Rosmarinic Acid Alleviates Inflammation, Apoptosis, and Oxidative Stress through Regulating miR-155-5p in a Mice Model of Parkinson's Disease.

ABSTRACT

Parkinson's disease (PD) is the second most common neurodegenerative disorder mainly occurring in the elderly. MicroRNA-155-5p (miR-155-5p) plays a vital role in neurodegenerative disease and has been reported to be regulated by rosmarinic acid (RA). In our previous study, it was found that RA could improve motor function and alleviate inflammatory responses in a mice model of PD. This study aimed to investigate the role of miR-155-5p in RA-treated PD mice. The PD mice model was established by injecting mice with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and treated with RA or/and miR-155-5p agomir. The effects of miR-155-5p agomir on motor function, microglial activation, inflammation, apoptosis, and oxidative stress were analyzed by performing a behavioral test, ionized calcium-binding adapter molecule 1 staining, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, tyrosine hydroxylase (TH)-terminal dUTP nick end labeling double staining, TH-cleaved-caspase 3 double staining, and assessment of antioxidative parameters in RA-treated PD mice. The interaction between miR-155-5p and suppressor of cytokine signaling 1/nuclear factor erythroid 2-related factor 2 was validated using dual-luciferase reporter assay. MiR-155-5p up-regulation inhibited the alleviation of motor deficits caused by RA in PD mice, as evidenced by increasing descending time, decreasing limb movement score, increasing the time crossing the beam, and decreasing the times of front limb use. MiR-155-5p up-regulation could elevate microglial activation, inflammation, apoptosis, and oxidative stress in RA-treated PD mice. In conclusion, RA was able to alleviate PD by regulating miR-155-5p, suggesting that miR-155-5p could be used as a therapeutic target for PD treatment.