Evaluation of the Anticonvulsant, Anxiolytic, Sedative, and Neuroprotective Activities of Polysaccharides from Mycelium of Two Ganoderma Species

Abstract

Background. Ganoderma lucidum has been used as a medicinal mushroom since centuries in East Asia. Recent reports have shown that metabolites isolated from Ganoderma species have shown effects on central nervous system. Objective. To determine the neuroprotective, anticonvulsant, anxiolytic, and sedative effects of Ganoderma sp. and Ganoderma curtisii polysaccharides. Methods. Polysaccharides (Gsp-PS2 or Gc-PS2) were isolated from two Ganoderma mycelia submerged cultures. Acute toxicity effects of Gc-PS2 or Gsp-PS2 on mice were treated orally with doses of 50 - 2000 mg/kg. Anticonvulsant activity was determined using three chemoconvulsants: kainic acid (KA), strychnine, or pentylenetetrazole (PTZ). Anxiolytic-like effects were determined using the elevated plus maze test on mice. GABA release evoked by GC-PS2 or Gsp-PS2 content was determined by HPLC. Neuroprotective effects of Gsp-PS2 or Gc-PS2 were determined by glial activation, histopathological changes, and immunohistochemistry. Results. Gc-PS2 or Gsp-PS2 showed neuroprotective activity by diminishing neuronal death, reducing glial activation and Neu-N expression levels. Gsp-PS2 or Gc-PS2 inhibited convulsions in the KA model. An anxiolytic-like, but not a sedative effect was reported in mice treated with Gc-PS2 or Gsp-PS2. Polysaccharides Gc-PS2 or Gsp-PS2 evoked endogenous GABA release and increased its concentration within the incubation medium. Pretreatment with Gsp-PS2 or Gc-PS2 showed a reduction of the LPSinduced NO production. Gc-PS2 or Gsp-PS2 did not produce toxic effects. Conclusion. Ganoderma sp. or Ganoderma curtisii polysaccharides showed neuroprotective and anticonvulsant activities in animal models. The anticonvulsant activity may involve the GABAergic neurotransmision. Key words: Ganoderma sp, Ganoderma curtissi, a- and b-glucan, Neuroprotective, Anticonvulsant, GABA