No abstract

Abstract. The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 μM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 μM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 μΜ. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca 2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

Ferulic acid (50 and 100 mg/kg) reversed the step-through latency shortened by scopolamine and cycloheximide but not by p-chloroamphetamine in an inhibitory avoidance performance. Piracetam and tacrine might reverse the step-through latency shortened by the above drugs. However, ferulic acid, piracetam or tacrine alone at any used dose did not influence motor activity produced by non-shock rats. Furthermore, the cerebral blood flow of rats treated with ferulic acid, piracetam or tacrine was enhanced. From these results, we suggest that the potency of ferulic acid was better than that of piracetam, but its action mechanism was somewhat different from that of piracetam and tacrine. Thus, the attenuating effects of ferulic acid on the avoidance performance impairment were related to memory processes, and might be enhancing the cholinergic activities and cerebral blood circle.

This study compared the antioxidant activity of various parts of Broussonetia papyrifera (BP), and further evaluated the protective effects of BP against hydrogen peroxide (H(2)O(2))-induced neuronal injury in human neuroblastoma SH-SY5Y cells. Among four BP parts, BP radix and leaf possessed the best scavenging activities for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical, and H(2)O(2). These two BP parts also had higher phenolic and phenylpropanoid contents. Following exposure of cells to H(2)O(2), there was a marked decrease in cell survival, intracellular glutathione levels, and antioxidant enzymes, as well as an increase in intracellular oxidative stress. DNA fragmentation was also observed, but pretreatment of the cells with BP radix but not leaf prior to H(2)O(2) exposure blocked these H(2)O(2)-induced cellular events. The present findings indicate that BP radix exerts protective effects against H(2)O(2) toxicity via its free radical scavenging activity, which might be due to its total phenolic compounds.

Puerarin at 10-50 mg/kg attenuated the mecamylamine- but not scopolamine-induced acquisition impairment of inhibitory avoidance performance in an inverse U-shape manner. p-Chloroamphetamine- and dizocilpine-induced acquisition impairment were reversed by puerarin at 25-50 mg/kg. Both piracetam, and tacrine attenuated impairment of inhibitory avoidance performance induced by all used drugs. Furthermore, puerarin, piracetam and tacrine alone did not alter step-through latency in the training trail but puerarin at 50 mg/kg and tacrine plus mecamylamine prolonged it in comparison with mecamylamine alone. From these results, we suggest that puerarin attenuated the deficits of inhibitory avoidance performance induced by mecamylamine, p-chloroamphetamine, and dizocilpine, the effects were related to increasing cholinergic activity via nicotinic but not muscarinic receptors, activating NMDA receptors, and decreasing serotonergic neuronal activity.