Objective: To investigate the neuroprotective effect and autophagy of artesunate on experimental autoimmune encephalomyelitis (EAE) mice.
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. The low-dose artesunate group and the high-dose group were given intraperitoneal injection of artesunate (10 mg/(kg·d), 50 mg/(kg·d)), respectively, for 10 consecutive days, and the incidence of the mice was observed. The 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. The artesunate dose groups were compared with the model group. , onset latency, delayed peak period, and decreased neurological function scores, the high-dose group and the lower-dose group had a significant effect (P<0.05), and="" there="" was="" no="" significant="" difference="" between="" the="" low-dose="" group="" high-dose="" in="" peak="" 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 in 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 .