Tongxinluo improves cognition by decreasing ß-amyloid in spontaneous hypertensive rats.

ABSTRACT

ß-Amyloid (Aß) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aß deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aß using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60days. Cognition was evaluated with a Morris Water Maze (MWM). Aß in the brain was detected by western blot, ELISA and Thioflavin-S staining. Western blot and RT-PCR were employed to exam the expression of receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein-1 (LRP-1) and amyloid precursor protein (APP). After TXL treatment for 60days, compared with the vehicle, the number of crossed platform and the time spent in the target quadrant increased in parallel with the increasing length of treatment in MWM. Moreover, the Aß in the hippocampus significantly decreased compared to the vehicle group, both in western blot and ELISA. Additionally, TXL reduced RAGE expression in a dose- and time-depended manner, but LRP-1 expression had no difference between TXL groups and vehicle groups. Furthermore, the ß-secretase expression was significantly decreased compared to the vehicle group, but APP expression had no difference. In conclusion, TXL improved cognition and decreased Aß in SHRs in a dose- and time-dependent manner, the underlying mechanism may involved in inhibiting RAGE and ß-secretase expression.