Neuroprotective and antioxidant lanostanoid triterpenes from the fruiting bodies of Ganoderma atrum.

Five new lanostanoid triterpenes were isolated from the ethanol extract of the fruiting bodies of Ganoderma atrum. The structures of the isolated compounds were established based on 1D and 2D ((1)H-(1)H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for neuroprotective activities against 6-OHDA-induced cell death in SH-SY5Y cells and radical scavenging activities. As a result, compounds 2 and 5 exhibited potent neuroprotective activity against 6-OHDA-induced cell death in SH-SY5Y cells with the lowest IC50 value (0.5 µM) while compounds 1, 3 and 4 possessed significant neuroprotective activity with IC50 value less than 10 µM. Additionally, all tested compounds 1-6 showed the comparable free radical scavenging activities with the standard drug trolox in both ABTS (+) and DPPH experiment.

CXCR4 Antagonist AMD3100 Suppresses the Long-Term Abnormal Structural Changes of Newborn Neurons in the Intraventricular Kainic Acid Model of Epilepsy.

Abnormal hippocampal neurogenesis is a prominent feature of temporal lobe epilepsy (TLE) models, which is thought to contribute to abnormal brain activity. Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in adult neurogenesis. We investigated whether treatment with the CXCR4 antagonist AMD3100 suppressed aberrant hippocampal neurogenesis, as well as the long-term consequences in the intracerebroventricular kainic acid (ICVKA) model of epilepsy. Adult male rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), and post-SE rats treated with AMD3100. Animals in each group were divided into two subgroups (acute stage and chronic stage). We used immunofluorescence staining of BrdU and DCX to analyze the hippocampal neurogenesis on post-SE days 10 or 74. Nissl staining and Timm staining were used to evaluate hippocampal damage and mossy fiber sprouting, respectively. On post-SE day 72, the frequency and mean duration of spontaneous seizures were measured by electroencephalography (EEG). Cognitive function was evaluated by Morris water maze testing on post-SE day 68. The ICVKA model of TLE resulted in aberrant neurogenesis such as altered proliferation, abnormal dendrite development of newborn neurons, as well as spontaneous seizures and spatial learning impairments. More importantly, AMD3100 treatment reversed the aberrant neurogenesis seen after TLE, which was accompanied by decreased long-term seizure activity, though improvement in spatial learning was not seen. AMD3100 could suppress long-term seizure activity and alter adult neurogenesis in the ICVKA model of TLE, which provided morphological evidences that AMD3100 might be beneficial for treating chronic epilepsy.