Abstract
Gracilaria species, a widely distributed genus of red macroalgae, have gathered significant attention for their diverse medical applications attributable to their bioactive sulphated polysaccharides (SPs). This review examines the global narrative of various Gracilaria SP applications in terms of their therapeutic potential and mechanistic insights into the use of these SPs against a range of medical conditions, including cancer, inflammation, neurodegenerative disorders, diabetes, and immune dysfunctions. SPs extracted from G. lemaneiformis and G. fisheri have demonstrated potent anti-tumour activities by inducing apoptosis through various mechanisms, including the upregulation of CD8(+) T cells and IL-2, inhibition of EGFR/MAPK/ERK signalling pathways, and activation of the Fas/FasL pathway. Selenium nanoparticles (SeNPs) conjugated with SPs further enhanced the targeted delivery and efficacy of these SPs against glioblastoma by the downregulation of ROS followed by the activation of p53, MAPK, and AKT pathways. The anti-inflammatory properties of SPs are evidenced by key suppressive inflammatory markers like NO, TNF-α, IL-1β, and IL-6 in mutant rodent models. SPs from G. cornea and G. birdiae effectively reduce neutrophil migration and vascular permeability, offering potential treatments for acute inflammation and conditions such as colitis by modulating pathways involving COX-2 and NF-κB. Neuroprotective effects by SPs (from G. cornea and G. gracili) studied in 6-OHDA-induced rats, which mitigate oxidative stress and enhance neuronal cell viability, facilitate the management of neurodegenerative diseases like Parkinson's and Alzheimer's. Regarding the hypoglycaemic effect, SPs from G. lemaneiformis exhibit a glucose-modulating response by improving insulin regulation, inhibiting α-amylase activity, repairing pancreatic β-cells, and modulating lipid metabolism. Moreover, immunomodulatory activities of Gracilaria-derived SPs include the stimulation of macrophages, T-cell proliferation, and cytokine production, underscoring their potential as functional food and immunotherapeutic agents. Recently, Gracilaria-derived SPs have been found to modulate gut microbiota, promote SCFA production, and enhance gut microbials, suggesting their potential as prebiotic agents (G. rubra and G. lemaneiformis). This review highlights the multifaceted medical applications of Gracilaria sulphated polysaccharides, providing detailed mechanistic insights and suggesting avenues for future clinical translation and therapeutic innovations.