Objective: To investigate the neuroprotective effect and autophagy of artesunate in mice with experimental autoimmune encephalomyelitis.
METHODS: Forty-eight female C57BL/6 mice were randomly divided into 4 groups: blank group, model group, low-dose artesunate group, and high-dose group, with 12 mice in each group. The EAE model was established by using MOG35-55 polypeptide. Artesunate (10 mg/(kg·d), 50 mg/(kg·d)) was intraperitoneally injected into the low-dose group and high-dose group of artesunate respectively for 10 consecutive days to observe the incidence of the mice. Brain tissue was subjected to luxol fast Blue (LFB) staining was used to observe demyelination, and Western blot was used to detect the expression of autophagy-related proteins LC3-I and LC3-II.
Results: None of the mice in the blank group had the disease, but the mice in the model group and each dose of artesunate had different degrees of tail drooping, unsteady walking, and hind limb weakness. Compared with the model group, each dose of artesunate group , the onset latency, peak period delay, and neurological function scores decreased, the high-dose group and the lower-dose group had a significant effect (P<0.05), and="" there="" was="" no="" statistical="" significance="" between="" the="" low-dose="" group="" high-dose="" in="" peak="" data-ke-onset="" period="" p="">0.05). ②LFB Staining showed that the arrangement of myelin in the brain tissue of the model group was loose, disordered, and low-stained, and the staining of the myelin in each dose of artesunate was improved. ③ Western blot detected the LC3-I and LC3-II bands in the model group compared with the blank group. The optical density value and LC3-II/LC3-I ratio increased (P<0.01); compared with the model group, the LC3I, LC3II band optical density value and the LC3-II/LC3-I ratio of each artesunate dose group Both decreased (P<0.01), and the high-dose group had a significant effect in the lower-dose group (P<0.05).
Conclusion: Artesunate has neuroprotective effect on EAE mice and reduces the demyelination of brain tissue, and the mechanism may be related to reducing autophagy by down-regulating LC3-I, LC3-II and LC3-II/LC3-I .