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

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.