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Neuroprotective propensity of marmelosin against 6-OHDA-induced cognitive impairment and apoptosis via upregulation of PI3K/Akt pathway

E. Yadav (Allahabad, India)

Meeting: MDS Virtual Congress 2020

Abstract Number: 451

Keywords: Dopamine

Category: Parkinson's Disease: Cognitive functions

Objective: Current study was designed to explore the neuroprotective effect of marmelosin against apoptosis caused by 6-hydroxydopamine (6-OHDA) by upregulating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway.

Background: Deficit in dopamenergic neuron and neuro-inflammation are known as major pathological hallmark of Parkinson’s disease (PD). Marmelosin, a natural furanocoumarin bioactive constituent of Indian traditional medicinal plant, Aegle marmelos, has been clinically utilized for treatment of various neurodegenerative diseases as it possess strong antioxidant and anti-inflammatory activities.

Method: Twenty four rats were utilized for the study and they were treated unilaterally with 6-OHDA injection into the mid brain’s substantia nigra at a dose level of 5 μg/2 μL. Rats were randomly divided into four groups, Marmelosin (10, 20 and 40 mg/kg) and Control (Vehicle), and treated with their respective treatment for 30 consecutive days. The severity of damaging effects induced by 6-OHDA was measured by behavioral tests (open field test and locomotor activity) performance. Evaluation of underlying mechanism concerning PI3K/Akt upregulating pathway was undertaken via Western blotting method and immunohistochemical detection.

Results: Marmelosin (20 and 40 mg/kg; p<0.05, p<0.01, respectively) ameliorated the damaging effects induced by 6-OHDA by significant improvement of cognitive function as well as elevation in level of dopaminergic neurons and p-Akt Ser473, PI3K-110α expression and pro-caspase-3 as compared with control group. Additionally, a significant reduction in the concentration of activated caspase-3 and ratio of Bax/Bcl-2 was observed in marmelosin (20 and 40 mg/kg) administered group.

Conclusion: The results suggest that marmelosin significantly reversed 6-OHDA-induced cognitive impairment and apoptosis by regulating the PI3K/Akt pathway. Thus, it could be utilized as a promising neuroprotective agent for treatment of PD.

To cite this abstract in AMA style:

E. Yadav. Neuroprotective propensity of marmelosin against 6-OHDA-induced cognitive impairment and apoptosis via upregulation of PI3K/Akt pathway [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/neuroprotective-propensity-of-marmelosin-against-6-ohda-induced-cognitive-impairment-and-apoptosis-via-upregulation-of-pi3k-akt-pathway/. Accessed June 15, 2025.
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