Table 3.

Anti-inflammatory potential of COS.

Sample	Model	Reported activity	References
COS	In vivo paw edema rat model	The anti-inflammatory activity is related to COS dose and their MWt.	[16]
COS	BV-2 microglia	Inhibitory effects on generation of interleukin IL-1b, IL-6, and TNF-α; blocking degradation of IκB-a inhibitor; transfer of NF-κB and MAPK.	[21]
COS	Human umbilical vein endothelial cells	Inhibition of LPS-induced cell apoptosis; increase of caspase-3 and regulation of the conductance calcium-stimulated potassium channel.	[42]
COS	L9 microglial cells (in vitro)	Suppression of nitric oxide generation; inhibition of p38 MAPK phosphorylation and decreased AP-1 and NF-κB activation.	[35]
COS	Autoimmune anterior uveitis model (in vitro)	Clinical score reduction; reducing the inflammatory markers such as MCP-1, iNOS, RANTES, and TNF-α.	[44]
COS	In vivo acute renal failure model	Antioxidative activity enhanced kidney tasks.	[51]
LM-COS	RBL-2H3 cells (in vitro) and ovalbumin-sensitized/challenged mouse asthma model (in vivo)	Decrease the generation and activation of inflammatory cytokines.	[53]
Soluble (S) and insoluble (B) COS	Spleen CD11c+ dendritic cells (SDCs)	B-COS induce SDC maturity, TNF secretion, and promotion of CD4+T proliferation; COS bioactivity depends on MWt or degree of polymerization.	[54]
N-acetyl-D-glucosamine oligosaccharides	In vitro and ex vivo skin epithelial cells and tissues; ex vivo GIT epithelial membranes	Activation of skin cells' differentiation; increasing the mucin secretion from GIT cells.	[55]
COS-supplemented diet	LPS-challenged piglets	Decrease the inflammation of the intestine, through CaSR activation and suppression of NF-κB pathway.	[74]
COS	RAW 264.7 cells (LPS-activated murine macrophage)	Induction of HO-1 activation; reduction of iNOS and COX-2; activation of ERK1/2, JNK, and p38 MAPK signaling pathways.	[56]
S-COS (crab shells)	RAW 264.7 cells (murine macrophage)	Suppression of proinflammatory markers such as iNOS and NO.	[57]
COS (MWt∼5000 Da, DD ∼90%)	Rabbit and human synoviocytes	Induction of AMPK activation; increase in the ADP/ATP ratio; suppression of TNF-α-mediated COX-2 and iNOS activation through AMPK pathway.	[58]
Chitobiose, chitotriose, chitotetraose, chitopentaose, and chitohexaose	Cell line, 293T	Activation of NF-κB-dependent luciferase genes and downstream of transcription of NF-κB genes.	[59]
COS	Endothelial cells (cultured) and mice model	Suppression of LPS-induced NF-κB-dependent inflammatory gene expression; decrease in OGT-dependent O-GlcNAcylation of NF-κB; attenuation of LPS-stimulated inflammation.	[60]
COS nanoparticles	Mouse fibroblasts (3T6), HeLa cells, and melanoma cells (B16)	Induction of the proliferation of fibroblasts; modulation of Th cytokines; stimulation of spleen's lymphocyte proliferation.	[61]
COS	Human umbilical vein endothelial cells	Inhibition of TNF-α-stimulated activation of ICAM-1 and VCAM-1 at the translation and transcription stages; block the TNF-α-stimulated expression of NF-κB; block the decomposition of IκB-a and the activation of ERK1/2 and p38 MAPK; reduce the adhesion of U937 monocyte to HUVECs; suppression of ICAM-1 and VCAM-1 generation in activated HUVECs.	[62]
COS	Septic mice	Reduction of blood IL-1β and TNF-α; attenuation of p38-activated protein kinase and c-Jun NH2-terminal kinase.	[63]
COS	Epithelial GE11 cells	Epidermal growth factor (EGF)-induced epithelial GE11 cells growth inhibition; block EGFR phosphorylation and MAPK activation.	[65]
COS	Human breast epithelial cells (MCF-10A)	Inhibition of cell migration induction; suppression of GnT-V protein expression.	[66]
Galacto-mannan-oligosaccharides	Early weaned piglets	Enhance IL-1β gene activation in mucosa of jejuna and lymph nodes; improve the blood levels of IgM, IgG, IgA, IL-6, IL-2, and IL-1β.	[67]
COS	LPS-induced (RAW 264.7 cells)	Inhibition of LPS binding to TLR4/MD-2 receptor complex; attenuation of the stimulation of MAPK; decrease in NF-kB nuclear transmission; reduction in proinflammatory generation (IL-1, NO).	[68]
COS	ICR male mice; T84 cells (human epithelial cells of colon)	Suppression of stimulation of NF-κB and contents of IL-6 and TNF-α in colon cells; failure of the epithelial barrier to function.	[69]
COS	RAW 264.7 macrophages. ICR mice	Enhance the phagocytosis by macrophages; increase the generation of nitric oxide and TNF-α by macrophages; increase the TLR4 and inducible iNOS mRNA levels.	[70]
COS	Sprague Dawley neonatal rats	Inhibit cell apoptosis; improve mitochondrial membrane potential and IL-1β-induced nuclear chromatin damage in chondrocytes; activate the p38 MAPK signaling pathway.	[71]
COS	Obese model (in vivo)	Reduction in the weight increase through inhibition of inflammation.	[75]
COS	Sepsis model (in vivo)	Decreased organ malfunction and enhanced the rate of surviving.	[76]
COS	BV-2 microglial cells (in vitro)	Decreased PGE2 and NO generation through suppressing the activation of COX-2 and iNOS; reduced the IL-1β, IL-6, and TNF-α contents; inhibited p38 MAPK and JNK activation.	[77]
COS	Human umbilical vein endothelial cells	Suppression of LPS-mediated IL-8 activation through blocking the p38 and Akt protein kinases.	[78]
COS	S. aureus isolated from mastitic cows	Antibacterial activity against S. aureus. Immunostimulatory effect; enhancement of nonspecific immunity cells through raising monocytes.	[79]
COS	Hybrid tilapia (Oreochromis niloticus × Oreochromis aureus)	Decrease the mRNAs encoding and TNF content; increase of transforming growth factor-b levels; reduction of A. hydrophila infection.	[80]
Deacetylated COS	RAW macrophages	Increase of the cell viability; moderate anti-inflammatory activity.	[73]
COS	IPEC-J2 (porcine intestinal epithelial cells)	Attenuation in activation of mRNA of MCP-1 and IL-8 stimulated through TNF-α; decrease of mRNA expression of claudin-1.	[81]