【Abstract】 Objective The study was aimed to investigate the effect of Panax Notoginseng Saponins (PNS) on PI3K/Akt and PLCγ1/PKC pathway in SAMP8 mice. MethodsSAMP8 mice were randomly divided into model group，PNS high-dosage group and PNS low-dosage group. SAMR1 was considered as a control strain of SAMP8. The mice were orally administrated with PNS once daily for 2 months. After treatment，Nissl staining was used to observe the morphologies of neurons in hippocampal CA1 region. Enzyme activity kit was used to activity of PKC. RT-PCR assay was performed to detected the mRNA level of PI3K and Akt. Western blot assay was utilized to detect the levels of PI3K，Akt and p-Akt. ResultsThe result of Nissl staining showed that the number of neurons were reduced and the CA1 region neurons of the model group exhibited irregular and loose arrangements. PNS could alleviate neuronal injury in the hippocampal CA1 region. Compared with model group，PKC activities were significantly enhanced in PNS groups(P<0.05). The Results of RT-PCR and Western blot assays showed that compared with the model group (P<0.05)，the mRNA contents of PI3K，Akt，PLCγ1 and PKC in PNS high-dose group were remarkably increased，and the protein expression levels of PI3K，Akt，p-Akt and p- PLCγ1 were significantly increased in PNS groups (P<0.05). ConclusionPNS activates PI3K/Akt and PLCγ1/PKC pathway，which may be the mechanism of PNS alleviating neuronal injury.