Background: Danshensu is one of active constituents in the extracts of Danshen which is a traditional Chinese medical herb. Objective: This study aimed to investigate neuroprotective effects of Danshensu on rotenone-induced Parkinson's disease (PD) in vitro and in vivo. Materials and Methods: SH-SY5Y human neuroblastoma cell line were pretreated with Danshensu and then challenged with rotenone. Male C57/BL6 mice were intragastrically administered with Danshensu (15, 30, or 60 mg/kg) followed by oral administration with rotenone at a dose of 30 mg/kg, once daily for 28 d. Pole and rotarod tests were investigated at 28 d. Then, tyrosine hydroxylase (TH) was evaluated with immunohistochemistry and western blot methods. Dopamine and its metabolites were detected by high-performance liquid chromatography with fluorescence detection. Malondialdehyde (MDA) and GSH in striatum were measured. The proteins of PI3K/AKT/Nrf2 pathway were assayed by western blot method. Results: Danshensu attenuated the rotenone-induced toxicity and suppressed reactive oxygen species (ROS) generation in SH‑SY5Y cells. Behavioral tests showed that rotenone-challenged mice displayed motor dysfunction. However, treatment with Danshensu improved motor dysfunction induced by rotenone. Danshensu treatment increased not only the number of TH positive neurons and the expression of TH, but also the dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents. Danshensu also reduced MDA content and increased GSH level in striatum. Moreover, the expressions of p-PI3K, p-AKT, Nrf2, hemeoxygenase (HO-1), glutathione cysteine ligase regulatory subunit (GCLC), glutathione cysteine ligase modulatory subunit (GCLM) were significantly increased and the expression of Keap1 was decreased in Danshensu groups. Conclusion: These results suggest that the neuroprotective effects of Danshensu against rotenone toxicity are attributed to the anti-oxidative properties by activating PI3K/AKT/Nrf2 pathway and increasing Nrf2-induced expression of HO-1, GCLC, and GCLM, at least in part.

Key words: Danshensu, Parkinson’s disease, Motor dysfunction, rotenone