Selective in vitro inhibition of Leishmania donovani by a semi-purified fraction of wild mushroom Grifola frondosa

Exp Parasitol. 2018 Sep;192:73-84. doi: 10.1016/j.exppara.2018.07.006. Epub 2018 Jul 21.

Abstract

The current study was designed to assess the anti-leishmanial effect of a semi-purified fraction of wild mushroom Grifola frondosa against Leishmania donovani, in vitro. A total of five extracts from three wild mushrooms [Grifola frondosa (family, Meripilaceae) Laetiporus sulphurous (family, Polyporaceae) and Meripilus giganteus (family, Meripilaceae) were explored for novel anti-leishmanial leads against promastigotes. The ethanol extract of G. frondosa was selected as the most efficient against L. donovani promastigotes (IC50: 93.9 μg/mL). A semi-purified fraction was obtained from an active ethanol extract of G. frondosa and found to inhibit the survival of promastigotes of L. donovani (MHOM/IN/83/AG83) significantly (IC50: 20.37 μg/mL) and it also had some effect against L. major LV39 (MRHO/Sv/59/P strain) and L. tropica WR683 (MHOM/SU/58/OD) strains at higher concentrations (IC50: 46.08 μg/mL and 53.79 μg/mL respectively). The semi-purified fraction also interfered in lipid biosynthesis, altered parasite morphology and induced apoptosis in L. donovani promastigotes. The semi-purified fraction was also effective against intracellular amastigotes in infected macrophages and enhanced the release of nitric oxide and pro-inflammatory cytokines, in vitro. Interestingly, the 50% inhibitory concentration of the semi-purified fraction against the intracellular amastigotes (IC50: 2.48 μg/mL) was much lower in comparison to promastigotes (IC50: 20.37 μg/mL). The semi-purified fraction was found to inhibit the intracellular amastigotes slightly more efficiently in comparison to conventional anti-leishmanial drugs; sodium antimony gluconate, amphotericin B, miltefosine and paromomycin and noticeably non-toxic towards host splenocytes. The findings of the present study established that G. frondosa might be a natural resource for development of a new anti-leishmanial lead.

Keywords: Apoptosis; Grifola frondosa; Leishmania donovani; Mushrooms; Nitric oxide; Pro-inflammatory cytokines; ROS.

MeSH terms

  • Animals
  • Chromatography, Gel
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Grifola / chemistry*
  • Inhibitory Concentration 50
  • Leishmania donovani / drug effects*
  • Leishmania donovani / pathogenicity
  • Leishmania donovani / ultrastructure
  • Leishmania major / pathogenicity
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Polyporaceae / chemistry
  • Polyporales / chemistry
  • Spleen / cytology
  • Spleen / drug effects
  • Virulence

Substances

  • Cytokines