In vitro activity of hypnophilin from Lentinus strigosus: a potential prototype for Chagas disease and leishmaniasis chemotherapy

Souza-Fagundes, Elaine M.; Cota, Betânia Barros; Rosa, Luiz Henrique; Romanha, Álvaro J.; Corrêa-Oliveira, Rodrigo; Rosa, Carlos A.; Zani, Carlos L.; Teixeira-Carvalho, A.; Martins‐Filho, Olindo Assis

doi:10.1590/s0100-879x2010007500108

Cited by 18 publications

(15 citation statements)

References 20 publications

(24 reference statements)

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“…Terpenoids isolated from Lentinus strigosus and lanostane-type triterpenes isolated from Astraeus hygrometricus are some examples of compounds with promising activity against protozoan parasites such as T. cruzi and Leishmania [9, 24, 27]. …”

Section: Discussionmentioning

confidence: 99%

“…Considering that natural products have been providing interesting scaffolds for protozoan diseases, herein we investigated the potential of basidiomycetes, a rich source for antimicrobial compounds. For example, hypnofylline and panepoxidone isolated from the basidiomycete Lentinus strigosus and an ergosterol peroxide isolated from Pleurotus ostreatus have demonstrated anti- T. cruzi activities [9, 10]. Considering the genus Pleurotus , a number of secondary metabolites have been isolated with different biological properties, such as antitumor, antileishmanial, antimicrobial, anti-inflammatory and antitrypanosomal activities among others [10–14].…”

Section: Introductionmentioning

confidence: 99%

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Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

Alexandre

Lima

Galuppo

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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BackgroundMajor drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom Pleurotus salmoneostramineus in the search for potential antiparasitic compounds.MethodsFruit bodies of the basidiomycete Pleurotus salmoneostramineus were triturated and submitted to organic solvent extraction. After liquid-liquid partition of the crude extract, three fractions were obtained and the bioguided fractionation study was conducted to isolate the active metabolites. The elucidation of the chemical structure was performed using GC-MS and NMR techniques. The biological assays for antiparasitic activity were carried out using trypomastigotes of Trypanosoma cruzi and murine macrophages for mammalian cytotoxicity. The mechanism of action of the isolated compound used different fluorescent probes to evaluate the plasma membrane permeability, the potential of the mitochondrial membrane and the intracellular levels of reactive oxygen species (ROS).ResultsThe most abundant fraction showing the antiparasitic activity was isolated and chemically elucidated, confirming the presence of ergosterol. It showed anti-Trypanosoma cruzi activity against trypomastigotes, with an IC50 value of 51.3 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/mL. The mechanism of action of ergosterol in Trypanosoma cruzi trypomastigotes resulted in permeabilization of the plasma membrane, as well as depolarization of mitochondrial membrane potential, leading to parasite death. Nevertheless, no increase in ROS levels could be observed, suggesting damages to plasma membrane rather than an induction of oxidative stress in the parasite.ConclusionsThe selection of naturally antiparasitic secondary metabolites in basidiomycetes, such as ergosterol, may provide potential scaffolds for drug design studies against neglected diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s40409-017-0120-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

Alexandre

Lima

Galuppo

et al. 2017

J Venom Anim Toxins Incl Trop Dis

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“…To date, a very limited approach has been made to establish the mushrooms or mushroom-derived metabolites as therapeutic or immunostimulatory agents against Leishmania infection. As few as only seven reports, including three from our group, have been documented up to 2015 regarding the antileishmanial effect of extracts or active constituents of wild mushrooms (10)(11)(12)(13)(14)(15)(16). The first breakthrough was made by Jin and Zjawiony in 2006, when they isolated a novel compound, 5-heptadeca-8=Z,11=Z,16-trienylresorcinol, from a polypore mushroom, Merulius incarnatus Schweinitz 1822 (Corticiaceae), which inhibited the Leishmania growth in vitro (50% inhibitory concentration [IC 50 ] of 3.6 g/ml) with no toxicity on Vero cells up to 25 g/ml (10).…”

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confidence: 99%

Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9

Mallick

Dutta

Chaudhuri

et al. 2016

Antimicrob Agents Chemother

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eIn our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroom Astraeus hygrometricus (Pers.) Morgan, induced reactive oxygen species, leading to apoptosis in Leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 g/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity in vitro and in vivo. Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by in vitro assay in the presence of a TLR9 agonist and antagonist and by in silico modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of L. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by in silico evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden in vivo by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance in vitro and in vivo.

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“…There are just few studies describing the antiprotozoal activity of natural products against amastigote form of T. cruzi and most of those investigations have been conducted under in vitro conditions [20–22]. In the performed bioassays, the in vivo antiprotozoal activity of chloroform extract of C. papaya seeds during the subacute and chronic phase of Chagas' disease was evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…This fraction was reported as not cytotoxic, mutagenic, or genotoxic [20]. Another compound with antiprotozoal activity against the amastigote stage in vitro is the terpenoid hypnophilin, purified from Lentinus strigosus , which demonstrated a significant inhibitory activity over T. cruzi tripanotion reductase [22]. …”

Section: Resultsmentioning

confidence: 99%

In VivoAntiprotozoal Activity of the Chloroform Extract fromCarica papayaSeeds against Amastigote Stage ofTrypanosoma cruziduring Indeterminate and Chronic Phase of Infection

Jiménez‐Coello

Acosta-Viana

Ortega‐Pacheco

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection.

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In vitro activity of hypnophilin from Lentinus strigosus: a potential prototype for Chagas disease and leishmaniasis chemotherapy

Cited by 18 publications

References 20 publications

Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9

In VivoAntiprotozoal Activity of the Chloroform Extract fromCarica papayaSeeds against Amastigote Stage ofTrypanosoma cruziduring Indeterminate and Chronic Phase of Infection

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