Curr Neurovasc Res. 2026 Jun 18. doi: 10.2174/0115672026450208260330055837. Online ahead of print.

ABSTRACT

INTRODUCTION: Neurodegenerative diseases, notably Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), represent a significant and growing global health burden, characterized by progressive cognitive and motor dysfunction. Despite advances in understanding their multifactorial pathogenesis, current pharmacotherapies primarily provide symptomatic relief and fail to modify disease progression. This review critically evaluates the emerging role of bioactive phytocompounds as multi-target neuroprotective agents in the management of AD and PD, emphasizing mechanistic insights and translational challenges.

METHODS: A comprehensive literature search was conducted in PubMed, Scopus, and ScienceDirect, focusing on both preclinical and clinical studies that investigated the neuroprotective potential of key phytoconstituents, including luteolin, catechin, apigenin, and quercetin, derived from botanicals such as Commiphora wightii (Guggul), Curcuma longa, and Salvia officinalis.

RESULTS: Accumulating evidence demonstrates that these phytoconstituents exert potent antioxidant, anti-inflammatory, anti-amyloidogenic, and anti-apoptotic effects. Mechanistically, they modulate critical signalling pathways implicated in neurodegeneration, including attenuation of oxidative stress, suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-6), mitochondrial stabilization, inhibition of acetylcholinesterase activity, and prevention of amyloid-β aggregation. Their pleiotropic actions position them as promising adjuncts or alternatives to current mono-targeted therapies. However, clinical translation remains constrained by poor bioavailability, lack of standardisation, and limited pharmacokinetic profiling.

DISCUSSION: Phytocompounds show pleiotropic mechanisms (antioxidant, anti-inflammatory, anti-amyloidogenic) but clinical translation is limited by pharmacokinetic and standardisation barriers; novel delivery systems and rigorous clinical trials are required.

CONCLUSION: Phytocompounds represent a compelling, multi-target strategy for AD and PD management, yet significant barriers to clinical application persist. Future research should focus on the development of advanced drug delivery platforms (e.g., nanoformulations), robust clinical trials, and standardized phytopharmaceutical preparations to validate efficacy and safety. Integrative therapeutic frameworks combining phytochemicals with existing pharmacotherapies may offer a viable path toward disease modification in neurodegeneration.

PMID:42316568 | DOI:10.2174/0115672026450208260330055837