A review of the immune activity of chitooligosaccharides

WANG, Yuanyuan; ZHAO, Kui; LI, Li; SONG, Xuena; HE, Yao; DING, Ning; LI, Lijie; WANG, Shanglong; LIU, Zimin

doi:10.1590/fst.97822

Yuanyuan WANG

writing of the main manuscript

Qingdao Chenland Health Industry Group Co., Qingdao city, Shandong Province, China

https://orcid.org/0000-0001-5346-4931

Kui ZHAO

preparation of figures

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China

Li LI ^**Corresponding author: lli@chenland.com

conception design

Chenland Nutritionals, Inc, Irvine, CA, United States

Xuena SONG

collection of references

Qingdao Chenland Health Industry Group Co., Qingdao city, Shandong Province, China

Yao HE

collection of references

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China

Ning DING

collection of references

Malvern College Qingdao, Qingdao, China

Lijie LI

conception design

Qingdao Engineering Vocational College, Qingdao, Shandong Province, China

Shanglong WANG

conception design

Qingdao Chenland Health Industry Group Co., Qingdao city, Shandong Province, China

Zimin LIU

conception design

approval of the manuscript

Chenland Nutritionals, Inc, Irvine, CA, United States

*Corresponding author: lli@chenland.com

Conflict of interest

The authors declare that there are no conflicts of interest.

Author contributions

L. L., L. L. and S. W. designed the conception. Y. W. wrote the main manuscript text, K. Z. prepared figures 1 -3. X. S., Y. H., and N. D. collected references. Z. L. designed the conception and approved the manuscript. All authors reviewed the manuscript.

Methods	Advantage	Disadvantage
Chemical method	Easy operation	1. difficulty products separation
Chemical method	Easy operation	2. serious environmental pollution
Physical method	Easy purification	Low yield
Non-specific enzymatic hydrolysis method	1. Friendly environment	Lower degradability and productivity
	2. Higher efficiency
	3. Controllable operation and monitoring
Chitosanase hydrolysis method	Directly produce the desired degradation products without degrading other groups of the substrate	1. Limited sources of enzymes
Chitosanase hydrolysis method		2. Limited volume-produce

MW/DP	Content	Effect strain
2000-3000Da	0.1%	Actinomycetes
—	0.1%	Streptococcus mutans
<3000Da	0.25%	Staphylococcus aureus
<1500Da	0.5%	Escherichia coli
<1500Da	0.5%	Lactobacillus rhamnosus
DP=2~6	0.3%	Bacillus cereus
<1000Da	5 mg/mL (0.5%)	Listeria monocytogenes
DP=4~5	100 mg/mL (0.01%)	Bacillus subtilis
		Staphylococcus aureus
		Escherichia coli
DP=2~8	0.1%	Lactobacillus brevis
DP=2~8	0.1%	Lactobacillus casei
<1000 Da	100mg/kg (0.01%)	Bifidobacterium

Source: Ying et al. (2002)Ying, G. S., Lin, R., & Yuan, L. B. (2002). Study on the microecological effects of chitooligosaccharides. Chinese Journal of Microecology.; Koppová et al. (2012)Koppová, I., Bureš, M., & Simůnek, J. (2012). Intestinal bacterial population of healthy rats during the administration of chitosan and chitooligosaccharides. Folia Microbiologica, 57(4), 295-299. http://dx.doi.org/10.1007/s12223-012-0129-2. PMid:22528304.
http://dx.doi.org/10.1007/s12223-012-012... ; Zhang (2019)Zhang, B. (2019). Dietary chitosan oligosaccharides modulate the growth, intestine digestive enzymes, body composition and nonspecific immunity of loach Paramisgurnus dabryanus. Fish & Shellfish Immunology, 88, 359-363. http://dx.doi.org/10.1016/j.fsi.2019.03.006. PMid:30851451.
http://dx.doi.org/10.1016/j.fsi.2019.03.... ; Li et al. (2019)Li, J., Cheng, Y., Chen, Y., Qu, H., Zhao, Y., Wen, C., & Zhou, Y. (2019). Dietary chitooligosaccharide inclusion as an alternative to antibiotics improves intestinal morphology, barrier function, antioxidant capacity, and immunity of broilers at early age. Animals, 9(8), 493. http://dx.doi.org/10.3390/ani9080493. PMid:31357589.
http://dx.doi.org/10.3390/ani9080493... ; Chae et al. (2005)Chae, S. Y., Jang, M. K., & Nah, J. W. (2005). Influence of molecular weight on oral absorption of water soluble chitosans. Journal of Controlled Release, 102(2), 383-394. http://dx.doi.org/10.1016/j.jconrel.2004.10.012. PMid:15653159.
http://dx.doi.org/10.1016/j.jconrel.2004... ; Sánchez et al. (2017)Sánchez, Á., Mengíbar, M., Rivera-Rodríguez, G., Moerchbacher, B., Acosta, N., & Heras, A. (2017). The effect of preparation processes on the physicochemical characteristics and antibacterial activity of chitooligosaccharides. Carbohydrate Polymers, 157, 251-257. http://dx.doi.org/10.1016/j.carbpol.2016.09.055. PMid:27987925.
http://dx.doi.org/10.1016/j.carbpol.2016... ; Wu et al. (2013)Wu, S. J., Pan, S. K., Wang, H. B., & Wu, J. H. (2013). Preparation of chitooligosaccharides from cicada slough and their antibacterial activity. International Journal of Biological Macromolecules, 62, 348-351. http://dx.doi.org/10.1016/j.ijbiomac.2013.09.042. PMid:24095661.
http://dx.doi.org/10.1016/j.ijbiomac.201... ; Wan et al. (2017)Wan, J., Jiang, F., Xu, Q., Chen, D., Yu, B., Huang, Z., Mao, X., Yu, J., & He, J. (2017). New insights into the role of chitosan oligosaccharide in enhancing growth performance, antioxidant capacity, immunity and intestinal development of weaned pigs. RSC Advances, 7(16), 9669-9679. http://dx.doi.org/10.1039/C7RA00142H.
http://dx.doi.org/10.1039/C7RA00142H... .

MW/DP	Content	Model	Item
1000 Da	0.04 g/kg	Immunodeficient mice	NK cell activity
			Immune organ index
			Phagocytic index
DP=3~7	0.6 g/kg	Mouse	Serum IgG content
DP=4~11	0.25, 0.5, 1 g/kg	Cy-treated mice	IL-2
			IL-12
			IFN-γ
			IL-10
			Immune organ indices
			DTH reaction, Footpad thickness
			Phagocytic activity
			ACP activities
			LDH activities
1000 Da, 3000 Da and 8000 Da	0.8 g/kg	Tilapia	Phagocytic activity of leucocytes, Phagocytic index of leucocytes
_	0.1, 0.2, 0.3 g/kg	mice genital tract infected by Chlamydia trachomatis	IgG, IL-11,spleen and thymus indexes
DP=3~5	0.1, 1, 10, and 100 µg/mL,	RAW 264.7	Macrophage phagocytosis capacity assay
	0.1, 1, 10, or 100 µg/mL	Mouse splenic lymphocyte	Splenic lymphocyte proliferation
	0.1, 1, 10, or 100 µg/mL	Splenic natural killer cell	NK cells activity
	33, 100 and 333 mg/kg	Rats	Thickness of the paw, Spleen and thymus indices, Mononuclear phagocytic system (MPS) function

MW	Content	Model	Item
1000~3000Da	500 µg/mL	HT1080 cell	MMP-9
—	1, 2, 3, 4 and 5 mg/mL	SW480 cell	Inhibition rate
DP=2~6	100 pg/mL	ECs cell	IL-8
1000~3000Da	0.1, 0.5, 1, 3, 5 mg/mL	MDA-MB-231 cell	Invasive inhibition rate
1000~3000Da	0.1, 0.5, 1, 3, 5 mg/mL	HT-29 cell	NO inhibition rate
DP=3~8	500 mg/kg	Llc mice	Rate of lung metastases

Item	Results
Ames test	Non-mutagenic
micronucleus assays	1 mg/mL did not induce any genetic alterations in human lymphocytes
comet assays
micronucleus test and the chromosomal aberration test	5 g/kg/day for 180 days had no effects on the frequency of micronuclei and chromosomal aberrations in bone marrow cells in mice
Cytotoxicity	IC50 of 5 mg/mL
Acute toxicity	The median lethal dose (LD50) of COS is > 10 g/kg
Subacute toxicity studies	The no observed adverse effect level (NOAEL) of COS is > 3 g/kg/day for rats of either sex
	The NOAEL of COS is >500 mg/kg/day in mice
	The NOAEL of COS in the subchronic toxicity study is equal to 0.2% (w/w) or 124 mg/kg/day in male rats and 142 mg/kg/day in female rats

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[1] *Corresponding author: lli@chenland.com

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A review of the immune activity of chitooligosaccharides

Abstract