Multi-Target Neuroprotection by Phytochemicals: Mechanisms, Clinical Evidence, and Translational Strategies for...

Neurological disorders (NDs) represent a significant and rapidly increasing global health problem, resulting in the progressive loss of neurons and cognitive decline. Current treatments are symptomatic and have major side effects. This review provides a detailed discussion on the roles and modes of action of the phytocompounds, their mechanistic pathways, and the challenges and opportunities, along with their clinical translation.

Relevant literature published in peer-reviewed journals was collected from databases including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using keywords related to phytochemicals, neuroprotection, oxidative stress, inflammation, and neurological disorders. Studies focusing on the mechanistic and therapeutic roles of plant-derived bioactive compounds were critically analyzed.

The application of different phytocompounds, including polyphenols, flavonoids, alkaloids, and terpenoids, is discussed. In addition, the roles and modes of action of phytocompounds such as curcumin, resveratrol, and epigallocatechin gallate (EGCG) have been discussed in relation to oxidative stress, inflammation, and protein aggregation. Their therapeutic actions are mediated via key mechanistic pathways, such as NF-κB inhibition, Nrf2/ARE activation, anti- apoptotic effects, neurotransmitter regulation, and chelation of redox-active metals.

Emerging evidence suggests that phytochemicals may mitigate oxidative stress, neuroinflammation, and neuronal damage associated with NDs. However, variability in phytochemical composition and insufficient clinical validation remain major concerns. Phytochemicals possess multi-target neuroprotective activities and may serve as promising therapeutic candidates for NDs. Challenges and Future Directions: The existing limitations, such as poor bioavailability, lack of standardization, and regulatory barriers, prevent clinical translation. The recent advances, including nanocarrier-based delivery of plant-derived drugs, artificial intelligence-driven phytocompound modelling, and pharmacogenomics-based personalized therapy, have been discussed.

Phytochemicals hold significant promise for neurotherapeutics. Nevertheless, their clinical application in several NDs requires advances in targeted drug delivery systems, precision medicine, standardized formulations, and robust mechanistic and clinical studies.