Objective: Tetrahydroisoquinoline (TIQ) an identified alkaloid from ancient Indian ‘Ayurveda’ medicine for Parkinson’s disease (PD) was tested for neuroprotection in a cellular system and a preclinical mouse PD model.

Background: PD treatment remains symptomatic with disabling side-effects. Ayurveda describes treatment for ‘Kampavata’ or PD and novel herbal molecules might be neuroprotective.

Methods: Co-cultures of murine neuronal (Neuro2a), microglial (EOC20) and astrocytic (C8D30) cells were challenged with MPP+ a potent dopaminergic neurotoxin. TIQ (0.1-10 µM) incubated for 24 h post-MPP+ were subjected to MTT cell viability or Live Dead assays. Neuro2a cells, dbcAMP-differentiated to dopamine neurons were cultured in indirect contact with astrocytes and microglia through inserts. Mitochondrial superoxide radical accumulation in dopaminergic neurons was determined by MitoSOX dye flow cytometry. Adult C57/BL6 mice were acutely intoxicated with the MPTP parkinsonian neurotoxin (16 mg/kg dose, 4 times at 2 h intervals) and TIQ was gavaged (200 mg/kg body weight, bi-daily) for 7 days post MPTP intoxication. Control mice were PBS injected or fed with TIQ alone. Striatal dopamine levels on 7th day post-MPTP were measured by HPLC electrochemical detection. Striatal tyrosine hydroxylase (TH) enzyme expression was assayed by immunoblotting.

Results: In vitro, TIQ (10 µM) treatment significantly attenuated MPP+-induced loss of total cell viability. Live Dead Assay confirmed a significant (37%) increase in the number of live (Calcein AM-positive) differentiated neurons compared to MPP+ alone incubated for 24 h. Further, MPP+-induced mitochondrial accumulation of toxic superoxide radicals in dopamine neurons was significantly reduced (30%) by TIQ (10 µM). In vivo, TIQ ameliorated dopaminergic neurotoxicity in mice by causing a significant 16% increase in MPTP-induced striatal dopamine loss with 1.2-fold upregulation of the reduced expression of TH at the striatal terminals.

Conclusions: The anti-parkinsonian neuroprotective potential of TIQ is revealed in MPP+-exposed cell co-culture and in MPTP mice. TIQ protects through reduced toxic mitochondrial superoxide radicals, recovery of striatal dopamine levels and tyrosine hydroxylase expression. Molecular basis for TIQ’s dopaminergic neuroprotection could translate into therapeutic benefit in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-potency-of-tetrahydroisoquinoline-a-novel-ayurveda-molecule-in-experimental-parkinsons-disease/