A Comprehensive Analysis of Extraction Methods, Phytochemical Characterization and Neuroprotective Potential of Curcumin

Abstract

Curcumin, a natural polyphenol derived from Curcuma longa, exhibits multi-targeted anti-inflammatory, antioxidant, and neuroprotective activities. This review aims to evaluate its extraction methodologies, synthetic pathways, and neuroprotective potential across preclinical and clinical paradigms, while addressing bioavailability barriers and commercial adulteration. In cellular models (BV-2, U87), curcumin inhibits TLR4/MyD88/NF-κB and NLRP3 inflammasome signaling, resulting in the downregulation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and enzymes (COX-2, iNOS), while simultaneously activating Nrf2/ARE antioxidant pathways. Moreover, it facilitates the polarization of neuroprotective M2 microglia. In animal models of ischemic stroke, traumatic brain injury, and Parkinson’s disease, curcumin reduces neuroinflammation, protects dopaminergic neurons, and maintains the integrity of the blood–brain barrier. Advanced nanocarriers such as PLGA nanoparticles, exosomes, and lipid complexes bypass rapid hepatic metabolism, thereby increasing brain bioavailability. Clinical data demonstrate that bioavailable formulations (Theracurmin, Longvida, CurQfen) could improve memory function and reduce cerebral amyloid and tau deposits in subjects without dementia and with mild cognitive impairment. Conversely, the use of unformulated curcumin results in inconsistent findings in trials for Alzheimer’s and Parkinson’s diseases owing to its poor systemic absorption. In conclusion, Curcumin might represent a promising multitarget neuroprotective agent; however, addressing pharmacokinetic limitations via bioavailable delivery systems and implementing rigorous quality control to prevent commercial adulteration are essential for effective clinical application.