- Review
Role of Main Red Seaweed Bioactive Compounds in Modulating Redox Imbalance and Cholinergic Dysfunction: Insights from In Vitro Assays
- João Ferreira,
- Mário Pacheco and
- Isabel Gaivão
- + 1 author
Oxidative and nitrosative stress are key contributors to the development and progression of chronic inflammatory disorders, cancer and neurodegenerative diseases (viz., Alzheimer’s disease). Cholinergic dysfunction is a major hallmark of Alzheimer’s disease and is closely associated with these processes. Red seaweeds are rich in bioactive compounds that have been increasingly investigated for their potential to modulate these processes. This review aims to examine the role of major red seaweed-derived metabolites in regulating redox imbalance, immunomodulatory capacity and acetylcholinesterase activity, with emphasis on in vitro studies. An analysis of peer-reviewed literature was conducted, focusing on chemical, biochemical and cell-based assays. Studies assessed antioxidant activity, anti-inflammatory and immunostimulatory effects, and acetylcholinesterase inhibition of isolated compounds/fractions of red seaweed using established methods, including radical scavenging assays, Griess-based nitrite assay and enzyme inhibition assays. Sulfated polysaccharides, oligosaccharides, mycosporine-like amino acids (MAAs), phycoerythrin, bromophenols, phlorotannin and terpenoid-derived metabolites demonstrated antioxidant capacity through radical scavenging, metal chelation and modulation of endogenous antioxidants. They also modulated inflammatory mediators, including nitric oxide and pro-inflammatory cytokines, and inhibited acetylcholinesterase (AChE) activity. In vitro evidence supports red seaweed-derived compounds as promising modulators of redox homeostasis, inflammation and cholinergic function, highlighting their relevance as functional food ingredients, while underscoring the need for in vivo and clinical validation.
7 February 2026
![Impact of red seaweed-derived MAAs on redox balance and disease risk. The scheme provides a simplified representation of the complex processes and mediators involved. Environmental stressors include α-particles emitted during radon (Rn) decay and Escherichia coli. Mitochondria, through electron transport chain (ETC), generate reactive oxygen species (ROS) as they reduce O2 to H2O while producing energy in the form of ATP [21,22]. Although mitochondria are a major source, ROS are also produced in peroxisomes and by cytoplasmatic enzymes like NOX. Environmental stressors further exacerbate ROS formation. Key ROS include the superoxide radical (O2•−), hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). The latter is formed through the Haber–Weiss reaction (interaction of O2•− with H2O2) and the Fenton reaction mediated by heavy metals such as Fe2+ [23,24]. When endogenous enzymatic (e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPXs)) and non-enzymatic antioxidants (e.g., glutathione (GSH)) are supported with the neutralizing capacity of dietary antioxidants like MAAs, the capability of the organism to prevent oxidative stress increases [21,25,26]. As ROS and environmental stressors activate macrophages though the nuclear factor kappa B (NF-κB) signaling pathway, inflammation occurs [27]. NF-κB upregulates inducible nitric oxide synthase (iNOS), catalyzing the conversion of L-arginine into L-citrulline and releasing nitric oxide (NO). This process generates further reactive nitrogen species (RNS), such as peroxynitrite (ONOO−). Simultaneously, pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are secreted [6,27]. Macrophages also contribute to ROS production via NOX during respiratory bursts [20]. However, the broad arsenal of antioxidants can neutralize excessive levels of ROS and RNS through antioxidant and anti-inflammatory actions, thereby preventing chronic inflammation and the intertwined effects of oxidative and nitrosative stress, which would otherwise reinforce each other in a vicious cycle, leading to progressive damage to biomolecules [20,27,28,29,30]. Consequently, these compounds may ultimately contribute to a reduced risk of associated disease development and/or progression [21]. Abbreviations: ETC, electron transport chain; NOX, nicotinamide adenine dinucleotide phosphate oxidases; ATP, adenosine triphosphate; ROS, reactive oxygen species; O2•−, superoxide radical; H2O2, hydrogen peroxide; •OH, hydroxyl radical; SOD, superoxide dismutase; CAT, catalase; GPXs, glutathione peroxidases; MAAs, mycosporine-like amino acids; GSH, glutathione; NF-κB, nuclear factor kappa B; iNOS, inducible nitric oxide synthase; NO, nitric oxide; RNS, reactive nitrogen species; ONOO−, peroxynitrite; TNF-α, tumor necrosis factor-alpha; IL-6, interleukin-6.](https://mdpi-res.com/cdn-cgi/image/w=470,h=317/https://mdpi-res.com/cimb/cimb-48-00190/article_deploy/html/images/cimb-48-00190-g001-550.jpg)
