Systematic Review of Multitarget Natural Products and Phytochemicals for Neurodegenerative Disease Therapy and Therapeutic Potentials

Abstract

Background: Neurodegenerative diseases are severe and incurable health issues that affect millions of people. Phytochemicals are being increasingly studied, for their multitarget effects. Aim: The objective is to examine research studies on multitarget natural products and phytochemicals for neurodegenerative diseases. Methods: This systematic review was conducted in accordance with the 2020 PRISMA guidelines. Searches from PubMed, Scopus, and Web of Science databases was conducted for original research studies published from the year 2020 to 2026. Included studies demonstrated evidence of multitarget action from in vitro or in vivo based studies. Results: The review showed that there is solid evidence for mulberroside A (a compound derived from mulberry), hesperetin and hesperidin (which are derived from citrus), extracts from Khaya grandifoliola, safflower yellow, alpha-terpinyl acetate (a compound derived from cardamom), and extracts from Atractylodes macrocephala. These compounds act on different mechanisms. They target harmful proteins (Aβ, tau, α-syn), reduce inflammation and oxidative damage. They also activate brain protective factors (PI3K/AKT, CREB/BDNF) and repair cholinergic function. In animal models, these compounds enhanced cognitive function, reduced neurodegenerative cell loss, diminished misfolded proteins, and reduced inflammation. Conclusion: There is evidence from the early stages of research that multitarget natural products could be a valuable means to combat AD and PD. In order to translate these compounds from plants into clinically viable products, there must be considerable effort directed toward the development of more effective targeting systems, such as the use of nanoparticles, along with the initiation of clinically-based studies.