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β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62
Author(s) -
Huang LiPing,
Deng MinZhen,
He YuPing,
Fang YongQi
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12344
Subject(s) - hydroxydopamine , intraperitoneal injection , medial forebrain bundle , autophagy , pharmacology , oxidopamine , chemistry , endocrinology , medicine , apoptosis , striatum , dopamine , dopaminergic , biochemistry , substantia nigra
Summary In this study, we investigated Beclin‐1, light chain ( LC )3B, and p62 expression in 6‐hydroxydopamine (6‐ OHDA )‐induced parkinsonian rats after β‐asarone and levodopa ( l ‐dopa) co‐administration. Unilateral 6‐ OHDA injection into the medial forebrain bundle was used to create the models, except in sham‐operated rats. Rats were divided into eight groups: sham‐operated group; 6‐ OHDA model group; madopar group (75 mg/kg, per os (p.o.)); l ‐dopa group (60 mg/kg, p.o.); β‐asarone group (15 mg/kg, p.o.); β‐asarone + l ‐dopa co‐administered group (15 mg/kg + 60 mg/kg, p.o.); 3‐methyladenine group (500 nmol, intraperitoneal injection); and rapamycin group (1 mg/kg, intraperitoneal injection). Then, Beclin‐1, LC 3B, and p62 expression in the mesencephalon were detected. The mesencephalon was also observed by transmission electron microscope. The results showed that Beclin‐1 and LC 3B expression decreased and that p62 expression increased significantly in the madopar, l ‐dopa, β‐asarone, and co‐administered groups when compared with the 6‐ OHDA model. Beclin‐1 and LC 3B expression in the β‐asarone and co‐administered groups were less than in the madopar or l ‐dopa groups, whereas p62 expression in the β‐asarone and co‐administered groups was higher than in the madopar or l ‐dopa groups. In addition, a significant decrease in autophagosome was exhibited in the β‐asarone and co‐administered groups when compared with the 6‐ OHDA group. Our findings indicate that Beclin‐1 and LC 3B expression decreased, whereas p62 expression increased after co‐administration treatment. In sum, all data suggest that the co‐administration of β‐asarone and l ‐dopa may contribute to the treatment of 6‐ OHDA ‐induced damage in rats by inhibiting autophagy activity.