Objective:Huannao Yicong Decoction(还脑益聪方,HYD),an effective herbal formul against Alzheimer\'s disease (AD),has been proven to have neuroprotective action in amyloid β-protein1-42 (A β 1-42)-induced rat model.This study was designed to characterize mechanisms by which HYD leads to suppression of inflammation and apoptosis in the brains of A β 1-42-induced rat.Methods:A total of 72 rats were divided into 6 groups,which were referred to as:sham operation group,model group,donepezil-treated group,HYD low-dose group (HYDL),HYD middle-dose group (HYDM) and HYD high-dose group (HYDH).Rats in HYDL,HYDM and HYDH were injected with A β1-42 at the CA1 region of hippocampus to form AD model and were fed the HYD extract at different dose of 3.78,7.56 and 18.90 g crude drug/kg.The behavioral changes of rats were evaluated by Morris water maze (MWM) before sacrifice.Pathological changes of the brain tissue were evaluated using hematoxylin eosin (HE) staining.The levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) were measured by radioimmunoassay.The levels of A β and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein (Bcl-2),Bcl-2-associated X protein (Bax),cysteine-aspartic protease (caspase)-3,-8,-9 and-12 in serum were measured by immunohistochemistry.Results:Compared with the sham operation group,the spatial learning and memory abilities of AD rats were significantly decreased (P＜0.05 or P＜0.01;Expressions of IL-1,TNF-α,Aβ and apoptosis-signaling proteins caspase-3,-8,-9,-12 were significantly up-regulated (P＜0.05 or P＜0.01).The ratio of Bcl-2 to Bax were significantly decreased in the model group (P＜0.01).When treated with HYD extract,the spatial learning and memory abilities of AD-model rats were significantly increased (P＜0.05 or P＜0.01),IL-1,TNF-α,A β,caspase-3,-8,-9 and-12 were down-regulated (P＜0.05 or P＜0.01),and the ratio of Bcl-2 to Bax were reduced (P＜0.05 or P＜0.01).Conclusions:HYD extract can improve the leaming and memory ability deficits,alleviate the inflammatory response and pathological manifestations induced by A β1-42 injection in the rat model of AD.HYD down-regulates the levels of IL-1,TNF-α and A β,and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3,-8,-9,and-12.