Functional profiling of Nardostachysin against Alzheimer’s Disease via integrated chromatographic and in silico methods.

Abstract

Background

Alzheimer disease (AD) is a well-known brain disorder affecting memory, and in later stages causing severe cognitive deficits. At present, few effective drugs are available in the clinic to manage symptoms, however none of these alter or reverse the progression in AD cases.  In this study, we have utilised nardostachysin, a terpenoid ester found in Nardostachys jatamansi, for its inhibition of AD pathological features.

Methods

We utilised the SwissTargetPrediction database to identify potential targets for nardostachysin, which we then cross-referenced with known Alzheimer's disease (AD) targets. The overlapping targets were used to create a protein-protein interaction network. Next, we focused on identifying how nardostachysin might target key AD-related pathologies, specifically tau and amyloid-beta (Aβ). To validate our findings, we performed molecular docking studies to assess the reliability and of these core target interactions.

Results

GC-MS analysis revealed presence of 15 different phytoconstituents. We identified 92 targets of nardostachysin, out of them 8 were found specific to AD. Bioinformatic analyses indicated that Aβ (PDB ID:2M4J), Tau (PDB ID:2MZ7), NTRK1 (PDB ID:4F01), MAPK10 (PDB ID:1MPU) CASP8 (PDB ID:2C2Z) have a good binding force with nardostachysin. The best docking score was found to be -9.24 for aβ.

Conclusions

In this study, nardostachysin was found to exert multichannel effects via modulating multiple AD related pathways.