Simulated Digestion and Fermentation of Polyphenols From <i>Sargassum wightii</i> Acts as Potential Modulator of Alzheimer's Disease

The human gut microbiota regulates various aspects of Alzheimer's disease (AD) pathophysiology, influencing neuroinflammation and metabolic homeostasis. Dietary polyphenols, specifically phlorotannins from brown macroalgae, are known to mitigate AD's pathological effects due to their ability to pass through the blood-brain barrier. Marine polyphenols extracted from Sargassum wightii were processed through simulated gastrointestinal digestion and in vitro fermentation. Characterization was performed using ultraviolet (UV), Fourier transform infrared spectroscopy (FTIR), HPLC, and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) both before and after biotransformation. We evaluated their metal chelation capacity (Cu²⁺ and Fe²⁺) and acetylcholinesterase (AChE) inhibitory activity using colorimetric assays. Additionally, the antioxidant capacity of the polyphenol extract was evaluated before and upon fermentation using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant potential (FRAP) assays. The extraction yield of polyphenols from S. wightii was 2.67 ± 0.27 mg PGE/g of macroalgae. In vitro biotransformation of these polyphenols resulted in the formation of various low-molecular weight (LMW) compounds with enhanced metal chelation and AChE inhibition activities. Additionally, a substantial rise in antioxidant activity was observed postbiotransformation. S. wightii polyphenols become more effective after biotransformation, with enhanced bioactive properties and promising for use in diets to prevent and manage AD.