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

Abstract

Accumulation of Aβ 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 Aβ 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 (commonly known as Brahmi) against the Aβ 42 expressing model of the Drosophila melanogaster. By applying a quantitative proteomics approach, the study identi ed > 90% of differentially expressed proteins from Aβ 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 de cits exerted by Aβ 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.

Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis

“…These findings are due to restoring proteins related to mitochondrial dynamics, cycle re-entry, and apoptosis. The neuroprotective actions were also related to the protective role regarding behavioral impairments promoted by Aβ42 toxicity [142].…”

“…It was observed that BM restores proteins involved in neural pathways related to cell cycle regulation, programmed cell death (apoptosis), and the functioning of mitochondria [142]. The protective effect of mitophagy mediates the anti-senescence and antiapoptotic activities of BM; if mitophagy is inhibited, there will be no protection of astrocytes in mitochondrial apoptosis induced by ROS and aging of cells treated with BM.…”

Nootropic Herbs, Shrubs, and Trees as Potential Cognitive Enhancers

“…They are five-petaled, purple-blue, or white with darker veins. It is often confused with Centella asiatica (L.) Urban, as both these plants are known by the same Hindi name, brahmi, in many places in India [ 246 , 247 , 248 , 249 ].…”

Comparative metabolomics and network pharmacology analysis reveals shared neuroprotective mechanisms of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb

“…Furthermore, B. monnieri and C. asiatica extracts have been proven to improve learning, memory, behavior, and cognition [11,10,[12][13][14]. We recently demonstrated that B. monnieri and C. asiatica extracts showed neuroprotective activity in the Drosophila model of Alzheimer's disease [15]. Based on this literature, it may be possible that B. monnieri and C. asiatica may bring neuroprotection via similar mechanisms of action; however, they belong to distant botanical classes.…”