Introduction

Alzheimer’s disease has a complex etiology involving proteins like amyloid beta and tau. Tau has seen increasing interest in the past decade, and therapeutic strategies targeting it are being investigated. WHO has developed the TCIM Strategy to encourage evidence-based research in traditional medicine. Exploring this opportunity, we have dissected the molecular mechanisms of the neuroprotective activities of a widely used polyherbal formulation – Saraswat churna (SC).

Methods

SC aqueous extract preparation
Q-TOF-MS/MS
Network pharmacology
Molecular docking
Molecular Dynamics
Cell line investigations (SH-SY5Y model)

Results

Q-TOF-MS/MS analysis revealed around 723 compounds in SC.
The protein-protein network acquired from the STRING database shows genes involved in dementia and tau pathology interact with each other. Further, target prediction revealed the possible interactions between the genes and the compounds from SC. These interactions, when subjected to molecular docking and MD simulations, reveal important interactions with acetylcholine and GSK-3β.

Conclusions

The polyherbal formulation has multiple bioactive compounds, thereby providing a multi-target strategy of therapeutic intervention
This multiple target approach is validated in network pharmacology studies, which show one compound interacting with various disease targets.
Further, molecular docking and MD simulations show that this interaction with the disease targets is stronger and interacts with amino acids at important sites. This controls the inhibition of AChE and hyperphosphorylation of GSK-3β.
Moreover, it is exhibited in cell line models that SC is good at increasing cell viability and protecting synaptic networks after cholinergic damage.
A combination of SC and Donepezil shows synergistic neuroprotection.

Future perspectives

Gene and protein expression studies to elucidate the pathways involved.

References

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