Effects of asiatic acid on MPTP-induced Parkinson's disease-like motor symptoms in mice / 中成药

ABSTRACT

AIM To investigate the effects of asiatic acid (AA) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD)-like motor symptoms in mice and its neuroprotective mechanism.METHODS Forty-five male C57BL/6 mice,except the nine mice in control group,were induced to be the PD models by peritoneal injection of 25 mg/kg MPTP for seven days and then were randomly assigned to model group,low-dose,high-dose AA groups and positive control group.Both the control group and the model group were administered with 0.5％ sodium carboxyl methyl cellulose (CMC-Na) solution,the AA groups were dosed with 12.5 mg/kg and 25 mg/kg AA,respectively,and the positive control group was given 75 mg/kg daily intragastric gavage of levodopa for eleven days.On the twelfth day,behavioral tests were performed.Tyrosine hydroxylase (TH) positive cells in substantia nigra were detected by immunohistochemistry.The mRNA expressions of iNOS,COX-2,TNF-α,IL-1β,and malonaldehyde (MDA) content in midbrain were measured.The levels of IL-1 β and TNF-α in the serum were detected using ELISA kits.RESULTS The mice treated with asiatic acid performed better in behavior tests than those in the model group (P ＜0.05,P ＜0.01).In addition,asiatic acid effectively protected the dopaminergic neurons in the substantia nigra due to upregulated TH expression and increased number of TH positive cells (P ＜ 0.05).The asiatic acid-treated mice had their mRNA expressions of IL-1β,TNF-α,iNOS and COX-2 in midbrain markedly suppressed (P ＜0.05,P ＜0.01),and a significant MDA level decrease in the midbrain tissue as well (P ＜ 0.01).Furthermore,reductions of IL-1 β and TNF-α contents in the serum were observed (P ＜ 0.05,P ＜ 0.01).CONCLUSION Asiatic acid attenuates motor dysfunction and dopaminergic neuronal deficits in PD mice,and the neuroprotective mechanisms may attribute to its anti-oxidative and anti-inflammatory activities.