28-day oral safety evaluation of extracellular polysaccharopeptides produced in submerged culture from the turkey tail medicinal mushroom Trametes versicolor (L.:Fr.) Pilát LH-1 in mice.

Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a variety of pharmacological activities. Its intracellular polysaccharopeptides are widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained from submerged culture exhibits significant immunomodulatory activity. In this in vivo study, we further evaluated the safety of orally administered LH-1 ePSP using both male and female ICR mice. The LH-1 ePSP was orally administered to mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day (high dose) for 28 days. Clinical observations, growth, food consumption, histopathological examination, and clinical biochemical analyses revealed no adverse effects of LH-1 ePSP in mice. There were no significant differences in the results of target organ weights, hematological analyses, and urinalysis examination among groups. However, male mice that ingested high doses of LH-1 ePSP tended to have decreased lung weights and platelet numbers. In conclusion, the results of the present study suggested that oral administration of LH-1 ePSP for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity supports the potential use of LH-1 ePSP as a food or dietary supplement.

Corticofugal modulation of acoustically induced Fos expression in the rat auditory pathway.

To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC.