Prasad Thakurdesai
Indus Biotech Private Limited, India
Title: Therapeutic efficacy of trigonelline-based standardized extract of fenugreek seeds on Levodopa induced dyskinesia in 6-OHDA lesioned rat model of Parkinson’s disease
Biography
Biography: Prasad Thakurdesai
Abstract
The objective of the present work is to explore the therapeutic efficacy and possible mechanism of trigonelline-based standardized extract of fenugreek seeds (IBHB) on L-dopa induced dyskinesia (LID) in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson’s disease (PD). The motor symptoms of PD and LID were induced in rats with single unilateral intracerebroventricular injections of 6-OHDA in the striatum area of brain (PD) on day-0 and daily treatment with L-DOPA + Benserazide from Day-29 to Day-56 (LID) respectively. Rats were then randomly divided into groups and administrated with subacute treatment either with vehicle, amantadine (40 mg/kg, i.p.) or IBHB (15, 30 or 60 mg/kg, oral) for next 45 days and then sacrificed for collection of brain striatal samples for ex vivo experiments. Subacute treatment of IBHB showed dose-dependent reduction in behavioral parameter scores (abnormal involuntary movements (AIMS), grid test, catalepsy bar test, Forelimb adjusting steps) as compared to vehicle treated LID group. During ex vivo experiments, IBHB showed restoration of upregulated neurotransmission (serotonin and dopamine turnover and 3-O-Methyldopa levels), immunoreactivity (FosB and 5HT2c), and mRNA expressions (c-FOS, CO-1, Homer-1, Parkin, Pdyn, Penk and PINK1) and downregulated mitochondrial respiratory chain complexes activity and mRNA expression of JunD in striatum as compared to vehicle treated LID control rats. In conclusion, subacute treatment of IBHB showed promising therapeutic anti-dyskinetic efficacy in preclinical model of LID in rats and supports the utility for the improved treatment of LID and PD.
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