Abstract
Dopaminergic neuroprotection is the main interest in designing novel therapeutics against Parkinson’s disease (PD). In the process of dopaminergic degeneration, mitochondrial dysfunctions and inflammation are significant. While the existing drugs provide symptomatic relief against PD, a therapy conferring total neuroprotection by targeting multiple degenerative pathways is still lacking. Garcinia morella is a common constituent of Ayurvedic medication and has been used for the treatment of inflammatory disorders. The present study investigates whether administration of G. morella fruit extract (GME) in MPTP mouse model of PD protects against dopaminergic neurodegeneration, including the underlying pathophysiologies, and reverses the motor behavioural abnormalities. Administration of GME prevented the loss of dopaminergic cell bodies in the substantia nigra and its terminals in the corpus striatum of PD mice. Subsequently, reversal of parkinsonian behavioural abnormalities, viz. akinesia, catalepsy, and rearing, was observed along with the recovery of striatal dopamine and its metabolites in the experimental model. Furthermore, reduced activity of the mitochondrial complex II in the nigrostriatal pathway of brain of the mice was restored after the administration of GME. Also, MPTP-induced enhanced activation of Glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) in the nigrostriatal pathway, which are the markers of inflammatory stress, were found to be ameliorated on GME treatment. Thus, our study presented a novel mode of dopaminergic neuroprotection by G. morella in PD by targeting the mitochondrial dysfunctions and neuroinflammation, which are considered to be intricately associated with the loss of dopaminergic neurons.
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Data availability
The datasets generated during and/or analysed during the current study are available from the first author (duttaankur56@gmail.com) and corresponding author on reasonable request.
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Funding
We acknowledge the support provided by the Department of Biotechnology, Government of India (BT/230/NE/TBP/2011 and BT/PR17127/NER/95/453/2015).
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The idea and concept of the proposed study were designed by MKM, RP and AB. In vivo experiments were carried out by BCP and AD. In vitro experiment was performed by AD and BCP. Data interpretation, statistical analysis and script writing were performed by AD and BCP. The manuscript was edited by BCP, MKM, SK, RR, JN and AB. Studies performed were critically evaluated by MKM, RP, AC, PB, SK, DK and AB.
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Dutta, A., Phukan, B.C., Roy, R. et al. Garcinia morella extract confers dopaminergic neuroprotection by mitigating mitochondrial dysfunctions and inflammation in mouse model of Parkinson’s disease. Metab Brain Dis 37, 1887–1900 (2022). https://doi.org/10.1007/s11011-022-01001-9
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DOI: https://doi.org/10.1007/s11011-022-01001-9