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

Abstract

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.

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

“…It dissolves in methanol, ethanol, and water. Relevant literature on the nervous system demonstrated that C. asiatica and its triterpenes could be used to relieve a variety of neurological diseases, but the most researched are improve Alzheimer's disease (AD) (Song et al, 2018) and Parkinson's disease (Nataraj et al, 2017b) (Table 2). The pathogenesis of AD and Parkinson's disease involve neuroinflammatory activities (Gelders et al, 2018), oxidative stress (Jiang et al, 2016), mitochondrial dysfunction (Morais and De Strooper, 2010), and dysfunction in brain-derived neurotrophic factor (Mohammadi et al, 2018).…”

“…The concentration of this factor is reduced in the brain of patients with neurodegenerative diseases (Lima Giacobbo et al, 2019). C. asiatica extract, asiatic acid, and (Gopi and Arambakkam Janardhanam, 2017;Nataraj et al, 2017b;Chintapanti et al, 2018;Boondam et al, 2019). C. asiatica and its triterpenoids affect neurological diseases possibly through the mitogen-activated protein kinase (MAPK) signaling pathway, phosphotidylinositol 3 kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR)signaling pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway ( Table 2).…”

Traditional Herbal Medicines Against CNS Disorders from Bangladesh

“…Parkinson's disease [47] Citrus grandis Alzheimer's disease [73,78,80,290] cholinesterase, and to directly or allosterically bind to the GABAergic system; all with a relation to disorders like anxiety, insomnia, convulsion, pain, and cognitive deficits [25].…”

Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer rsquo s disease

“…Krishnamurthy et al (14) reported that asiatic acid (AA), a tri-terepene of CA could transverse the blood-brain barrier and mitigated mitochondrial injury in a mouse model of focal cerebral ischemia. Many previous studies revealed that this compound was a potent protective agent for brain against various neurotoxins (15)(16)(17)(18)(19).…”