphalaria alexandrina and its parasite Schistosoma mansoni

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