Mode of action of a formulation containing hydrazones and saponins against leishmania spp. Role in mitochondria, proteases and reinfection process

Upegui-Zapata, Yulieth Alexandra; Echeverri, Fernándo; Quiñones, Winston; Torres, Fernando; Nacher, Montserrat; Rivas, Liliana A.; Meira, Camila dos Santos; Gedamu, Lashitew; Escobar, Gustavo; Archbold, Rosendo; Vélez, Iván Darío; Robledo, Sara M.

doi:10.1016/j.ijpddr.2020.06.004

Cited by 12 publications

(11 citation statements)

References 44 publications

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“…Cells were incubated at 37 °C, 5% CO 2 for 72 h; then, the effect of each product on the viability of cells was determined by incubating exposed and unexposed cells for 3 h with 10.0 μL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The MTT was reduced by succinate mitochondrial dehydrogenase to purple formazan that was then solubilized with 100.0 μL/well isopropanol 50% and SDS 10%, and its concentration was determined by optical density at 570 nm in a spectrophotometer (model 680 Bio-Rad microplate CA, USA) [ 20 , 21 , 22 ]. The results represent the means ± SEM from 2 experiments performed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

et al. 2023

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Malachra alceifolia Jacq. (family Malvaceae), known as “malva,” is a medicinal plant used as a traditional therapy in many regions of America, Africa and Asia. Traditionally, this plant is used in the form of extracts, powder and paste by populations for treating fever, stomachache, inflammation, and parasites. However, the ethnopharmacological validation of M. alceifolia has been scarcely researched. This study showed that the chloroform fraction (MA-IC) and subfraction (MA-24F) of the leaves of M. alceifolia exhibited a potential antileishmanial activity against axenic amastigotes of Leishmania mexicana pifanoi (MHOM/VE/60/Ltrod) and had high and moderate cytotoxic effects on the viability and morphology of macrophages RAW 264.7. This study reports, for the first time, possible terpenoid metabolites and derivatives present in M. alceifolia with activity against some biosynthetic pathways in L. mexicana amastigotes. The compounds from the subfractions MA-24F were highly active and were analyzed by gas chromatography-mass spectrometry (GC-MS) and by a molecular docking study in L. mexicana target protein. This study demonstrates the potential modes of interaction and the theoretical affinity energy of the metabolites episwertenol, α-amyrin and methyl commate A, which are present in the active fraction MA-24F, at allosteric sites of the pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase, aldolase, phosphoglucose isomerase, transketolase, arginase and cysteine peptidases A, target proteins in some vital biosynthetic pathways were responsible for the survival of L. mexicana. Some phytoconstituents of M. alceifolia can be used for the search for potential new drugs and molecular targets for treating leishmaniases and infectious diseases. Furthermore, contributions to research and the validation and conservation of traditional knowledge of medicinal plants are needed globally.

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Section: Methodsmentioning

confidence: 99%

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

et al. 2023

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“…The cytotoxicity of the compounds was evaluated according to the viability of the human promonocytic cell line U-937 (ATCC Gaithersburg, MD, United States), as described elsewhere ( Upegui et al, 2020 ). Briefly, cells were cultured at standard conditions in RPMI-1640 medium enriched with 10% inactivated fetal bovine serum (FBS) and 1% penicillin–streptomycin solution.…”

Section: Methodsmentioning

confidence: 99%

“…Nonspecific absorbance was corrected by subtracting the absorbance (OD) of the blank (RPMI-1640 plus 0.2% DMSO). Assays were conducted in duplicate, with each concentration in triplicate ( Upegui et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Exploring Antiparasitic Molecule Sources from Timber by-Product Industries—Leishmanicidal and Trypanocidal Compounds from Clathrotropis brunnea Amshoff

et al. 2020

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Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 μg/ml (17.40 μM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 μg/ml (115.36 μM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 μg/ml (50.39 μM), as well as for T. cruzi, with an EC50 of 18.2 μg/ml (67.38 μM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84–87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.

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“…Because of variable response to therapy and frequency of relapses, more effective, safer, and inexpensive treatments are needed. The hederagenin glucoside saponins (SS) and chromane hydrazone (TC2) combined in a 1 : 1 ratio have high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage 1 . In this work, we developed an ointment formulation containing 2% TC2 and 2% SS (w/w) and determined the skin permeation and the absorption but also the acute dermal toxicity by in vitro and in vivo assays.…”

Section: Financingmentioning

confidence: 99%

Clinical validation of the utility of triterpene saponins from Sapindus saponaria and chroman hydrazone for topical treatment of cutaneous leishmaniasis

Robledo¹,

Piragauta²,

Higuita-Castro³

et al. 2022

Planta Medica

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Mode of action of a formulation containing hydrazones and saponins against leishmania spp. Role in mitochondria, proteases and reinfection process

Cited by 12 publications

References 44 publications

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

Antileishmanial Activity and In Silico Molecular Docking Studies of Malachra alceifolia Jacq. Fractions against Leishmania mexicana Amastigotes

Exploring Antiparasitic Molecule Sources from Timber by-Product Industries—Leishmanicidal and Trypanocidal Compounds from Clathrotropis brunnea Amshoff

Clinical validation of the utility of triterpene saponins from Sapindus saponaria and chroman hydrazone for topical treatment of cutaneous leishmaniasis

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