Kai-Xin-San, a Chinese Herbal Decoction, Accelerates the Degradation of β-Amyloid by Enhancing the Expression of Neprilysin in Rats

This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal decoction used to treat amnesia) on the degradation of Aβ and further elucidate the mechanism of KXS on Aβ-induced memory dysfunction. After pretreatment with KXS (1.08 g/kg/day) for two weeks, Aβ(42) (2 μL, 200 μM) was injected into rat hippocampus to induce cognitive dysfunction. Morris water maze (MWM) test was developed to evaluate cognitive performance in rats. Hippocampal neurons were observed by histological staining using Hematoxylin-Eosin (HE) methods. Levels of exogenous Aβ(42), which was injected into the hippocampus, were continually measured through a special Enzyme-linked immunoassay (ELISA) kit to observe the catabolic process of Aβ in the brain. Similarly, Aβ degradation in PC12 cells was also investigated using the ELISA kit. The expressions of Aβ degeneration enzymes, including neprilysin (NEP), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE), were detected by western blotting to elucidate Aβ reduction mechanism. Our results showed that KXS prevented Aβ(42)-induced cognitive impairment and attenuated hippocampus neuronal damage caused by Aβ(42). Moreover, KXS could accelerate Aβ(42) degradation in Aβ(42) injected rats. Furthermore, NEP, an Aβ degradation enzyme, was increased in the hippocampus while ECE and ACE, other two Aβ-degrading enzymes, were not changed. KXS accelerated Aβ degradation in PC12 cells. Our findings revealed that KXS facilitated the degradation of Aβ(42) by increasing the expression of NEP in rat hippocampus. By reducing the Aβ burdens, KXS protected hippocampal neurons, leading to the improvement of cognitive function in rats.