Objective: To investigate the effects of Dihuang Yinzi on mitochondrial biosynthesis

oxidative stress as well as learning and memory ability in Alzheimer's disease (AD) rats. Method: Totally 120 male rats were randomly distributed into sham operation group

AD model group

Aricept group

high-

moderate and low-dosage Dihuang Yinzi groups. Animals in all groups except the sham operation group were injected with β-amyloid protein 1-42(Aβ1-42) via lateral ventricles to establish AD model. Corresponding drug were given via intragastric administration

while those in sham operation group and AD model group were administrated with the same volume of normal saline. The administrations were performed once a day and were consecutively carried out for 30 days. The behavior of rats was assessed with avoiding dark test and Y-maze test

respectively. After behavioral tests

the expression of cAMP responsive element-binding protein (CREB) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-lα) were determined by Western blot. Activities of respiratory chain complex I

Ⅱ

Ⅲ

and Ⅳ

the level of malondialdehyde (MDA)

and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mitochondria of brain tissues were detected respectively. Result: Dihuang Yinzi can significantly improve the learning memory ability and working memory ability of AD rats. In comparison with AD model group

Dihuang Yinzi treatment could increase the stay-latency and decrease the error times of AD rats in avoiding dark test (P< 0.05

P< 0.01). The spontaneous alternation in AD rats was significantly increased by Dihuang Yinzi in Y-maze test (P< 0.05

P< 0.01). Dihuang Yinzi could significantly up-regulate the phosphorylation of cyclic adenosine monophosphae and the expression of PGC-lα and significantly increase the activity of respiratory chain complex Ⅰ

Ⅲ and Ⅳ in AD rats (P<0.01)

but had no obvious effect on the activity of complex Ⅱ Dihuang Yinzi could also reduce the level of cerebral MDA (P<0.01) and improve the activities of SOD and GSH-Px(P<0.05

P<0.01). Conclusion: Dihuang Yinzi can improve the cognition of AD rats significantly via activating the CREB/PGC-1α pathway

increase the mitochondrial biosynthesis and mitochondrial respiratory chain enzyme activity

improve mitochondrial dysfunction

and improve the body's ability against oxidative damages

thereby improving learning memory ability and working memory ability in AD rats by enhancing antioxidant enzyme activity.