Scutellaria Barbata flavonoids inhibit the abnormal generation of Aβ and NFT in brain and affect the related enzymes expression induced by composited Aβ in rats

HOU Xiao-chan; WANG Chong-zhi; WANG Zi-yi; ZHAO Wen-jing; GUO Ke; MA Shuai; WU Xiao-guang; SHANG Ya-zhen

Abstract：Objective:To investigate the effects of Scutellaria barbata flavonoids (SBF) on Aβ and NFT abnormal generation and the related enzymes expression in rats induced by amyloid beta protein 25-35 (Aβ25-35) in combination with AlCl3 and rhTGF-β1 (composited Aβ).Methods:Male Sprague Dawley (SD) rats were microinjected composited Aβ into cerebral ventricle to establish memory impairment model.Rats with impaired memory were screened on day 45 of operation.The successful model rats were randomly grouped and administered 35,70 or 140 mg· kg-1 SBF daily for 38 d.All the rats were killed by decapitation 60 min after the last administration.The brain was gently separated on ice.Congo red and silver nitrate staining methods were used to determine the Aβ and NFT formation.Reverse transcription polymerase chain reaction (RT-PCR) method was supplied to measure the mRNA expression levels of beta-amyloids protein 1-40 (Aβ1-40) and Aβ1-42.Quantitative real-time polymerase chain reaction (qPCR) method was used for determination of α,β and γ secretases mRNA expression levels.Results:The composited Aβ given by intracerebroventricular injection to rats resulted in increases in Aβ congo red stained and N FT silver nitrate stained cells and the mRNA expression levels of Aβ1-40,Aβ1-42 and β-secretase (P＜0.05,P＜0.01),and decrease in mRNA expression level of γ-secestase (P＜0.05).SBF at 35,70 and 140 mg·kg-1 inhibited Aβ and NFT formation in different degrees (P ＜0.05,P ＜0.01),and reversed the increases in mRNA expression level of Aβ1-40 and Aβ1-42 after administration for 38 d (P ＜ 0.01).SBF at 70 and 140 mg·kg-1 strongly lowered the increase in β-secretase mRNA expression (P ＜ 0.01),and 35 and 140 mg· kg-1 SBF further decreased γ-secretase mRNA expression (P ＜ 0.01).The mRNA expression level of α-secretase had no significant change in all the groups.Conclusion:SBF can inhibit Aβ and NFT abnormal production and regulate β/γ-secretases expressions induced by composited Aβ.