Discovery of Molecular Networks of Neuroprotection Conferred by Brahmi Extract in Aβ42-Induced Toxicity Model of Drosophila melanogaster Using a Quantitative Proteomic Approach

Accumulation of A beta(42) peptides forming plaque in various regions of the brain is a hallmark of Alzheimer's disease (AD) progression. However, to date, there is no effective management strategy reported for attenuation of A beta(42)-induced toxicity in the early stages of the disease. Alternate medicinal systems such as Ayurveda in the past few decades show promising results in the management of neuronal complications. Medhya Rasayana such as Brahmi is known for its neuroprotective properties via resolving memory-related issues, while the underlying molecular mechanism of the same remains unclear. In the present study, we aimed to understand the neuroprotective effects of the aqueous extract of Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) against the A beta(42) expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identified > 90% of differentially expressed proteins from A beta(42) expressing D. melanogaster were either restored to their original expression pattern or showed no change in expression pattern upon receiving either Brahmi extract treatment. The Brahmi restored proteins were part of neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also validated by negative geotaxis behavioral analysis suggesting its protective role against behavioral deficits exerted by A beta(42) toxicity. We believe that these discoveries will provide a platform for developing novel therapeutics for AD management by deciphering molecular targets of neuroprotection conferred by an aqueous extract of Bacopa monnieri or Centella asiatica.

Automated summary

Accumulation of A beta(42) peptides forming plaque in various regions of the brain is a characteristic of Alzheimer's disease progression. However, there is currently no effective management strategy for attenuating the early-stage toxicity induced by A beta(42). This study investigated the neuroprotective effects of aqueous extracts from Bacopa monnieri and Centella asiatica (both commonly known as Brahmi) using a Drosophila melanogaster model. Through quantitative proteomics analysis, the study found that the Brahmi extract restored the expression of a significant portion of differentially expressed proteins in A beta(42)-expressing flies, which are involved in neuronal pathways associated with cell cycle re-entry, apoptosis, and mitochondrial dynamics. The neuroprotective effect of Brahmi was also confirmed by negative geotaxis behavioral analysis. These findings provide a platform for developing novel therapies for Alzheimer's disease by elucidating the molecular targets of neuroprotection conferred by the aqueous extracts of Bacopa monnieri or Centella asiatica.