TY - JOUR
T1 - Neurotrophic Effect of Asiatic acid, a Triterpene of Centella asiatica Against Chronic 1-Methyl 4-Phenyl 1, 2, 3, 6-Tetrahydropyridine Hydrochloride/Probenecid Mouse Model of Parkinson’s disease
T2 - The Role of MAPK, PI3K-Akt-GSK3β and mTOR Signalling Pathways
AU - Nataraj, Jagatheesan
AU - Manivasagam, Thamilarasan
AU - Justin Thenmozhi, Arokiasamy
AU - Essa, Musthafa Mohamed
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson’s disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD. AA treatment for 5 weeks significantly attenuated MPTP/p induced motor abnormalities, dopamine depletion and diminished expressions NTFs and tyrosine kinase receptors (TrKB). We further, revealed that AA treatment significantly inhibited the MPTP/p-induced phosphorylation of MAPK/P38 related proteins such as JNK and ERK. Moreover, AA treatment increased the phosphorylation of PI3K, Akt, GSK-3β and mTOR, suggesting that AA activated PI3K/Akt/mTOR signalling pathway, which might be the cause of neuroprotection offered by AA. The present findings provided more elaborate in vivo evidences to support the neuroprotective effect of AA on dopaminergic neurons of chronic Parkinson’s disease mouse model and the potential of AA to be developed as a possible new therapeutic target to treat PD.
AB - Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson’s disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD. AA treatment for 5 weeks significantly attenuated MPTP/p induced motor abnormalities, dopamine depletion and diminished expressions NTFs and tyrosine kinase receptors (TrKB). We further, revealed that AA treatment significantly inhibited the MPTP/p-induced phosphorylation of MAPK/P38 related proteins such as JNK and ERK. Moreover, AA treatment increased the phosphorylation of PI3K, Akt, GSK-3β and mTOR, suggesting that AA activated PI3K/Akt/mTOR signalling pathway, which might be the cause of neuroprotection offered by AA. The present findings provided more elaborate in vivo evidences to support the neuroprotective effect of AA on dopaminergic neurons of chronic Parkinson’s disease mouse model and the potential of AA to be developed as a possible new therapeutic target to treat PD.
KW - Apoptosis
KW - Asiatic acid
KW - MPTP/p
KW - NTFs
KW - PI3K/Akt
KW - Parkinson’s disease
UR - http://www.scopus.com/inward/record.url?scp=85011923794&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011923794&partnerID=8YFLogxK
U2 - 10.1007/s11064-017-2183-2
DO - 10.1007/s11064-017-2183-2
M3 - Article
C2 - 28181071
AN - SCOPUS:85011923794
SN - 0364-3190
VL - 42
SP - 1354
EP - 1365
JO - Neurochemical Research
JF - Neurochemical Research
IS - 5
ER -