A novel Triterpene from
 Astraeus Hygrometricus
 Induces Reactive Oxygen Species Leading to death in
 Leishmania Donovani

Mallick, Suvadip; Dey, Somaditya; Mandal, Supratim; Dutta, Aritri; Mukherjee, Debarati; Biswas, Gunjan; Chatterjee, S.; Mallick, Sourav; Lai, Tapan Kumar; Acharya, Krishnendu; Pal, Chiranjib

doi:10.2217/fmb.14.149

Cited by 41 publications

(31 citation statements)

References 33 publications

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“…In continuation with our line of investigation on antileishmanial leads, we also claimed simultaneously the isolation and structure elucidation of a novel triterpene molecule, astrakurkurone, from an active fraction of A. hygrometricus, with a significant effect against promastigotes (14). We have also reported the involvement of reactive oxygen species (ROS) and mitochondrial dysfunction in astrakurkurone-mediated cell death in promastigotes (16). Astrakurkurone was also found effective against clinically important intracellular amastigotes, with a significantly low IC 50 of 2.5 g/ml and a high selective index of 100 (16).…”

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confidence: 71%

“…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%

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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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confidence: 71%

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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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“…Astrakurkurone seen to be quite effective against clinically important intracellular amastigotes, with significant low IC 50 of 2.5 µg/ml. 69 Further extension of their study demonstrated that astrakurkurone boost the immune efficiency of host cells by generating protective cytokines, interleukin 17 and γ-interferon leading to parasite clearance both…”

Section: 69mentioning

confidence: 99%

“…45 The mechanism behind the promastigocidal activity of astrakurkurone was unveiled by Mallick et al (2015) where the proliferation of L. donovani promastigotes were inhibited by astrakurkurone by selective ROS production leading to mitochondrial dysfunction as well as depleting reduced glutathione. Astrakurkurone seen to be quite effective against clinically important intracellular amastigotes, with significant low IC 50 of 2.5 µg/ml.…”

Section: 69mentioning

confidence: 99%

A Comprehensive Review on Food and Medicinal Prospects of Astraeus hygrometricus

Biswas

Nandi²,

Kuila³

et al. 2017

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“…In contemporary terms, they can be regarded as functional foods that can furnish health benefits beyond the traditional nutrients. 10 Mushrooms are known to be rich sources of various bioactive substances like antioxidant, [11][12][13] antimicrobial, 14,15 immunomodulatory, 16,17 and anticancer 18 substances. Despite all the mentioned health promoting effects, this diverse group is still largely unknown as more than half of the species remain undescribed.…”

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confidence: 99%

Microanatomical and Physicochemical Characterization and Antioxidative Activity of Methanolic Extract of Oudemansiella canarii (Jungh.) Höhn

Acharya¹,

Nandi²,

Dutta³

2019

tjps

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ÖZAmaç: Oudemansiella canarii, gastronomik lezzeti nedeniyle dünya çapında değerli, yenilebilir bir mantardır. Bugüne kadar, bu makrofungusun farmakolojik veya antioksidan özellikleri hakkında kapsamlı bir çalışma bildirilmemiştir. Bu çalışmada, mikro-morfolojik özellikler, moleküler dizi (nrITS rDNA) verisine dayanarak kimliğinin doğrulanması, organoleptik özellikler ve floresan davranışı gibi fizikokimyasal parametrelerinin belirlenmesi amaçlanmıştır. Gereç ve Yöntemler: Toplanan basidiokarplar toz haline getirilmiş ve mikroskobik ve organoleptik değerlendirme için kullanılmıştır. Metanollü ekstrenin antioksidan kapasitelerini değerlendirmek için 2,2-difenil-1-picrylhydrazyl (DPPH) radikal süpürme yöntemi, toplam antioksidan aktivite yöntemleri ve 2,2-azinobis (3-etilbenzotiyazolin-6-sülfonik asit) (ABTS) analizi kullanılmıştır. Fenolik parmakizi analizi için yüksek performanslı sıvı kromatografisi (HPLC) profili alınmıştır. Bulgular: DPPH radikal süpürücü etki tayininde EC 50 değeri 0.912 μg olarak belirlenmiş, toplam antioksidan aktivitenin 15.33 μg askorbik asit eşdeğeri/ mg ekstre olduğu bulunmuş ve ABTS analizinde 12.91 μm TE/mg ekstre ile antioksidan aktivite gösterdiği belirlenmiştir. HPLC kromatogramı 12 pikin Objectives: Oudemansiella canarii is an edible mushroom highly appreciated throughout the world due to its being a gastronomic delicacy. To date, no extensive work has been reported on the pharmacological or antioxidative aspects of this macrofungus. The present study focuses on the micromorphological features, confirmation of its identity based on molecular sequence (nrITS rDNA) data, and determination of its physicochemical parameters such as organoleptic features and fluorescent behavior. Materials and Methods: Collected basidiocarps were powdered and used for microscopic and organoleptic evaluation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, total antioxidant activity methods, and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay were used for evaluating the antioxidant capacities of the methanolic extract. High-performance liquid chromatography (HPLC) analysis profile was also recorded to analyze the phenolic fingerprint. Results: The DPPH radical scavenging activity was determined with an EC 50 value of 0.912 μg, total antioxidant activity was found to be 15.33 μg ascorbic acid equivalent/mg of extract, and the ABTS assay revealed 12.91 μm TE/mg of extract antioxidant activity. The HPLC chromatogram revealed the presence of 12 peaks. Several parameters were tested for the determination of chemical composition, revealing the existence of major bioactive components in the extract in the following order: phenol>flavonoid>ascorbic acid>β-carotene~lycopene. Conclusion:The present work suggests that O. canarii may be considered a novel prospect as a functional food and antioxidant supplement.

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A novel Triterpene from Astraeus Hygrometricus Induces Reactive Oxygen Species Leading to death in Leishmania Donovani

Abstract: We claim the present invention as substantial in depth evidences that mushroom derived active molecules can be exploited as target specific, comparatively nontoxic leads for antileishmanial therapy.

Cited by 41 publications

References 33 publications

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

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

A Comprehensive Review on Food and Medicinal Prospects of Astraeus hygrometricus

Microanatomical and Physicochemical Characterization and Antioxidative Activity of Methanolic Extract of <i>Oudemansiella canarii</i> (Jungh.) Höhn

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