Table 2.

Summary of fucoxanthin’s biological activities and its beneficial mechanisms.

Bioactivities	Mechanisms/Benefits	References
Antioxidant	High antioxidant activities detected by several antioxidant assays; DPPH, FRAP and ABTS Suppress the generation of reactive oxygen species (ROS), nitric oxide (NO), and lipid peroxidation in HaCaT cells, ARPE-19 cells, and RAW 264.7 macrophage cells and human skin melanoma (A375) cells Modulate Nrf2/ARE, ERK/p38, PI3 K/Akt, and Sirt1 signalling pathways Alter the ROS, glutathione (GSH), glutathione S-transferase (GST), catalases, HO-1, NQO1, and apoptosis-related protein production	[26,38,106,107,108,109,110,111,112,113,114,118,119,120,121,204,205]
Anti-inflammatory	Inhibit prostaglandin (PGE2) and NO production by downregulation of COX-2 and iNOS enzymes expression, respectively Prevent degradation of IκB-α phosphorylation and reduce ERK1/2, p38, and JNK MAPKs phosphorylation Attenuate TNF-α, MCP-1, IL-1β, and IL-6 production Photo-protective effects; ○ Downregulate inflammasome components ASC, caspase-1, NLRP3, and IL-1β ○ Prevent UVB-induced skin erythema and epidermal hyperplasia ○ Reduce the myeloperoxidase (MPO) activity, skin oedema, UVB-induced erythema and HO-1 protein upregulation Inhibit Th17 cell development and stimulate Foxp3+ Treg cell differentiation Improve the intestinal immune function and epithelial barrier against the lipopolysaccharide effect	[108,110,111,123,124,125,126]
Anti-obesity	Stimulate mitochondrial uncoupling protein 1 (UCP1) and promote β-oxidation Attenuate the leptin expression and increase adiponectin levels Inhibit pancreatic lipases Inhibit the glycerol-3-phosphate dehydrogenase action and downregulate peroxisome proliferator-activated receptor γ (PPARγ) Reduce HbA1 c and glycated albumin levels Attenuate body and WAT weight and prevent excessive fat, lipid formation and adipocyte differentiation Decrease serum triglycerides level, plasma aminotransferase enzymes level, and blood pressure level Increase resting energy expenditure (REE) Downregulate mRNA levels of lipolysis-related genes (Lipe and Plin1), fatty acid uptake-related gene (Cd36), lipogenesis-related genes (Srebf1), and lipoprotein lipase coding (Lpl) Upregulate of the key transcriptional regulators (PPARγ, C/EBPα, and SREBP1 c) expression, transcription factors Regulate the adipogenic gene expression and a marker of adipocyte differentiation (aP2) Reduce PPAR, C/EBP, and SREBP1 c levels which inhibit IRS-1 phosphorylation Modulate SIRT-1 protein expression, AMPK, and FoxO pathways	[90,123,128,129,130,131,133,134,136,137,138,139,142,143]
Anti-diabetic	Reduce concentrations of plasma insulin, blood glucose, blood HbA1 C, and resistin levels Inhibit macrophage infiltration in both perigonadal and mesenteric WAT Decrease MCP-1 and TNF-α mRNA expression Attenuate overexpression of IL-6 mRNA and IL-6 generation Increase plasminogen activator inhibitor-1 (PAI-1) level and lessen expression levels of PAI-1 mRNA Decrease co-culture cells of 3 T3-L1 adipocyte and RAW264.7 macrophage cells Increase GLUT4 expression; elevation in translocation of GLUT4 to plasma membranes and improved EDL’s muscle translocation Increase the expression of IR mRNA by activating phosphorylation of Akt Upregulate PGC-1 α expression levels Stimulate serum adiponectin levels and decrease serum insulin levels Promote mRNA expression of the transcription factor peroxisome proliferator-activated receptor (PPAR) Inhibit the action of α -amylase hydrolyses oligosaccharides and α-glucosidase	[123,130,132,149,150,151,152,155,156,157,186]
Anti-cancer	Decrease numerous cancer cell viability Suppress the cell cycle in G0/G1, S, and/or G2/M phase depending on the cancer cell types Modulate several genes and protein expression, involving Mcl-1, STAT 3, p-STAT3, survivin, Bcl-2, Bcl-x, cIAP-2, XIAP, c-Myc, cyclin-dependent kinases (CDKs), and cyclin Induce apoptosis by altering several pathways; JAK/STAT signalling pathway, PI3 K/Akt/NF-κB signalling, and abruption of mortalin–p53 complex, and caspase activation Suppress fibroblast growth factor 2 (FGF-2) mRNA expression, receptor (FGFR-1), and trans-activation factor (EGR-1) Downregulates the phosphorylation of FGF-2-mediated intracellular signalling proteins (ERK1/2 and Akt) Reduce cells’ expression of PPAR and activation of Akt and increase the expression of integrin 1	[112,163,164,165,166,167,168,169,170,171,172,176]
Neuroprotective	Activate PI3 K/Akt cascade and inhibit ERK pathway Reduce the formation of Aβ plaques Suppress MAPK phosphorylation pathway Reverse the rise of acetylcholinesterase (AChE) activity Reduce choline acetyltransferase (ChAT) activity in the hippocampus and cortex Stimulate Nrf2- ARE and Nrf2-autophagy pathways and Nrf2/HO-1 signalling Exhibit mixed-type inhibition against BACE1; interact with BACE1 residues, Gly11 and Ala127	[113,149,180,181,182,183,184,185,186,188]
Antifibrotic	Attenuate the expression/production of α-smooth muscle actin (α-SMA), type 1 collagen (Col-1), fibronectin, and IL-6 Suppress MAPK phosphorylation, PI3 K/Akt pathway, Akt/SP-1 pathway, and Smad2/Smad3 pathway	[191,192]
Antitubercular	Suppress arylamine-N-acetyltransferase (TBNAT) and UDP-galactopyranose mutase (UGM)	[193]
Kidney protection	Upregulate Na+/H+ exchanger isoform 1 (NHE1) expression in renal tubules Inhibit renal fibrosis, reduced serum creatinine level, activated Akt, and inhibited H2 O2-induced apoptosis	[198,199,200,201]
Liver protection	Reduce liver weight gain, hepatic lipid oxidation, hepatic fat accumulation and mRNA expression levels of inflammation, and infiltration-related genes Suppress mRNA expression of lipogenesis-related genes, cholesterol esterification, lipid droplet accumulation, and induced CPT1 A mRNA level (β-oxidation related gene) Generate SREBP expression and reducing the liver’s cholesterol uptake through downregulation of SR-B1 and LDLR Accelerate omega-6 PUFA and omega-3 PUFA promotion to arachidonic acid (AA) and docosahexaenoic acid (DHA)	[111,202,203,206]