Antiparasitic activity of piplartine (piperlongumine) in a mouse model of schistosomiasis

Mengarda, Ana C.; Mendonça, Poliana S.; Morais, Cristiane S.; Cogo, Ramon M.; Mazloum, Susana F.; Salvadori, M. C.; Teixeira, F. S.; Morais, Thiago R.; Antar, Guilherme Medeiros; Lago, João Henrique G.; Moraes, Josué de

doi:10.1016/j.actatropica.2020.105350

Cited by 41 publications

(38 citation statements)

References 23 publications

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“…We found that treatment with any of the three cardiovascular drugs significantly damaged the worm’s tegument, usually with disintegration of tubercles. These morphological alterations were similar to those reported in studies with other compounds with anthelmintic properties [ 21 , 22 ]. Taken together, the in vitro schistosomicidal activities of amiodarone, telmisartan, and propafenone are in alignment with alterations in the tegumental surfaces of S. mansoni .…”

Section: Discussionsupporting

confidence: 88%

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

et al. 2021

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The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

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Section: Discussionsupporting

confidence: 88%

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

et al. 2021

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“…The oogram consists of one of the most relevant parameters to demonstrate the efficacy of a schistosomicidal compound [8,23–25] . Additionally, the main lesions caused by S. mansoni to the organism are due to the presence of eggs in the tissues of the host, triggering inflammatory reactions and the formation of granulomas [5,8,23–25] .…”

Section: Resultsmentioning

confidence: 99%

“…The life cycle of S. mansoni (BH strain from Adolf Lutz Institute, Brazil) is maintained by passage through snails ( Biomphalaria glabrata ), as the intermediate host, and Swiss female mice ( Mus musculus ) (Anilab, São Paulo, Brazil) as definitive host, as previously described [21,23–25] . Detailed methods for mollusk and mouse infections were previously described [46] .…”

Section: Methodsmentioning

confidence: 99%

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Carvalho

Silva

Souza

et al. 2021

Chemistry & Biodiversity

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Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three‐dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.

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“…Piplartine is one of the main bioactive components found in Piper longum L. Recent studies indicated that piplartine has anti-cancer activities in several types of cancers, including glioblastoma [ 17 ], colon cancer [ 26 ], skin cancer [ 27 ], leukemia [ 28 ], hepatocellular carcinoma [ 29 ]. In addition, piplartine also exhibits antiparasitic activity [ 30 , 31 , 32 , 33 ]; however, the effect of piplartine on immunoregulation has not been well investigated.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

et al. 2021

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Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.

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Antiparasitic activity of piplartine (piperlongumine) in a mouse model of schistosomiasis

Cited by 41 publications

References 23 publications

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation

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