Table 1.

Health-promoting effects of different species of the red alga genus, Chondrus.

Species	Extract Type	Target Models	Biological Activities	Ref.
Antimicrobial activity
C. crispus	Crude ethanol (95%) Dried and fresh extracts	Marine bacterial species: Pseudoalteromonas elyakovii, Polaribacter irgensii, Vibrio aestuarianus, Shewanella putrefaciens, and Halomonas marina Microalgae species: Chlorarachnion reptans, Chlorarachnion globosum, Exanthemachrysis gayraliae, Cylindrotheca cloisterium, Navicula jeffreyi	Potential antifoul activity Dried extracts had lower MIC than fresh extract. MIC (μg/mL) dried; fresh: P. elyakovii (10; 25), P. irgensii (10; 25), V. aestuarianus, (25; 50), S. putrefaciens, (25; 25), and H. marina (10; >50); C. reptans (10; 25), C. globosum (25; 10), E. gayraliae (10; 10), C. cloisterium (1; 10), and N. jeffreyi (25; 25).	[67]
C. crispus	Crude ethanolic extract of dried algae	Cobetia marina (50–200 ppm), Marinobacter hydrocarbonoclasticus (100–200 ppm)	Anti-biofilming effect	[68]
C.crispus	Methanol, ethanol and acetone (60%)	L. monocytogenes, P. aeruginosa, Salmonella abony, and E. faecalis	(%inhibition) (methanol; ethanol; acetone): L. monocytogenes (−3.88; 50.27; 56.13), S. abonya (−10.70; 0.80; 4.70), E. faecalis (−66.08; 100.00 ± 0.38; −89.74), P. aeruginosa (−31.72; 61.51; 81.74)	[69]
C. crispus	Ethyl acetate	S. enteridis, E. coli, P. aeruginosa, L. innocua, B. cereus, S. aureus, L. brevis. E. faecalis, Candida sp.from both wild and IMTA regimes	Ethyl acetate: inhibitory activity in both regimes; best in IMTA	[70]
	Diethyl ether		Diethylether extract: (1) IMTA regime: no effect against S. aureus (CI and FI), L. brevis and E. faecalis (2) wild regime: no effect against S. enteritidis
	Methanol:Water (1:1)		Methanol:Water extract: IMTA: no effect against Candida sp. Wild: no effect against S. enteritidis and S. aureus (CI)
C. crispus	Acidified ethanol	Bacterial species: Bacillus cereus, Micrococcus flavus, and Staphylococcus aureus, Proteus mirabilis, Salmonella Typhimurium Yeast species: Candida albicans C. tropicalis, and C. krusei	Anti-bacterial (mg/mL) (MIC, MBC): B. cereus (0.045, 0.06), M. flavus (0.09, 0.12), S. aureus (0.06, 0.1), P. mirabilis (0.045, 0.06), and S. Typhimurium (0.06, 0.12). Anti-fungal (mg/mL) (MIC, MFC): C. albicans (0.045, 0.06), C. tropicalis (0.045, 0.06), and C. krusei (0.06, 0.12).	[71]
Anti-stress and immunomodulation activity
C. crispus	Methanol extract (CCME)	Juglone (300 or 500 μmol)-induced Caenorhabditis elegans + CCME (1 mg/mL)	Anti-stress activity ↓ROS, stress response genes: ↑sod3, ↑hsp16.2, ↑skn1, ↑transcription factor daf16	[75]
C. crispus	Aqueous CCWE and K-CGN	Caenorhabditis elegans + infection with Pseudomonas aeruginosa PA14 CCWE (0, 250, 500, or 750 μg/mL) or K-CGN (200 μg/mL)	↑Survival rates CCWE = 500 μg/mL (optimum dose) and K-CGN Immune gene expression: ↑hsf-1, ↑irg-1, ↑irg-2, ↑F56D6.2, ↑F49F1.6, ↑K05D8.5, ↑C29F3.7, ↑ZK6.7, ↑abf-1 ↑F28D1.3, ↑F38A1.5, ↑lys-1, and ↑spp-1. Repressed QS (lasI/R and rhlI/R) systems. Virulene factor genes: ↓sbe, ↓hcnC, ↓aroE, ↓rpoN, and ↓sodB. Inhibited biofilm formation	[79]
Nitric oxide inhibition
C. crispus	Methanol extract of cultivated alga	RAW264.7 cells + LPS (1 µg/mL), extract (25, 50, and 100 µg/mL), 24 h	Dose-dependent NO inhibition	[64]
Neuroprotection
C. crispus	Methanol extract; organic fraction	C. elegans CL4176 + β amyloid toxicity organic fraction (0.1–1.0 mg/mL)	↓amyloid species deposition ↑antioxidant activity Stress response genes: ↑sod3, ↑hsp16.2, and ↑skn1	[82]
Improvement of gut health
C. crispus	Cultivated alga and FOS	Male Sprague Dawley rats (1) Basal diet (control) (2) the basal diet + 2.5% or 0.5% (dry w/w) of cultivated seaweed (3) basal diet + 2.5% or 0.5% of FOS (dry w/w)	No change in body and organs weights Cultivated alga extract (0.5%): ↑IgA, ↑IgG Alga extract (2.5%): Modulated gut microbiota ↑Bifidobacterium, ↑Legionella, ↑Sutterella, ↑Blautia, ↑Holdemania, ↑Shewanella, ↑Agarivorans and ↓Streptococcus ↑SCFAs	[85]
Antiproliferative activity
C. crispus	Methanolic extract Wild (high-UV and low-UV) and cultivated	HeLa cells and U-937 cells: 0.125, 0.5, 1,2, and 4 mg/mL, 24 h	Showed antiproliferative effect on HeLa cells: (upto 1 mg/mL): wild low-UV > wild high-UV > cultivated. (at 2 and 4 mg/mL) cultivated > wild low-UV > wild high-UV. U-937 cells: (upto 1 mg/mL): wild high-UV > wild low-UV > cultivated. Cutlivated extract in HeLa cells: ↑caspase-3,↑caspase-7; cell cycle arrest at Sub G1 (apoptotic) Antioxidant: reducing ability: cultivated > wild low-UV > wild high-UV ORAC: cultivated > wild low-UV > wild high-UV	[61]
C. crispus	Dried algal powder, 80% methanol	HepG2 cells, MCF7 cells, Caco-2 cells, and A549 cells, (0.01, 0.1, 1.0, 10, and 100 µg/mL), 24 h control (Sorafenib)	% inhibition (IC50 µg/mL): HepG2, control (1.32, 2.23); MCF7 cells, control (179, 4.0); Caco-2 cells, control (8.24, 2.88); A549 cells, control (7.90, 2.55)	[50]
C. crispus	Carrageenen fraction	A-2780, A-549, HT-29, and Hela-229 (0.1 mg/mL)	IC50 (mg/mL) = A-2780 (0.0080); A-549 (0.0099); HT-29 (0.0211); Hela-229 (0.0492)	[49]
Antioxidant activity
C. crispus	Dried algal powder 80% methanol	DPPH and ABTS assay: at 50, 100, 150, and 200 μg/mL TAC: at 100, 200, 300, and 400 μg/mL	DPPH (% inhibition): 50 μg/mL (25.0), 100 μg/mL (37.8), 150 μg/mL (47.3), and 200 μg/mL (84.2), BHT (μg) 91.5 ABTS (% inhibition): 50 μg/mL (82.0), 100 μg/mL (98.0), 150 μg/mL (108.9), and 200 μg/mL (120.3), Trolox (μg) (100.2). TAC: 100 μg/mL (88.48), 200 μg/mL (94.77), 300 μg/mL (136.88), and 400 μg/mL (235.81), vitamin C (μg) 243.46	[50]
C. crispus	Extract with UAE treatments	DPPH and ABTS @ 4 treatments (A) Probe 20 min; (B) Probe 40 min; (C) Bath 20 min; (D) Bath 40 min. Superoxide radical @ 2 treatments anion (C) and (D), 0.5, 1, and 2 mg/mL)	EC50 (mg/mL) DPPH: (A) ND, (B) 6.3, (C) ND, (D) 7.1 EC50 (mg/mL) ABTS: (A) 3.1, (B) 2.4, (C) 4.6, (D) 2.5 % inhibition (2 mg/mL): (C) 21.1 (D) 27.3	[65]
C. crispus	UAE extracted soluble extract	ABTS (1 mL) + 10 mL (soluble extract) or Trolox	Trolox equivalent antioxidant capacity (TEAC) = 182.4 mg/g	[49]
Antiviral activity
C. crispus	Enzymatic hydrolysates (P1, C1, C2, and C3)	African green monkey kidney cell line and HSV-1 (wild-type strain 17), hydrolysates (1–200 μg/mL (50 μL))	EC50 (μg/mL): 77.6 –126.8 μg/mL P1 (neutrase) = 77.6; C1 (cellulase) = 103.3; C2 (β-glucanase) = 126.8; C3 (ultaflo) = 109.3	[44]
Anticoagulation activity
C. crispus	Crude aqueous extract	0.125, 1.25, 12.5, and 125 μg/mL	Residual Xa activity * = C. crispus: 253; Heparin: 0.20; Lovenox®: 0.15; Residual IIa activity * = C. crispus: 194; Heparin: 0.25; Lovenox®: 1.8; APTT ** = C. crispus: 21; Heparin: 0.7; Lovenox®: 4.5; PT ** = C. crispus: >415; Heparin: 16; Lovenox®: 495; TT ** = C. crispus: <125; Heparin: 0.45; Lovenox®: 1.82	[45]
Antivenom activity
C. crispus	Lambda-carrageenan	In vitro assays Hemolytic/proteolytic activity: human erythrocytes and egg yolk emulsion (substrate) B. jararaca or B. jararacussu venom (20 μg/mL) + polysaccharide (200 μg/mL), 30 min at 25 °C Coagulation: venoms (10 μg/mL), + polysaccharide (200 μg/mL)	Inhibited hemolytic activity (60%) for B. jararaca Inhibited proteolytic activity: B. jararaca (65%) B. jararacussu (100%) Impaired plasma coagulation	[97]
		Balb/c mice Antihemorrhagic activity (a) Inhibtion protocol: incubation—polysaccharide (150 μg/mouse) or antivenon was mixed with 2 MHD of venom of B. jararacussu (50 μg/mouse) or B. jararaca (30 μg/mouse), 30 min, 25 °C. S.C. route (b) Treatment protocol: venoms (30 μg/mL, S.C.) + λ carrageenan 30 min later (S.C., samesite), or I.V. (c)venoms injection (S.C.), 30 min later (one injection) or 30 + 30 min (two injections) of polysaccharide (I.V.)	Inhibition protocol C. crispus polysaccharide inhibited venom’s hemorrhage: B. jararaca (40%) and B. jararacussu (100%). Treatment protocol C. crispus polysaccharide inhibited venom’s hemorrhage: B. jararaca (20%) and B. jararacussu (40%). C. crispus polysaccharide (one injection: two injections) inhibited venom’s hemorrhage: B. jararaca (20%:50%) and B. jararacussu (40%:60%).
		Antihemorrhagic activity of gel (a) Prevention protocol: Venoms dose (25 μg/mouse) (S.C.), + polysaccharide gel (100 μg) topically applied 15 or 30 min later, + antivenom single injection (I.V.) (b) Treatment protocol: gel containing λ polysaccharide (100 μg/mL) topical application + venoms (S.C., 25 μg/mouse) 15 or 30 min later.	Inhibition of hemorrhage after topical application of polysaccharide based gel, irrespective of protocol Hemorrhage of B. jararacussu was inhibited fully in a 30 min topical application before venom injection. Hemorrhage of B. jararacussu inhibited 30% in a 15 min topical application before venom injection
		Antidematogenic activity single, sub-plantar injection into the right paw (50 μL), after 1 h, the paw’s amputation. λ carrageenan (150 μg/mouse) or antivenom + venoms (25 μg/mouse), 30 min at 25 °C, injected (50 μL of the mixture) (S.C.) Protocol of treatment: venoms (S.C.), λ polysaccharide or venom 15 or 30 min later, (I.V.)	Inhibition (%) of edema (~30%) λ polysaccharide mixed with venom inhibited edema (45%) λ polysaccharide is more effective against B. jararacussu than B. jararaca
		Antilethal activity Protocol of incubation: venoms (130 μg/mouse) + λ polysaccharide (100 μg/mouse) or antivenom, 30 min at 25 °C (I.P. injection) Protocol of treatment: I.P. injection of venoms, 30 min later, λ polysaccharide or antivenon (I.V.).	Polysaccharide + venom protected the mice (both treatments)
		Antimyotoxic activity Protocol of incubation: B. jararacussu venom (50 μg/mouse) + polysaccharide (150 μg/mouse), saline or antivenon, 30 min at 25 °C, 100 μL injection. Protocol of treatment: B. jararacussu venom (I.M.), polysaccharide, antivenom, or polysaccharide + antivenom, 30 min later (I.V.)	Inhibited myotoxic activity. Slight protection was observed.
Antitumor and immunomodulation
C. ocellatus	EA polysaccharides: PC1, PC2, PC3, PC4, and PC5	ICR mice, S180 and H22 tumor cells (subcutaneous implatation), 0.2 mL of each extract (200 mg/kg/day) for 7 days	Inhibited tumor growth (%) PC1, PC2, PC3, PC4, and PC5 S180: (57.58,37.64, 44.35,50.52, and 66.15) H22: (57.03,61.90, 23.22,68.97, and56.90) ↑spleen weights, ↑NK cell activity, ↑lymphocyte proliferation	[98]
C. ocellatus	Polysaccharide PC5	ICR mice, S180 (subcutaneous implatation) (1) 5-FU:25 mg/kg (2) PFp1 PC5:100 mg/kg (3) PFp2 PC5:50 mg/kg (4) PF1 PC5+5-FU:100 + 25 mg/kg (5) PF2 PC5+5-FU 50 + 25 mg/kg	Inhibited tumor growth (%): 5-FU: (37.30), PFp1: PC5 (32.08), PFp2: PC5 (26.03), PF1: PC5+5-FU (63.87), PF2: PC5+5-FU (55.40) ↑TNFα ↑lymphocyte proliferation ↑spleen weights	[99]
C. ocellatus	Polysaccharide PC4	ICR mice, H22 (subcutaneous implatation) (1) 5-FU:25 mg/kg (2) HFp1 PC4:100 mg/kg (3) HFp2 PC4:50 mg/kg (4) HF1 PC4+5-FU:100 + 25 mg/kg (5) HF2 PC4+5-FU 50 + 25 mg/kg	Inhibited tumor growth (%) 5-FU: (30.76), HFp1 PC4: (43.97), HFp2 PC4: (35.37), HF1 PC4+5-FU: (51.73), HF2 PC4 + 5-FU (47.01) ↑lymphocyte proliferation ↑TNFα ↑spleen weights	[100]
Anti-inflammatory activity
C. ocellatus Holmes	Ethanol extract (COHEE)	LPS +RAW 264.7 cells, (0.1, 1, 10, 50, and 100 μg/mL), 22 h	No cytotoxic effects ↓NO, ↓IL-6, ↓TNF-α, ↓IL-1β, ↓iNOS, ↓COX-2, ↓NF-κB p65, ↓p-MAPK	[101]
		Croton oil-induced mouse ear edema model, COHEE (10, 50, and 250 mg/kg BW), 200 μL, croton oil (2.5%, 20 μL/ear), 1 h before treatment	↓Mouse ear edema at a higher dose ↓Mast cell number
Antidiabetic activity
C. ocellatus	Ethanol extract (61%)	In vitro assay	Anti-radical activity: DPPH = (13.11–25.77%), ABTS = (43.48–53.50%) H2O2 inhibition (IC50) = 18.4–85.6 U/mL α-glycosidase inhibition: IC50 = 16.92 mg/mL α-glucosidase inhibition: 375.3 mg/mL	[102]
Cytoprotective and antimicrobial activity
Mazzaella canaliculata	Methanol extract	In vitro assays	DPPH radical scavenging: IC50 = 0.25 mg/mL Antimicrobial activity: Salmonella Typhimurium, Klebsiella pneumoniae, Listeria monocytogenes, Actinomyces sp., Enterococcus faecalis, Enterobacter sp., and Micrococcus luteus	[103]
		Wistar female rats (1) Non-treated rats (positive control). (2) maneb (MB I.P.)/kg (300 mg). (3) 300 mg/kg of MB (I.P.) + algal extract (150 mg/kg, oral) (4) algal extract (150 mg/kg), positive control group, 7 days	MB-treated group: ↓body weight, ↓RBC, ↓WBC, ↓viability, ↑DNA damage, ↑platelet rates Co-treated: ↑body weight, ↑RBC, ↑WBC, ↑viability; ↓DNA damage, lowered platelet rates compared to the MB-treated group. Improved mineral levels in blood, bone, and urine In co-treated erythrocyte and bone: ↓MDA, ↓AOPP, ↑SOD, ↑GSH, and ↑GPx
Mazzaella canaliculata	Polysaccharide (CCP)	2, 4, 6, 8, 10, and 12 mg/mL	DPPH (2 mg/mL) has strong antiradical activity comparable to gallic acid. Protective effect against β-Carotene bleaching inhibition assay (10 mg/mL = 39.90%) Ferrous ion chelation: 10 mg/mL = 96.37% Ferric-reducing activity: 10 mg/mL = 2.16 Protection against hydroxyl radical-induced DNA damage	[104]
		Wistar female rats Group 1: control group (saline) Group 2: MB (300 mg/kg, I.P.) Group 3: MB (300 mg/kg, I.P.) + CCP (100 mg/kg), Group 4: MB (300 mg/kg, I.P.) + CCP (200 mg/kg), Group 5: CCP (100 mg/kg, I.P.) (positive control) Group 6: CCP (200 mg/kg, I.P.) (positive control)	Dose-dependent significant improvement in MB’s oxidative and histological injuries. In plasma: ↓urea, ↓creatinine, ↓albumin Co-treatment: ↓MDA, ↓AOPP, ↑SOD, ↑GSH, and ↑GPx Co-treatment: ↑RBCs, ↑WBCs, ↑iron, ↑MCV, ↑MCH and ↑MCHC ↓apoptosis
Anti-atopic activity
Mazzaella canaliculata	Ethanolic extract (CCEE)	BALB/c mouse 1% (w/v) DNCB, 3 times a day; after 1 week, apply 0.3% (w/v) DNCB to the same area once a day (200 μL) DNCB + CCEE	↓IFNγ, ↓IL-4 ↓clinical severity score	[105]
Anti-inflammatory activity
C. armatus	LMW and HMW carrageenan	Acetic acid-induced colitis in male Swiss mice + oral pretreatment (carrageenan in H2O) (5, 10, 50 mg/kg)	HMW: ↓ colon damage, ↓MPO. Effective dose: 5 mg/kg LMW: no protective effect.	[106]
Antitumor and immunomodulation activity
C. armatus	Native κ- and λ-carrageenans LMW κ- and λ-carrageenans degradation products	FLO1, KYSE30, and human dermal fibroblast cell lines Treatments: 50, 100, and 400 μg/mL, 24 or 48 hr PBMC + test polysaccharides (1, 10, or 100 μg/mL) or LPS (0.1 μg/mL), 24 h	↓ FLO1 and KYSE30 viability. All polysaccharides showed anti-metabolic activity. In FLO1: LMW κ- and λ-carrageenan were more effective (at 400 μg/mL): LMW κ (%): 48; HMW κ (%): 97.7. LMW λ (%) 61.9; HMW λ (%) 79.1. In KYSE30, naïve κ- and λ-carrageenans were more effective: κ-carrageenans (%) 47.5;. λ-carrageenans (%) 55.1. All carrageenans: induce monocytes to produce cytokines: IL1β, IL6, IL18, and TNFα. LMW λ-carrageenan only: IL10	[107]
C. armatus	κ- and λ-carrageenans Native or HMW. LMWDPs	In vitro: murine peritoneal macrophages Control, LPS, HMW-κ, LMWDPs-k, HMW-λ, LMWDPs-λ (1, 10, and 100 μg/mL) or LPS (0.1 μg/mL)	↓phagocytic activity by molecular weight and chemical structure-dependent manner. Anti-phagocytic efficacy = κ-carrageenan > λ-carrageenan At 100 μg/mL: LMWDPs-κ, HMW- λ, no effect on phagocytosis. HMW-κ reduced by 34%	[108]
		In vivo: male C57BL/6 mice Control, LPS, stress, HMW-κ and λ, LMWDPs-κ and λ, 100 μg/kg/day, 7 days	No significant change in body weight or internal organs. Total leucocyte counts = not affected except for κ-carrageenan. Cell motility: LMWDPs (κ): no effect; LMWDPs (λ): 24% reduction. HMW (λ): ↑peritoneal macrophages (40%).
C. armatus	κ- and λ-carrageenan	KYSE-30, FLO-1, HCT-116, RKO, and RPE-1 cell lines	Cytotoxicity (IC50 values) of κ- and λ-carrageenan: KYSE-30: 394, 392; FLO-1: 405, 184; HCT-116: 347, 206; RKO: 350.6, 248.3; RPE-1: 728, 615. Delayed cell cycle at different stages. λ-carrageenan in RKO: ↓CDK2, ↓E2F2, ↓cyclin E. Induction of apoptosis	[109]

MIC: minimum inhibitory concentration; IMTA: integrated multitrophic aquaculture system; CI: clinical isolate; FI: food isolate; MBC: minimum bactericidal concentration; MFC: minimum fungicidal concentration; CCWE: Chondrus crispus water extract; ROS: reactive oxygen species; sod3: superoxide dismutase 3; hsp16.2: heat shock protein 16.2; skn1: skin head 1; K-CGN: kappa-water-soluble polysaccharide carrageenan; hsf-1: heat shock factor1; irg-1/2: infection response gene 1/2; F56D6.2: C-type lectin; F49F1.6: ShK domain-like, secreted surface protein; K08D8.5/C29F3.7: CUB-like domain; ZK6.7: lypase; abf-1: antibacterial protein; F28D1.3: thaumatinlike protein; F38A1.5: lectin family protein; lys-1: lysozyme-like protein; spp-1: saponin-like protein; QS: quroum sensing; LPS: lipopolysaccharide; NO: nitric oxide; FOS: fructooligosaccharides; IgA: immunoglobulin A; IgG: immunoglobulin G; SCFAs: short -chain fatty acids; UV: ultra violet; ORAC: oxygen radical absorbance capacity; IC₅₀: half maximal inhibitory concentration; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid; TAC: total antioxidant capacity; BHT: butylated hydroxy toluene; UAE: ultrasound-assisted extraction; ND: not defined; P: proteases; C1/2/3: carbohydrases; HSV-1: Herpes simplex virus-1; EC₅₀: half maximal effective concentration; APTT: activated partial thromboplastin time; PT: prothrombin time; TT: thrombin time; SC: subcutaneous; IP: intraperitoneal; IV: intravenous; IM: intramuscular; λ: lambda; ICR: institute of cancer research; NK: natural killer; 5-FU: 5-Fluorouracil; TNF-α: tumor necrosis factor-alpha; IL: interleukin; IL-1β: interleukin-1beta; iNOS: inducible nitric oxide synthase; COX-2: cyclooxygenase-2; NF-κB p65: nuclear factor-kappa B p65; p-MAPK: phosphorylated mitogen-activated protein kinase; BW: body weight; H₂O₂: hydrogen peroxide; MB: manganousethylenebis (dithiocarbamate); RBCs: red blood cells; WBCs: white blood cells; DNA: deoxyribonucleic acid; MDA: malondialdehyde; AOPP: advanced oxidation protein products; SOD: superoxide dismutase; GSH: glutathione; GPx: glutathione peroxidase; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; DNCB: 2,4-Dinitrochlorobenzene; IFNγ: interferone gamma; PTX: paclitaxel; PBMCs: peripheral blood mononuclear cells; κ: kappa; LMW: low molecular weight; HMW: high molecular weight; MPO: myeloperoxidase; LMWDPs: low-molecular-weight degradation products; CDK2: cyclin-dependent kinase 2; E2F2: E2F transcription factor 2; ↑: increased; ↓: decreased. * Inhibiting (IC₅₀) the coagulation factor residual activity. ** Enabling the doubling of the coagulation time of the negative control (NaCl 0.9%).