Neuroprotective mechanism of Kai Xin San: upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation

Abstract

<i>Kai Xin San</i> is a Chinese herbal formula composed of <i>Radix Ginseng</i>, <i>Poria</i>, <i>Radix Polygalae</i> and <i>Acorus Tatarinowii Rhizome</i>. It has been used in China for many years for treating amnesia. <i>Kai Xin San</i> ameliorates amyloid-β (Aβ)-induced cognitive dysfunction and is neuroprotective <i>in vivo</i>, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme (IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ₄₂ (200 μM, 5 μL) into the hippocampus and subsequently administered <i>Kai Xin San</i> (0.54 or 1.08 g/kg/d) intragastrically for 21 consecutive days. Hematoxylin-eosin and Nissl staining revealed that <i>Kai Xin San</i> protected neurons against Aβ-induced damage. Furthermore, enzyme-linked immunosorbent assay, western blot and polymerase chain reaction results showed that <i>Kai Xin San</i> decreased Aβ₄₂ protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that <i>Kai Xin San</i> facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.