Table 1.

Summary on pharmacological effects, occurrence, effective dose, experimental model, cellular effects, potential pharmacological mechanism of algal metabolites.

Pharmacological Effects	Compound (Class)	Algal Source If Any)	Effective Concentration	Experimental Model (In Vivo/In Vitro)	Cellular Effects/Significant Findings	Signaling Pathways Involved	Pharmacological Markers	Reference
Antioxidant activity	Fucoxanthin (carotenoids)	Sargassum siliquastrum	50 and 100 μM	H2O2-induced cell damage in kidney fibroblast cells	Attenuates oxidative stress	n.d.	↓ROS level	[69]
	Fucoxanthin		5, 10, and 50 μM	H2O2 induced BV2 microglial cells	Antioxidation	Antioxidant pathway	↓ROS ↑SOD and GSH	[36]
	Fucosterol, 3,6,17-trihydroxy-stigmasta-4,7,24(28)-triene and 14,15,18,20-diepoxyturbinarin (sterols)	Pelvetia siliquosa	A seven day-dose regimen at 30 mg/kg/day before carbon tetrachloride (CCl4) administration	Rat model	Antioxidation	n.d.	↑SOD, CAT, and GPx	[71]
	Fucosterol	Eisenia bicyclis, brown alga	25, 50, 100, 200, and 400 μM	RAW 264.7 murine macrophages (t-BHP stimulated)	Protects against oxidative stress	n.d.	↓ROS generation	[72]
	Fucosterol	Ecklonia stolonifera and Eisenia bicyclis; Brown algae	25, 50, and 100 μM	tert-Butyl hydroperoxide- and tacrine-induced HepG2cell injury model	Antioxidation	n.d.	↓ROS generation ↑GSH level	[73]
	Fucosterol	Sargassum Binderi; brown alga	3.125, 6.25, 12.5, 25, 50, and 100 μg /mL	Particulate matter-induced injury and inflammation in A549 human lung epithelial cells	Attenuates oxidative stress		↓ROS level ↑SOD, CAT, and HO-1 in the cytosol, and NRF2 in the nucleus	[74].
	Glycoprotein	U. pinnatifida	SOD activity and Xox activity at a concentration of 5 mg/mL and 1 mg/mL, respectively	In vitro enzyme assay			↑SOD and↓Xox	[75]
	Sulfated oligosaccharides	Ulva lactuca and Enteromorpha prolifera; green algae	150 mg/kg·day	Aging model (male senescence-accelerated prone (SAMP8) and male senescence resistant (SAMR1) mice)	Antioxidantion	n.d.	↑GSH, SOD, CAT, telomerase levels, ↑Total antioxidant capacity, ↓MDA and AGEPs	[96]
Anti-inflammatory activity	Fucoxanthin		5, 10, and 50 μM	Aβ42-induced BV2 microglia cells	Anti-inflammation	MAPK pathway	↓iNOS, COX-2 ↓TNF-α, IL-6, IL-1β, PGE2 ↓JNK, ERK, and p38 MAPK phosphorylation	[36]
	Fucoxanthin	-		LPS-activated BV-2 microglia	Anti-inflammation and antioxidation	Akt/NF-κB and MAPKs/AP-1 pathways; PKA/CREB pathway	↓iNOS, COX-2, ↓TNF-α, IL-6, PGE2, NO, ROS ↓IL-6, TNF-α, iNOS, and COX-2 mRNA expression ↓Akt, NF-κB, ERK, p38 MAPK and AP-1 phosphorylation ↑Nrf2, HO-1 ↑PKA, CREB ↑BDNF	[70]
	Fucosterol	E. bicyclis; brown alga	5–20 μM for NO	RAW 264.7 murine macrophages (t-BHP 200 μM, LPS-1μM stimulated)	↓Inflammatory response	↓NF-κB pathway	↓NO production ↓iNOS and COX-2	[72]
	Fucosterol	U. pinnatifida	10, 25, or 50 μM	LPS-induced RAW 264.7 macrophages and THP-1 human monocyte cell line	↓Inflammatory response	↓NF-κB pathway	↓iNOS, TNF-α, and IL-6 ↓DNA binding ↓phosphorylation of NF-κB, MKK3/6 and MK2	[83]
	Fucosterol	Hizikia fusiformis	1–10 μM	CoCl2 induced hypoxia in keratinocytes	↓Inflammatory response	n.d.	↓IL-6, IL-1β and TNF-α ↓pPI3K and pAkt and HIF1-α accumulation	[82]
	Fucosterol	Panida. australis	0.004,0.2, and 10 μM	LPS or Aβ-induced BV2 (microglial) cells	Protects against LPS or Aβ-mediated neuroinflammation	n.d.	↓IL-6, IL-1β, TNF-α, NO, and PGE2	[85]
	Fucosterol	S. Binderi; brown alga	3.125, 6.25, 12.5, 25, 50, 100 μg/mL	Particulate matter-induced injury and inflammation in A549 human lung epithelial cells	↓Inflammatory response	n.d.	↓COX-2, PGE2, TNF-α and IL-6	[74]
	Dieckol (phlorotannin)	E. cava	50–300 µg/mL	LPS-stimulated murine BV2 microglia	Anti-inflammation and antioxidation	p-38 MAPK/ NF-κB pathway	↓NO and PGE2; ↓iNOS and COX-2; ↓IL-1β and TNF-α; ↓ROS	[86]
	Phloroglucinol, eckol, dieckol, 7-phloroeckol, phlorofucofuroeckol A and dioxinodehydroeckol (phlorotannin)	E. bicyclis; brown alga	5–20 μM for NO	LPS-stimulated RAW 264.7 murine macrophages	↓Inflammatory response	↓NF-κB pathway	↓NO production	[72]
	Phlorofucofuroeckol A	E. stolonifera	20 μM	LPS-activated BV2 and primary microglial cells	Anti-inflammation	NF-κB, JNKs, p38 MAPK, and Akt pathways	↓NO and PGE2; ↓iNOS and COX-2; ↓IL-1β, IL-6 and TNF-α; ↓NF-κB activation and IκB-α degradation ↓JNK, p38, and Akt	[87]
	Phlorofucofuroeckol B (phlorotannin)	E. stolonifera	10–40 µM	LPS-stimulated murine BV2 microglia	Anti-inflammation	IκB-α/NF-κB and Akt/ERK/JNK pathways	↓TNF-α, IL-1β and IL-6; ↓COX-2 and iNOS ↓NF-κB activation and IκB-α degradation ↓Akt, ERK, and JNK phosphorylation	[88]
	8,8’-bieckol (phlorotannin)	E. cava		LPS-stimulated primary macrophages and RAW 264.7 macrophages & LPS-induced septic mice	Anti-inflammation; Protects mice from endotoxin shock	NF-κB pathway	↓NO and PGE2; ↓iNOS mRNA and protein expression; ↓IL-6; ↓Transactivation of NF-κB and nuclear translocation of the NF-κB p65 subunit ↓ROS	[90]
	6,6′-bieckol (phlorotannin)	E. stolonifera		LPS-stimulated BV2 and murine primary microglial cells	Anti-inflammation	IκB-α/NF-κB and JNK/p38 MAPK/Akt pathways	↓COX-2 and iNOS; ↓NO and PGE2, ↓IL-6 ↓Transactivation of NF-κB and nuclear translocation of the NF-κB p65 subunit ↓Akt, JNK and p38 MAPK phosphorylation	[89]
	Fucoidan (sulfated polysaccharide)	Brown seaweed	25, 50, and 100 µg/mL	LPS-stimulated murine BV2 microglia	Anti-inflammation	NF-κB and JNK/p38 MAPK/Akt pathways	↓NO and PGE2; ↓COX-2, iNOS and MCP-1; ↓TNF-α and IL-1β; ↓NF-κB activation; ↓Akt, ERK, p38 MAPK and JNK phosphorylation	[92]
	Fucoidan	-	125 µg/mL	LPS-activated primary microglia	Anti-inflammation	n.d.	↓TNF-α and ROS	[93]
	κ-carrageenan oligosaccharides and desulfated derivatives	Red algae		LPS-activated microglia	Anti-inflammation	n.d.	↓TNF-α	[94]
	Sulfated oligosaccharides	U. lactuca and E. prolifera; green algae	150 mg/kg·day	Aging model (male senescence-accelerated prone (SAMP8) and male senescence resistant (SAMR1) mice)	↓Inflammatory response	n.d.	↓IFN-γ, TNF-α, and IL-6	[96]
	Alginate-derived oligosaccharide	Brown algae	50–500 µg/mL	LPS/Aβ-stimulated BV2 microglia	Anti-inflammation	TLR4/NF-κB signaling pathway	↓NO and PGE2; ↓COX-2 and iNOS; ↓TNF-α, IL-6 and IL-12; ↓TLR4; ↑NF-κB/p65 subunit translocation	[97]
	Seleno-polymannuronate	Brown algae	0.8 mg/mL	LPS-activated primary microglia and astrocytes; mouse model of acute inflammation	Anti-inflammation	NF-κB and MAPK signaling	↓NO and PGE2; ↓COX-2 and iNOS; ↓TNF-α, IL-1β and IL-6; ↑IκB-α, p65, p38, ERK and JNK phosphorylation	[98]
	Sargachromenol (plastoquinone)	Sargassum micracanthum	30.2 μM (IC50)	LPS-stimulated RAW 264.7 macrophages	Anti-inflammation	NF-κB signaling	↓NO and PGE2; ↓COX-2 and iNOS; ↑IκB-α	[99]
	Sargaquinoic acid (plastoquinone)	Sargassum siliquastrum		LPS-stimulated RAW 264.7 macrophages	Anti-inflammation	NF-κB signaling	↓NO; ↓iNOS; ↑IκB-α; ↓nuclear translocation of NF-κB; ↓JNK1/2 MAPK	[100]
	Floridoside (glycerol glycosides)	Laurencia undulate; red alga	50 μM	LPS-stimulated murine BV2 microglia	Anti-inflammation	MAPK Signaling	↓NO, ROS; ↓iNOS and COX-2; ↓p38 MAPK and ERK phosphorylation	[101]
	Glycoprotein	U. pinnatifida	COX-1 and COX-2 inhibition with IC50 values of 53.03 ± 1.03 μg/mL and 193.35 ± 3.08 μg/mL, respectively	LPS-stimulated RAW 264.7 macrophages	Anti-inflammation	n.d.	↓COX-1 and COX-2 ↓NO	[75]
	Caulerpin (bisindole alkaloid)	Caulerpa racemosa	100 µM/kg body wt	Capsaicin-induced ear edema and carrageenan-induced peritonitis	Inhibition of nociception	n.d.	n.d.	[130]
	Caulerpenyne (sesquiterpene)	C. prolifera and C. racemosa	5.1 μM	Lipoxygenase (LOX) enzyme activity assay	Inhibitory activity against LOX	-	Un-competitive type of inhibition	[131]
	Aquamin (multi-mineral complex)	Lithothamnion corallioides; red alga		LPS-stimulated, glial-enriched primary cultures of rat cortex	Anti-inflammation	n.d.	↓TNF-α and IL-1β	[132]
Anticholinesterase activity	Fucosterol and 24-hydroperoxy 24-vinylcholesterol	E. stolonifera	IC50 values of 421.72 ± 1.43, 176.46 ± 2.51 µM, respectively	In vitro enzymatic assay	↓BChE activity	-	Selective inhibition of BChE	[114]
	Fucosterol	Panida australis	inhibition against AChE (10.99–20.71%) and BChE (4.53–17.53%) with concentrations ≤ 56 μM,	In vitro enzymatic assay	↓AChE and BChE activities	-	Nonselective cholinesterase inhibition	[85]
	Fucosterol	Sargassum horridum	-	In vitro enzymatic assay	↓AChE activity	-	Non-competitive inhibition	[115]
	Fucoxanthin	-	IC50 value 1.97 mM	In vitro BChE activity assay	↓BChE activity		Mixed inhibition type	[116].
	Fucoxanthin	Brown seaweed	IC50 value of 81.2 μM	In vitro AChE activity assay; Molecular docking analysis	↓AChE activity	Fucoxanthin likely interacts with the peripheral anionic site within AChE	Non-competitive manner	[117]
	α-Bisabolol	Padina gymnospora	IC50 value < 10 μg/mL	In vitro enzymatic assay	↓AChE and BChE activity	-	-	[118]
	Glycoprotein	U. pinnatifida	AChE and BChE inhibitory activities with IC50 values of 63.56 ± 1.86 and 99.03 ± 4.64, respectively	In vitro enzymatic assay	↓AChE and BChE activity	-	-	[75]
	Phloroglucinol, dibenzo [1,4] dioxine-2,4,7,9-tetraol and eckol	Ecklonia maxima; Brown alga	IC50 value: 76.70 to 579.32 μM	In vitro AChE activity assay	↓AChE activity	-	-	[119]
	Dieckol and phlorofucofuroeckol	E. cava		Ethanol-intoxicated memory impairment in mice	↓AChE activity	n.d.	↑Acetylcholine	[120]
	Sargaquinoic acid and sargachromenol (plastoquinones)	Sargassum sagamianum	IC50 value for anti-AChE: 23.2 and 32.7 μM, respectively; IC50 value for anti-BChE of sargaquinoic acid 26 nm	In vitro ChE activity assay	Sargaquinoic acid shows potent inhibitory activity against BuChE and moderate inhibitory activity against AChE	-.	-	[121]
	(5E,10Z)-6,10,14-trimethylpentadeca-5,10-dien-2,12-dione and (5E,9E,13E)-6,10,14-trimethylpentadeca-5,9,13-trien-2,12-dione (Sesquiterpenes)	S. sagamianum	IC50 values of 65.0 and 48.0, and 34.0 and 23.0 μM, respectively	In vitro ChE activity assay	Moderate inhibitory activity against AChE and BuChE	-	-	[133]
Anti-amyloidogenic and aggregation inhibition activity	Fucoxanthin	E. stolonifera and U. pinnatifida			↓β-secretase activity; Binding energy (-7.0 kcal/mol)	-	mixed-type inhibition	[134]
	Fucoxanthin	-	0.1–30 μM		Suppresses the formation of Aβ1-42 fibrils and Aβ1–42 oligomers, and inhibits Aβ aggregation	-	-	[135]
	Fucoxanthin	-	2 μM	ThT assay	Inhibits Aβ1-42 fibril and aggregate formation	-	-	[136]
	Fucosterol	E. stolonifera and U. pinnatifida	10–100 μM (IC50 value of 64.12 ± 1.0 μM)	In vitro enzyme assay; In silico analysis	↓β-secretase activity; Binding energy (−10.1 kcal/mol)	-	Noncompetitive inhibition	[134]
	α-Bisabolol	Padina gymnospora	5 μg/mL	Thioflavin T (ThT), Confocal laser scanning microscopy (CLSM) analysis, Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopic analysis and molecular dynamics simulation	Prevents oligomers formation as well as disaggregates the matured fibrils	-	-	[137]
	Glycoprotein	U. pinnatifida	IC50 values of 73.35 ± 2.54 μg/mL	In vitro enzymatic assay	↓BACE1 activity	-	-	[75]
Cholesterol homeostasis and Aβ clearance activity	Fucosterol	-	100 and 200 μM (HEK293 cell cultures); 100 or 200 μM (macrophages and HepG2, H4IIE, and Caco2 cells)	HEK293 cell cultures (Reporter system); THP-1-derived macrophages; Caco-2 cells HepG2 cells	Reverses cholesterol transport. No accumulation of triglyceride in HepG2	n.d.	Dual-LXR agonist (LXR-α and LXR-β) ↑ABCA1, ABCG1, and ApoE; ↑Intestinal NPC1L1 and ABCA1; ↑Insig-2a, that delays nuclear translocation of SREBP-1c	[138]
	Saringosterol	Sargassum fusiforme	30 μM	Luciferase reporter assay system; HEK293T, THP-1 monocytes, HepG2, RAW264.7, THP-1 macrophages and Caco-2 cells	n.d.	n.d.	Selective LXRβ agonist; ↑ABCA1, ABCG1, and SREBP-1c	[139]
	Alginate-derived oligosaccharide	Marine brown algae		BV2 microglial cells	Microglial phagocytosis of Aβ	Toll-like receptor signaling	↑TLR4	[97].
Monoamine oxidase inhibition and affinity to dopaminergic receptors	Phlorofucofuroeckol-A and dieckol (phlorotannin)	-		In vitro enzyme assay and functional assay for GPCR screening; Docking analysis	↓hMAO activity; D3R and D4R stimulation	-	-	[140].
Antiaging	Sulfated oligosaccharides	U. lactuca and E. prolifera; green algae	150 mg/kg/day	Aging model (male senescence-accelerated prone (SAMP8) and male senescence resistant (SAMR1) mice)	Antioxidant and anti-inflammation	n.d.	↑GSH, SOD, CAT, telomerase levels, ↑Total antioxidant capacity, ↓MDA and AGEPs ↓IFN-γ, TNF-α, and IL-6 ↑BDNF and ChAT; ↑Sirt1, ↑p53 and FOXO1	[96]
	Fucosterol	Hizikia fusiformis	50 µg/mL	Culture model of C. elegans	Extends lifespan	↑Antioxidant mechanism	n.d.	[141]

n.d.: not defined; -: information not available.