Neuroprotective Effects of β-Asarone Against 6-Hydroxy Dopamine-Induced Parkinsonism via JNK/Bcl-2/Beclin-1 Pathway

Abstract

β-asarone, a major component of Acorus tatarinowii Schott, has positive effects in neurodegeneration disease, however, its effect on the Parkinson's disease (PD) remains unclear. In this study, the effects of β-asarone on behavioral tests, neurotransmitters, tyrosine hydroxylase (TH), and α-synuclein (α-syn) were investigated in 6-hydroxydopamine (6-OHDA) induced rats. Furthermore, the JNK/Bcl-2/Beclin-1 autophagy pathway was also studied. The results showed that β-asarone improved the behavioral symptoms of rats in the open field, rotarod test, initiation time, and stepping time. And it increased the HVA, Dopacl, and 5-HIAA levels in striatum but not the DA and 5-HT levels. After administration of β-asarone, the TH level was elevated but the α-syn was declined in rats. It inhibited the expressions of LC3-II, but increased the p62 expression in SN4741 cells. Moreover, it affected the expressions of Beclin-1, Bcl-2, JNK, and p-JNK in vivo. We deduced that β-asarone may firstly downregulate expressions of JNK and p-JNK, and then indirectly increase the expression of Bcl-2. And the function of Beclin-1 could be inhibited, which could inhibit autophagy activation. Collectively, all data indicated that β-asarone may be explored as a potential therapeutic agent in PD therapy.

Neurotoxic Effect of Benzo[a]pyrene and Its Possible Association with 6-Hydroxydopamine Induced Neurobehavioral Changes during Early Adolescence Period in Rats

“…Our results showed significant alleviation of striatal dopamine level following B[a]P administration and the result finds support from previous report [ 20 ]. Similarly, 6-OHDA administration leads to significant decrease in dopamine level as compared to B[a]P and the above findings are in agreement with previous report [ 34 , 35 ]. The possible effect of neonatal B[a]P administration on striatal dopamine level during adolescence was found to be linked with the effect of 6-OHDA.…”

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

“…In this respect, it should be stressed that JNKs can be activated by a number of factors implicated in PD such as toxicants [ 16 ] and unfolded/misfolded proteins [ 17 ]. Some studies have demonstrated that JNKs are significantly activated in several common animal models of PD induced by neurotoxins such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), 6-OHDA (6-hydroxydopamine) or LPS (lipopolysaccharide) [ 18 , 19 , 20 , 21 ]. Genetic deletion of JNK2 and JNK3 protects against MPTP-induced neurodegeneration in mice [ 22 ].…”

β‐asarone and levodopa co‐administration increase striatal dopamine level in 6‐hydroxydopamine induced rats by modulating P‐glycoprotein and tight junction proteins at the blood‐brain barrier and promoting levodopa into the brain

“…30,31 Furthermore, our previous results also suggested that b-asarone showed neuroprotective effects on 6-hydroxydopamine (6-OHDA) induced parkinsonian rats. 32 We also found that basarone and L-dopa co-administration could increase striatal levels of L-dopa and DA in healthy rats. 33 However, the effects on neurotransmitters, BBB and P-gp after co-administration treatment of b-asarone and L-dopa in the 6-OHDA induced PD rats have not been reported before.…”

“…Some studies proposed that β ‐asarone effectively reversed multi‐drug resistance (MDR) by inhibiting P‐gp function and expression in Caco‐2 cells as well as reduced P‐gp expression in prefrontal cortex in pentylenetetrazol kindling rats . Furthermore, our previous results also suggested that β ‐asarone showed neuroprotective effects on 6‐hydroxydopamine (6‐OHDA) induced parkinsonian rats . We also found that β ‐asarone and L‐dopa co‐administration could increase striatal levels of L‐dopa and DA in healthy rats .…”