Objective: Potential ‘Anti-parkinsonian’ activity of a tetrahydroisoquinoline (TIQ) molecule of traditional ‘Ayurveda’ medicine was tested in a preclinical MPTP mice model for Parkinson’s disease (PD).

Background: PD remains incurable and current treatments are laden with adverse side-effects. Amongst multiple factors, inflammation emerges as one of the prominent potentiators of dopaminergic neurodegeneration in PD. Indian ancient Ayurveda could be a treasure box for PD treatment. Substantial preclinical evidence is essential to validate the efficacy of ‘Anti-parkinsonian Ayurveda’ formulations. A novel Ayurveda molecule ‘TIQ’ might modulate inflammation to protect in MPTP parkinsonism.

Methods: Adult C57/BL6 mice injected with MPTP neurotoxin (18 mg/kg dose, 4 times at 2 h intervals) served as a reliable animal model for dopaminergic neurotoxicity and inflammatory activation in PD. TIQ was gavaged (200 mg/kg body weight, bi-daily) for 2 -7 days post MPTP and mice were sacrificed by cervical dislocation. Control mice were saline injected or fed with TIQ. Striatal dopamine levels were detected by HPLC electrochemistry. Striatal tyrosine hydroxylase (TH), NADPH oxidase-4 (NOX-4), hemeoxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) expressions were analyzed by western blot chemiluminescence procedure.

Results: TIQ MPTP mice showed significant recovery of striatal dopamine levels and tyrosine hydroxylase expression 7 days post-MPTP intoxication. MPTP-induced elevation in COX-2 and NOX-4 expression on day 2 post MPTP was significantly attenuated with TIQ treatment. TIQ MPTP mice further showed induction of HO-1 compared to MPTP mice.

Conclusions: Ayurvedic TIQ demonstrates its potency as an ‘Anti-parkinsonian’ molecule by protecting against dopaminergic neurotoxicity in mice. MPTP-induced upregulation of COX-2 -a classical inflammatory mediator, was significantly reduced with TIQ treatment. TIQ also attenuated MPTP-induced upregulation of NOX-4, a major oxidative marker and inflammation regulator. Further, a very potent antioxidant and anti-inflammatory molecule HO-1, was induced after TIQ treatment in the MPTP mice. Thus, TIQ may be a neuroprotective molecule in PD modulating neuroinflammatory oxidative mechanisms.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/tetrahydroisoquinoline-molecule-identified-in-traditional-ayurveda-medicine-modulates-inflammation-in-mptp-mice/