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: The Role of MAPK, PI3K-Akt-GSK3β and mTOR Signalling Pathways.
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.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamilnadu, 608002, India.
Jagatheesan
J
Nataraj
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamilnadu, 608002, India. mani_pdresearchlab@rediffmail.com.
Thamilarasan
T
Manivasagam
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamilnadu, 608002, India.
Arokiasamy
A
Justin Thenmozhi
Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman.|Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman.|Food and Brain Research Foundation, Chennai, Tamil Nadu, 600094, India.
Musthafa Mohamed
MM
Essa
D000818:Animals; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011339:Probenecid / Q000633:toxicity*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016896:Treatment Outcome
D000071679:Glycogen Synthase Kinase 3 beta; D020929:Mitogen-Activated Protein Kinase Kinases; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011339:Probenecid; D058570:TOR Serine-Threonine Kinases; C017032:asiatic acid; C546843:mTOR protein, mouse
Apoptosis; Asiatic acid; MPTP/p; NTFs; PI3K/Akt; Parkinson’s disease