ABSTRACT
Objective To study the effect of procyanidins (PC) on mRNA and protein expression of par-4 and bcl-2 genes in PC12 cells induced by A?_ 25-35 . Methods Cell survival rate was evaluated by MTT assay and apoptosis was analyzed by Hoechst 33258-PI fluorescence staining. The expressions of mRNA and protein for par-4 and bcl-2 were tested by RT-PCR and Western blotting. Results Pretreatment with different concentrations of PC (5、10、20, and 30 mg/L) for 1 h increased the survival rate of PC12 cell in a dose-dependent manner. PC prevented the PC12 cells nuclei from shrinkage, condensation, and cleavage induced by A?_ 25-35 . PC decreased the expression of par-4 mRNA and protein, and increased the expression of bcl-2 mRNA and protein. Conclusion PC can protect PC12 cells from apoptosis induced by A?_ 25-35 in a dose dependent manner. The mechanism of protection is likely related to decreasing the par-4 gene expression and increasing the bcl-2 gene expression.
ABSTRACT
Aim To study the effect of novel AChE inhibitors, 2-phenoxy-indan-1-one derivatives (YKY-1~7), against glutamatic acid-induced neurotoxicity in PC12 cells and on learning & memory impairment in dementia model mice induced by A?25~35 icv Methods The PC12 cells were preincubated with different concentrations of YKY-1~7 for 24 h and subsequently treated by glutamatic acid, at the high concentration of 2 mmol?L-1 for 15 min to induce cytotoxicity. The cell viability was assessed with MTT method.. Dementia model mice were made by intracerebroventricular injection (icv) of aggregated A?25~35. From the next day, the model mice were administered YKY-7 (2.5, 5, 10 mg?kg-1, ig) for 10 consecutive days and sham control mice or A? model control mice received daily ig saline. After the final treatment, the passive avoidance learning was tested, regional cerebral blood flow at cerebral cortex was assessed, and the activity of AChE in the cerebral cortex, hippocampus and blood serum were determined. Results Six out of the seven YKY compounds appeared to be effective against glutamatic acid-induced neurotoxicity in PC12 cells, with YKY-7 demonstrating the most activity. YKY-7 significantly ameliorated the learning and memory ability in dementia model mice induced by A?25-35 icv, slightly and selectively inhibited the cortical and hippocampal AChE, and gently increased the blood flow at cerebral cortex. Conclusion Some of 2-phenoxy-indan-1-one derivatives reported here have protective effects against glutamatic acid induced neurotoxicity in PC12 cells, and improve the learning and memory impairment induced by A?25-35, which may be partly attributable to its selective inhibition of AChE activity in the cerebral cortex and hippocampus.