Phytochemical-based Neuroprotection and In-silico Docking-driven Identification of Active Natural Compounds to Combat Neuropathy.

INTRODUCTION

Neuropathic pain, a devastating neurological disorder attributed to impairment or malfunctioning of the somatosensory system, affecting 10% of the world population. Current therapy emphasizes symptomatic management, featuring high-order side effects. Phytocompounds as neuroprotective agents are of growing interest, and can be screened using structure-based docking, and can act upon a variety of pathways with fewer adverse effects.

METHODS

A comprehensive literature survey was conducted covering studies published between 2000 and 2022 using scientific databases including PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. The neuroprotective potential of medicinal plants and their bioactive phytochemicals was screened using in silico experiments targeting neuropathy-related molecular targets, followed by the evaluation of in vitro and in vivo activities.

RESULTS

The studies showed that phytochemicals have multitarget neuroprotective activities, including antioxidant activity, modulation of neurotransmitter signaling, inhibition of inflammatory mediators, and modulation of neuropathic signaling ion channels. Several phytochemicals demonstrated notable binding affinities in docking studies, including icariin with NMDA receptors (-12.646 kcal/mol), aegeline with MAO-A (-10.06 kcal/mol) and MAO-B (-10.09 kcal/mol), and zerumbone with cannabinoid receptors CB1 (-7.80 kcal/mol) and CB2 (-9.40 kcal/mol). Other compounds, such as chlorogenic acid, myricetin, rutin, and piperine, also exhibited significant interactions with key neuropathic targets involved in neuroinflammation and pain signaling pathways.

DISCUSSION: Docking studies identified that icariin, aegeline, and zerumbone are predicted lead molecules because they can interact with targets of interest, including NMDA, MAO, and CB receptors.

CONCLUSION

Phytochemical neuroprotective drugs offer a promising approach to managing neuropathy. Integration of molecular docking approaches with experimental pharmacological studies provides a powerful strategy for identifying bioactive natural compounds with therapeutic potential. These findings support advancing phytochemicals as lead candidates for the development of safer, more effective treatments for neuropathy and neuropathic pain.