TABLE 3.

Therapeutic effect and toxicity studies of fucoxanthin.

Activity(s)	Models	Results	Mechanism of action	References
Anti-inflammation	RAW 264.7 macrophages	Inhibitory effects on inflammatory cytokines and mediators	Inhibition of nuclear factor-κB gene activation and phosphorylation of mitogen-activated protein kinases	Heo et al., 2012
	Mast cells	Suppression of mast cell degranulation in vivo	Suppression of antigen-induced aggregation of high-affinity IgE receptor and activation of degranulating signals of mast cells	Tan and Hou, 2014
Anti-obesity	Wistar rats and KK-Ay mice	A reduction of abdominal white adipose tissue weights in subjects	Inhibition of fat absorption and decreased serum triglyceride level by induction of uncoupling protein-1 (UCP-1)	Maeda et al., 2007
Anti-diabetic	Diabetic/obese mice	Fucoxanthin decreased the blood glucose and plasma insulin levels thereby improving alterations in lipid metabolism and insulin resistance induced by a high-fat diet via reduction of visceral fat mass, hyperinsulinemia, hepatic glucose production, and hepatic lipogenesis	Via downregulation of adipokines like tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-6 and, plasminogen activator inhibitor-1	Miyashita et al., 2012
Anti-cancer	MCF-7 breast cancer cell line	Chaetoceros calcitrans extracts were able to induce apoptosis at a concentration as low as 3 ppm	Fucoxanthin increased the expression of apoptotic genes, resulting in an increase in BAX/Bcl-2 ratio and activation of caspase 7 mRNA expression	Ebrahimi Nigjeh et al., 2013
	HepG2 cancer cell line	Chaetoceros calcitrans extracts induced cytotoxicity to HepG2 cells following concentration and time-dependent pattern	Modulation of numerous genes involved in cell signaling (AKT1, ERK1/2, and JNK), apoptosis (BAX, BID, Bcl-2, APAF, and CYCS), and oxidative stress (SOD1, SOD2, and CAT)	Foo et al., 2019
	BNL CL.2 transformed murine liver cells	Fucoxanthin acted as a cell signaling inhibitor at 12 h incubation (5 μM) of Undaria pinnatifida extracts	Fucoxanthin activated the Nrf2/ARE pathway by increasing the expressions of HO-1 and NQO-1 expression primarily through the ERK/P38 pathway	Liu et al., 2011
Anti-aging	Topical application on HOS: HR-1 hairless mice	Suppression of UVB-induced wrinkle formation	Fucoxanthin prevents skin photoaging via antioxidant and antiangiogenic effects	Urikura et al., 2011
Toxicity and safety evaluation	Single and repeated oral dose toxicity studies	No fatalities or abnormalities reported in both studies	Low toxicity and safe for consumption. Normal histology and no abnormal changes in liver, kidney, spleen, and gonadal tissues	Beppu et al., 2009
Multiple drug resistance (MDR)	Caco-2 and CEM/ADR5000 cells	Fucoxanthin exhibited a chemosensitizers role to alleviate MDR	By acting as competitive inhibitors of ATP-binding cassette (ABC)	Batista et al., 2012
Metabolism, bioavailability, and safety	Oral administration to mice	Results demonstrated dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A	This indicates that the bioavailability of fucoxanthin (and its metabolites) may be higher than that of other xanthophylls, at least of astaxanthin	Hashimoto et al., 2009
	13 groups of C57BL/6J mice	No toxicological effects were observed. Neither histological nor serum analyses revealed any heart, kidney, or liver toxicity induced by algae diets	Algae-rich diets were thus well accepted, well-tolerated and suitable for the maintenance of body weight and normal organ function	Neumann et al., 2018