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Guan, Z.;  Feng, Q. Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics. Encyclopedia. Available online: https://encyclopedia.pub/entry/24336 (accessed on 15 December 2025).
Guan Z,  Feng Q. Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics. Encyclopedia. Available at: https://encyclopedia.pub/entry/24336. Accessed December 15, 2025.
Guan, Zhiwei, Qiang Feng. "Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics" Encyclopedia, https://encyclopedia.pub/entry/24336 (accessed December 15, 2025).
Guan, Z., & Feng, Q. (2022, June 22). Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics. In Encyclopedia. https://encyclopedia.pub/entry/24336
Guan, Zhiwei and Qiang Feng. "Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics." Encyclopedia. Web. 22 June, 2022.
Chitosan and Chitooligosaccharide as Non-Plant-Derived Prebiotics
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This entry is adapted from the peer-reviewed paper 10.3390/ijms23126761

Chitin was first isolated from a mushroom by French chemist Henri Braconnot in 1811. It is the second-most abundant natural long-chain polymer, after only cellulose. Chitin is composed of N-acetyl-glucosamine monomers linked by a β-1,4-glycosidic bond, with the degree of polymerization (DP) ranging from about 1000 to 3000. This polymer widely exists in the exoskeleton of crabs, shrimps, and insects, as well as in the cell walls of fungi, where it forms a highly ordered crystal structure and plays a role in supporting and protecting cells. Chitin with a high molecular weight (MV) and a degree of acetylation (DA) over 90% is highly hydrophobic and hardly dissolves in water and most solvents.

chitosan chitooligosaccharide prebiotic

1. Production, Physicochemical Properties, and Applications of Chitosan and Chitosan and Chitooligosaccharide (COS)

Chitosan is the deacetylated product of chitin. The chitin existing in the exoskeletons of marine crustaceans (e.g., shrimp, crab, squid, and lobster), where it is closely combined with other components, such as protein, minerals, lipids, and pigments, is the traditional source for chitosan production. In order to extract pure chitosan from crustacean shell waste, severe chemical treatments are required, including removing impurities such as protein and calcium salt. Then, deacetylation is performed with concentrated aqueous alkali (e.g., 10–15 M NaOH or KOH) at a high temperature of 40 to 100 °C. However, chitosan obtained via the above treating methods suffers from such physicochemical defects as protein contamination and inconsistent levels of deacetylation and MW. Furthermore, environmental pollution, seasonal limitation of raw material supply, and high production cost are also inconvenient problems [1]. Recently, microwave irradiation combined with chemical and enzymatic methods has been used to prepare chitosan, which effectively shortens the time of chitin deacetylation [2]. Fungal mycelium is another abundant, steady, and economical source of chitin. Compared with the traditional crustacean resource, fungal mycelium has no allergenic marine crustacean protein and lower inorganic content, for which demineralization is not required when processing. Meanwhile, the extraction of chitosan from the fungi-derived chitin can be achieved via treatments using acids and alkali with very low concentrations, which has better environmental safety and is considered a feasible green method in laboratories [3]. Additionally, the preparations of chitosan by ionic liquid and via microbial fermentation or the proteolytic enzymes produced by bacterial communities are also promising and eco-friendly extraction processes [4]. When the degree of deacetylation (DD) reaches 50%, chitosan obtains water solubility and viscosity at acidic pH due to the protonation of amino groups in the polymer molecule [5]. Chitosan dissolves more easily as its DD increases. Commercial chitosan has a DD of up to 90% [6]. Based on the application requirements, chitosan can be processed into different conformations, including fiber, film, sponge, beads, gel, solution, and nanoparticles [7][8]. Compared with chitin, chitosan is not only less toxic and less allergenic but also has better adsorbability, permeability, and abilities of film-forming and moisturizing. These unique structural and physicochemical properties endow chitosan with wider application prospects in the fields of food, medicine, cosmetics, agriculture, and so on [9]. Due to the abilities of its hydroxyl and amino groups to adsorb or chelate such pollutants as dyes, metal ions, and organic compounds under different pH conditions, chitosan is usually utilized in wastewater treatment [10][11]. Chitosan is also recognized as a food additive. It can be used as an inhibitor of browning and as a clarifying agent in juices [12], as well as as a preservative and antioxidant in processed meat [13]. In plant protection, chitosan-based materials are prospective drugs against phytopathogenic fungi owing to their antifungal and biodegradability characteristics [14]. In the field of medicine, chitosan can be used as a lipid-lowering drug. First, soluble chitosan is dissolved in gastric acid and then reaches the small intestine, where it combines with cholic acid to form an insoluble complex. Next, this complex is excreted from the body through feces so as to reduce the absorption of cholic acid and lower the serum level of cholesterol [15]. Chitosan also can promote wound healing and be used as a carrier to assist the delivery and transport of macromolecular drugs, vaccines, and nucleic acids [16][17][18][19]. In recent years, chitosan, as a new biomaterial particularly in stomatology, has been applied in oral surgery, restorative dentistry, and improving periodontal disease due to its fine antimicrobial and drug-delivering properties [20]. For example, chitosan can be used in dental cements to reduce the formation of bacterial biofilm or be added to toothpastes as a demineralizer [20]. Additionally, it also shows good potential in inducing periodontal, bone, cartilage, vascular system, neural network, and skin tissue regeneration [21][22]. As the electrospun material for bioink, chitosan has been utilized to produce 3D-printed scaffolds applied in tissue engineering and drug delivery. In contrast to conventional 3D scaffolds such as gels and fibrous matrices, the chitosan-based material can recapitulate native tissues with high exactness due to its better mechanical stability, cellular adhesion, and biocompatibility [23]. Although superior to chitin, some physicochemical flaws of chitosan (e.g., low water solubility, high viscosity, slow gelation rate, and weak mechanical strength) limit its utilization. To compensate for this, the plentiful hydroxyl and amino groups on the molecule of chitosan can be modified to a certain extent via chemical methods, including acylation, carboxylation, alkylation, quaternization, and graft copolymerization, as well as physical and enzymatic methods [23][24][25][26][27][28]. These reasonable modifications of chitosan can improve such physicochemical and biological properties as solubility, thermal stability, rheology, antioxidant effect, biocompatibility, and antimicrobial effect in order to broaden its applications in various fields. In addition, as the MV of chitosan reduces, the number of hydrogen bonds in the polymer chain and between chains decreases, which makes the molecules loose and easier to dissolve [29]. Therefore, hydrolyzing the glycosidic bonds between glucosamine units in chitosan to lower the MV is a reasonable strategy for improving its solubility and application performance. Perhaps this is the reason why COS has attracted extensive attention of many researchers.
COS is the hydrolysis product of chitosan, which is usually defined as those polymers/oligomers with a degree of DD of more than 90%, a DP of fewer than 20, and an average Mw of less than 3.9 kDa [30]. Hydrolysis of chitosan can be carried out by chemical or enzymatic methods, among which chemical hydrolysis by acid or oxidizer is often applied in industrial production of COS [31]. In spite of the lower cost of production, chemical hydrolysis is frequently limited by the lack of an effective technique for the large-scale production of COSs with specific MVs. Additionally, the potential risks in environmental pollution and formation of toxic byproducts are also shortcomings, causing doubts and criticism [32]. As an eco-friendly technology, the enzymatic method applied in the hydrolysis of chitosan makes up for these shortcomings derived from chemical hydrolysis. This method can be manipulated under moderate conditions to produce safe and bioactive COSs. Many enzymes have been utilized in the hydrolysis of chitosan, of which chitinase and chitosanase have a high substrate specificity to chitosan. Several nonspecific enzymes such as protease, lipase, cellulase, hemicellulase, lysozyme, pectinase, and α-amylase can also be applied this process [33]. Meanwhile, the development and application of immobilized enzyme technology reduce the production cost and achieve the continuous production of COS [34].

2. Pharmacokinetic Characteristics of Chitosan and COS

Because of the lack of digestive enzymes (e.g., chitinase, chitosanase, cellulase, hemicellulase, and pectinase) which can hydrolyze β-1,4-glycosidic bonds in human digestive fluid, chitosan and COS can hardly be degraded in the small intestine. However, based on good biocompatibility, chitosan and COS can be absorbed by the gut and further metabolized. Understanding the pharmacokinetic characteristics of chitosan and COS is of great significance for safe and efficient medical applications. The absorption and metabolism of chitosan and COS have so far been analyzed and elucidated by fluorescein isothiocyanate (FITC) labeling technology. Chea et al. investigated the impact of molecular weight on the absorption of water-soluble chitosan by both in vitro and in vivo experiments with Caco-2 cells and male Sprague Dawley (SD) rats, respectively. The results revealed that soluble chitosan and COS can be absorbed via intestinal epithelial cells, and the absorption was significantly influenced by MW, with the absorption decreasing as the MW increased. Compared with the poorly absorbed chitosan with an MV of 230 kDa, the absorption of COS with an MV of 3.8 kDa in vitro and in vivo increased by more than 23 times and 25 times, respectively [35]. Zeng et al. examined the distribution of four chitosan samples with different MWs and DDs in mice after oral administration. The results indicated that the absorbed chitosan was distributed in all tested organs, such as the liver, the kidneys, blood, the spleen, and so on. The concentration of chitosan in blood was much less, while the concentration in the liver was much higher [36]. As for the in vivo metabolism, the analyses were carried out in mice and rats with intraperitoneal administration. The results demonstrated that chitosan and COS are primarily degraded in the liver, the kidneys, plasma, and urine by lysozyme [37]. Hepatic enzymes play a dominant role in the process of degrading and metabolizing chitosan and COS. The final degradation products of chitosan and COS were primarily excreted from the body through the kidney in urine at low MWs [38].

3. Biological Activities of Chitosan and COS

3.1. Antioxidant Activity

The aging of animals is closely related to the oxidative damage caused by free radicals. Many have been confirmed that excessive free radicals in animals that are not cleared in time are an important factor leading to aging and many noncommunicable diseases (e.g., diabetes) [39]. Although free radicals in the body were found to have certain health benefits, such as immunity and signal transduction, too many free radicals will give rise to the denaturation of biological macromolecules, including protein and nucleic acid, which aggravates cell destruction and apoptosis in some pathological states [40]. The body’s ability to scavenge free radicals is limited and weakens with age. Taking exogenous free radical scavengers is an effective method to delay aging and prevent diseases related to it. Therefore, finding edible or pharmaceutic free radical scavengers beneficial to the human body is an urgent concern. Biologically safe chitin derivatives, such as chitosan and COS, are excellent natural antioxidants.

3.2. Anti-Inflammatory Activity

It is well known that immunity refers to the capability of the immune system to distinguish alien and non-alien substances and eliminate antigenic foreign objects through immune responses so as to maintain body homeostasis. Inflammation is a kind of severe immune response, which is the body’s physiological protection from such deleterious stimuli as pathogens and products of tissue injury. Inflammatory responses usually include the production of proinflammatory cytokines (e.g., IL-1β, TNF-α, and IFN-γ) and free radicals and the recruitment and activation of immune cells [41]. In normal physiological states, these inflammatory processes are conductive to the elimination of pathogens and foreign objects, which helps tissue repair and regeneration [42]. However, the inflammatory responses become hyperactive in certain abnormal states. Excessive production of inflammatory factors results in metabolic disorders (e.g., atherosclerosis), tissue damage (e.g., rheumatoid arthritis), and even tumor formation [43]. Chitin derivatives not only exhibit good immune activity, enhancing both innate and adaptive immune systems, but also have excellent anti-inflammatory activity [44][45].
It was supported by animals that supported the anti-inflammatory effect of chitin derivatives, especially COS. In LPS-challenged mice, intraperitoneal administration of COS not only combated oxidative damage but also exerted significant anti-inflammatory activity by reducing neutrophil infiltration in organs and TNF-α and IL-1β in serum [46]. A similar effect was observed in dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) mice model, in which oral administration of COS at a dosage of 10–20 mg/kg/day improved IBD by suppressing the nuclear factor kappa B (NF-κB) signaling pathway and decreasing the levels of TNF-α and IL-6 in colonic tissues [47]. Recently, in another DSS-induced mice model, treatment with chitosan and COS relieved the inflammation caused by ulcerative colitis (UC). The anti-inflammatory effect is characterized by the increased level of anti-inflammatory IL-10, the reduced levels of proinflammatory factors, including IL-1β, IL-6, TNF-α, myeloperoxidase, and inducible nitric oxide synthase (iNOS), as well as the inhibition of the TRL-4/NF-κB/mitogen-activated protein kinase (MAPK) signaling pathway [48]. Additionally, the administration of COS by oral gavage can reduce proinflammatory cytokines, neutrophil infiltration, and macrophage polarization in the liver of HFD-fed mice by the activation of the adenosine-monophosphate-activated protein kinase (AMPK) signaling pathway [49]. Mohyuddin et al. confirmed that oral administration of COS at a dosage of 300–600 mg/kg/day for 7 days relieved the transcriptional downregulation of tight junction proteins Claudin-2 and Occludin in colonic tissue under heat stress in mice. Further analysis displayed that this administration suppressed the production of HSP70, TLR4, p65, TNF-α, and IL-10, indicating an anti-inflammatory ability of COS to tolerate hot environmental conditions [50]. In summary, the anti-inflammatory activity of chitosan and COS is closely related to the regulation of specific signaling pathways mainly including inhibiting NF-κB and MAPK pathways and activating the AMPK pathway.
Over the past decade, the mechanisms underlying the anti-inflammatory activity of COS were explored and enriched especially by in vitro one. Firstly, the study on the mouse RAW 264.7 macrophage cell line demonstrated that COS can block the binding of LPS to TLR4 through competitive binding with TLR4 in order to attenuate the downstream NF-κB and MAPK signaling pathways [51]. This mechanism was also confirmed by the study with intestinal porcine epithelial cells [52]. Secondly, COS can inhibit the nuclear translocation of NF-κB, which attenuates corresponding inflammatory responses. This inhibition can be achieved by suppressing C-Jun-N-terminalkinase (JNK1/2), preventing degradation of inhibitory kappa B (IκB), or reducing OGT (O-GlcNAc transferase)-dependent O-GlcNAcylation of NF-κB [53][54]. Thirdly, in LPS-stimulated RAW 264.7 cells, COS was found to alleviate the inflammatory responses through NF-E2-related factor 2 (Nrf2)/MAPK-mediated induction of heme oxygenase-1 (HO-1) [55]. Additionally, in both LPS-stimulated RAW 264.7 cells and the colonic tissues of DSS-induced colitis mice indicated that COS can upregulate the level of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ directly combines to NF-κB p65, resulting in its ubiquitination and degradation or the increased expression of Sirtuin 1 (SIRT1). SIRT1 is a NAD+-dependent histone deacetylase, which inhibits the activity of NF-κB by deacetylaing Lys310 in NF-κB p65 [56]. Generally, COS can exert an anti-inflammatory effect via the PPARγ/SIRT1-mediated interference with the NF-κB pathway.
Due to the anti-inflammatory activity of Chitosan and COS, they exhibit significant regulatory effect on the glucolipid metabolism. By Bai et al. suggested that in HFD-fed C57BL/6J mice, COS can improve glucolipid metabolism disorder in the liver by inhibiting the transcriptional expression of proinflammatory cytokines, including IL-6, monocyte chemoattractant protein-1 (MCP-1), and TNF-α, as well as upregulating the expression of PPARγ [57]. The effect of ameliorating glucolipid metabolism was also found in a diabetic rat model fed with a diet containing 5% chitosan. The mechanism is related to decreasing plasma TNF-α, insulin resistance, and the activities of alanine aminotransferase (ALT) and adipose tissue lipoprotein lipase by oral administration with chitosan [58]. One of the causes of insulin resistance is attributed to chronic tissue inflammation [59]. Kwon et al. reported that the administration of COS with an MV less than 1.0 kDa exerted antidiabetic effects by significantly reducing hyperglycemia in both animals and humans [60][61][62][63]. Recently, the same team evaluated the antiobesity effect of COS on lipid accumulation and adipogenic gene expression with 3T3-L1 adipocytes and an SD rat model, respectively. The findings suggested that COS may prevent diet-induced weight gain and that the antiobesity effect is mediated partially via inhibiting adipogenesis and increasing adiponectin levels [64]. Obesity, the most common chronic metabolic disease, has been proved to induce low-grade inflammation [65]. What was mentioned above supported the feasibility that COS with anti-inflammatory activity can be applied as a nutraceutical against metabolic diseases such as diabetes and obesity. Meanwhile, COS was found to exhibit an antitumor effect which is largely involved with its anti-inflammatory activity. Muanprasat et al. revealed that oral administration of COS prevented the development of aberrant crypt foci in a mouse model of colitis-associated colorectal cancer (CRC) via a mechanism involving AMPK-activation-induced β-catenin suppression and caspase-3 activation. They further confirmed that COS-induced AMPK activation was probably due to calcium-sensing receptor (CaSR)-phospholipase C (PLC)-IP3-receptor-channel-mediated calcium release from the endoplasmic reticulum (ER) by in vitro experiment with T84 cells [66]. Furthermore, AMPK activation by COS suppressed the NF-κB-mediated inflammatory responses and the mammalian targets of rapamycin (mTOR) signaling [67], the latter of which play important roles in tumor cell proliferation [68]. The anti-inflammatory activity of COS makes it a potential biomaterial which can be applied in the prevention and treatment of CRC and other tumor diseases.

3.3. Antimicrobial Activity

Allan and Hadwiger first reported that chitosan has antifungal activity in 1979, which attracted extensive attention from researchers [69]. So far, many researches have confirmed that chitosan and COS have a broad-spectrum antimicrobial activity on bacteria, fungi, and viruses [70], but are almost nontoxic to healthy mammalians [71][72][73].
It was demonstrated that chitosan and COS showed antibacterial effects on many clinically important Gram-positive and Gram-negative bacteria, especially some pathogenic bacteria, including Escherichia coli, Vibrio parahaemolyticus, Salmonella typhimurium, Pseudomonas aeruginosa, Mycobacterium luteum, Streptococcus mutans, Streptococcus faecalis, Streptococcus epidermidis, Staphylococcus aureus, Listeria monocytogenes, and Yersinia enterocolitica [74][75][76]. There are several mechanisms underlying the antimicrobial activity of chitosan and COS. Firstly, they suppress bacteria via combining with the components with negative charges on the bacterial surface (e.g., peptidoglycans in the cell wall of Gram-positive bacteria or O-antigens of lipopolysaccharide in the outer membrane of Gram-negative bacteria) via their protonated amino group with positive charges at acidic pH. This electrostatic combination of chitosan and COS with bacteria prevents transmembrane transport and also results in damage and leakage of the cell surface [71]. Additionally, the free amino groups of chitosan and COS have a strong ability to chelate the metal ions on the cell surface of bacteria to form complexes, thus preventing the growth of the bacteria by cutting off the supply of minerals [77]. At the same time, this metal-chelating property can obstruct the formation of insoluble calcium phosphate so as to promote the absorption of calcium ions in the small intestine [78]. Moreover, because of low molecular weight, COS and chitosan with low DP can enter the bacterial cell and penetrate the nucleoid. The following binding with DNA interferes with its replication and expression and then destroys the intracellular metabolism of the bacteria [71][77].
These above mechanisms also explain the antifungal activity of chitosan and COS. An organometallic nanoparticle of chitosan conjugated with iron oxide exhibited significant dose-dependent antifungal activity against the phytopathogen Rhizopus oryzae [14]. Chitosan was also proved to suppress other phytopathogenic fungi, including Botrytis cinerea, Phytophthora infestans, Alternaria solani, Fusarium oxysporum, Aspergillus flavus, and Penicillium spp. [79][80]. Likewise, the antifungal activity of COS was analyzed by detecting the minimum inhibitory concentration (MIC). The results showed that COS was effective against Saccharomyces cerevisiae, Aspergillus niger, and Candida species at the concentration of 1.3 to 1.5 mg/mL [32][70][76][81].
Except for the antibacterial and antifungal effects, chitosan and COS also display antiviral ability. For example, chitosan conjugated with thioglycolic acid can be applied as the carrier for the anti-HIV drug tenofovir to promote the body’s absorption of this drug [82]. Moreover, the sulfated COS derivative can combine tightly with the envelope glycoprotein GP120 of HIV-1 to form a complex, which interrupts the interaction between the GP120 and CD4 cell surface receptor and prevents HIV-1 from entering immune cells [83].
Although the antimicrobial activity of chitosan and COS is lower than traditional antibiotics and antifungal drugs, they are still potential and promising antimicrobial agents which can be applied in in the fields of food, medicine, and agriculture due to their valuable biosafety and biocompatibility.

References

  1. Kaur, S.; Dhillon, G.S. The versatile biopolymer chitosan: Potential sources, evaluation of extraction methods and applications. Crit. Rev. Microbiol. 2014, 40, 155–175.
  2. El Knidri, H.; Belaabed, R.; Addaou, A.; Laajeb, A.; Lahsini, A. Extraction, chemical modification and characterization of chitin and chitosan. Int. J. Biol. Macromol. 2018, 120, 1181–1189.
  3. Dhillon, G.S.; Kaur, S.; Brar, S.K.; Verma, M. Green synthesis approach: Extraction of chitosan from fungus mycelia. Crit. Rev. Biotechnol. 2013, 33, 379–403.
  4. Mohan, K.; Ganesan, A.R.; Ezhilarasi, P.N.; Kondamareddy, K.K.; Rajan, D.K.; Sathishkumar, P.; Rajarajeswaran, J.; Conterno, L. Green and eco-friendly approaches for the extraction of chitin and chitosan: A review. Carbohydr. Polym. 2022, 287, 119349.
  5. Younes, I.; Rinaudo, M. Chitin and chitosan preparation from marine sources. Structure, properties and applications. Mar. Drugs 2015, 13, 1133–1174.
  6. Kou, S.G.; Peters, L.M.; Mucalo, M.R. Chitosan: A review of sources and preparation methods. Int. J. Biol. Macromol. 2021, 169, 85–94.
  7. Elieh-Ali-Komi, D.; Hamblin, M.R. Chitin and Chitosan: Production and Application of Versatile Biomedical Nanomaterials. Int. J. Adv. Res. 2016, 4, 411–427.
  8. Saqib, S.; Zaman, W.; Ayaz, A.; Habib, S.; Bahadur, S.; Hussain, S.; Muhammad, S.; Ullah, F. Postharvest disease inhibition in fruit by synthesis and characterization of chitosan iron oxide nanoparticles. Biocatal. Agric. Biotechnol. 2020, 28, 101729.
  9. Riaz Rajoka, M.S.; Mehwish, H.M.; Wu, Y.; Zhao, L.; Arfat, Y.; Majeed, K.; Anwaar, S. Chitin/chitosan derivatives and their interactions with microorganisms: A comprehensive review and future perspectives. Crit. Rev. Biotechnol. 2020, 40, 365–379.
  10. Vakili, M.; Rafatullah, M.; Salamatinia, B.; Abdullah, A.Z.; Ibrahim, M.H.; Tan, K.B.; Gholami, Z.; Amouzgar, P. Application of chitosan and its derivatives as adsorbents for dye removal from water and wastewater: A review. Carbohydr. Polym. 2014, 113, 115–130.
  11. Boamah, P.O.; Huang, Y.; Hua, M.; Zhang, Q.; Wu, J.; Onumah, J.; Sam-Amoah, L.K.; Boamah, P.O. Sorption of heavy metal ions onto carboxylate chitosan derivatives—A mini-review. Ecotoxicol. Environ. Saf. 2015, 116, 113–120.
  12. Abdelmalek, B.E.; Sila, A.; Haddar, A.; Bougatef, A.; Ayadi, M.A. Beta-Chitin and chitosan from squid gladius: Biological activities of chitosan and its application as clarifying agent for apple juice. Int. J. Biol. Macromol. 2017, 104, 953–962.
  13. Arslan, B.; Soyer, A. Effects of chitosan as a surface fungus inhibitor on microbiological, physicochemical, oxidative and sensory characteristics of dry fermented sausages. Meat Sci. 2018, 145, 107–113.
  14. Saqib, S.; Zaman, W.; Ullah, F.; Majeed, I.; Ayaz, A.; Hussain Munis, M.F. Organometallic assembling of chitosan-Iron oxide nanoparticles with their antifungal evaluation againstRhizopus oryzae. Appl. Organomet. Chem. 2019, 33, e5190.
  15. Wang, Z.; Zhang, F.; Yan, Y.; Zhang, Z.; Wang, L.; Qin, C. Lipid-lowering activities of chitosan and its quaternary ammonium salt for the hyperlipidemia rats induced by high-fat diets. Int. J. Biol. Macromol. 2019, 132, 922–928.
  16. Shanmugapriya, K.; Kim, H.; Saravana, P.S.; Chun, B.S.; Kang, H.W. Fabrication of multifunctional chitosan-based nanocomposite film with rapid healing and antibacterial effect for wound management. Int. J. Biol. Macromol. 2018, 118, 1713–1725.
  17. Franca, J.R.; De Luca, M.P.; Ribeiro, T.G.; Castilho, R.O.; Moreira, A.N.; Santos, V.R.; Faraco, A.A. Propolis-based chitosan varnish: Drug delivery, controlled release and antimicrobial activity against oral pathogen bacteria. BMC Complement. Altern. Med. 2014, 14, 478.
  18. Wei, J.; Xue, W.; Yu, X.; Qiu, X.; Liu, Z. pH Sensitive phosphorylated chitosan hydrogel as vaccine delivery system for intramuscular immunization. J. Biomater. Appl. 2017, 31, 1358–1369.
  19. de Souza, R.; Picola, I.P.D.; Shi, Q.; Petronio, M.S.; Benderdour, M.; Fernandes, J.C.; Lima, A.M.F.; Martins, G.O.; Martinez Junior, A.M.; de Oliveira Tiera, V.A.; et al. Diethylaminoethyl-chitosan as an efficient carrier for siRNA delivery: Improving the condensation process and the nanoparticles properties. Int. J. Biol. Macromol. 2018, 119, 186–197.
  20. Cicciu, M.; Fiorillo, L.; Cervino, G. Chitosan Use in Dentistry: A Systematic Review of Recent Clinical Studies. Mar. Drugs 2019, 17, 417.
  21. Babrawala, I.; Prabhuji, M.L.; Karthikeyan, B.V. Using a Composite Graft of Natural 15% Chitosan Gel in the Management of Intrabony Defects: A Case Series. J. Int. Acad. Periodontol. 2019, 21, 4–10.
  22. Sukpaita, T.; Chirachanchai, S.; Suwattanachai, P.; Everts, V.; Pimkhaokham, A.; Ampornaramveth, R.S. In Vivo Bone Regeneration Induced by a Scaffold of Chitosan/Dicarboxylic Acid Seeded with Human Periodontal Ligament Cells. Int. J. Mol. Sci. 2019, 20, 4883.
  23. Taghizadeh, M.; Taghizadeh, A.; Yazdi, M.K.; Zarrintaj, P.; Stadler, F.J.; Ramsey, J.D.; Habibzadeh, S.; Hosseini Rad, S.; Naderi, G.; Saeb, M.R.; et al. Chitosan-based inks for 3D printing and bioprinting. Green Chem. 2022, 24, 62–101.
  24. Wang, W.; Meng, Q.; Li, Q.; Liu, J.; Zhou, M.; Jin, Z.; Zhao, K. Chitosan Derivatives and Their Application in Biomedicine. Int. J. Mol. Sci. 2020, 21, 487.
  25. Fonseca-Santos, B.; Chorilli, M. An overview of carboxymethyl derivatives of chitosan: Their use as biomaterials and drug delivery systems. Mater. Sci. Eng. C Mater. Biol. Appl. 2017, 77, 1349–1362.
  26. Luan, F.; Wei, L.; Zhang, J.; Tan, W.; Chen, Y.; Dong, F.; Li, Q.; Guo, Z. Preparation and Characterization of Quaternized Chitosan Derivatives and Assessment of Their Antioxidant Activity. Molecules 2018, 23, 516.
  27. Sanchez-Salvador, J.L.; Balea, A.; Monte, M.C.; Negro, C.; Blanco, A. Chitosan grafted/cross-linked with biodegradable polymers: A review. Int. J. Biol. Macromol. 2021, 178, 325–343.
  28. Nunes, Y.L.; de Menezes, F.L.; de Sousa, I.G.; Cavalcante, A.L.G.; Cavalcante, F.T.T.; da Silva Moreira, K.; de Oliveira, A.L.B.; Mota, G.F.; da Silva Souza, J.E.; de Aguiar Falcao, I.R.; et al. Chemical and physical Chitosan modification for designing enzymatic industrial biocatalysts: How to choose the best strategy? Int. J. Biol. Macromol. 2021, 181, 1124–1170.
  29. Wang, W.; Xue, C.; Mao, X. Chitosan: Structural modification, biological activity and application. Int. J. Biol. Macromol. 2020, 164, 4532–4546.
  30. Liaqat, F.; Eltem, R. Chitooligosaccharides and their biological activities: A comprehensive review. Carbohydr. Polym. 2018, 184, 243–259.
  31. Lodhi, G.; Kim, Y.S.; Hwang, J.W.; Kim, S.K.; Jeon, Y.J.; Je, J.Y.; Ahn, C.B.; Moon, S.H.; Jeon, B.T.; Park, P.J. Chitooligosaccharide and its derivatives: Preparation and biological applications. BioMed Res. Int. 2014, 2014, 654913.
  32. Naveed, M.; Phil, L.; Sohail, M.; Hasnat, M.; Baig, M.; Ihsan, A.U.; Shumzaid, M.; Kakar, M.U.; Mehmood Khan, T.; Akabar, M.D.; et al. Chitosan oligosaccharide (COS): An overview. Int. J. Biol. Macromol. 2019, 129, 827–843.
  33. Jafari, H.; Bernaerts, K.V.; Dodi, G.; Shavandi, A. Chitooligosaccharides for wound healing biomaterials engineering. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 117, 111266.
  34. Zhou, J.; Harindintwali, J.D.; Yang, W.; Han, M.; Deng, B.; Luan, H.; Zhang, W.; Liu, X.; Yu, X. Engineering of a chitosanase fused to a carbohydrate-binding module for continuous production of desirable chitooligosaccharides. Carbohydr. Polym. 2021, 273, 118609.
  35. Chae, S.Y.; Jang, M.K.; Nah, J.W. Influence of molecular weight on oral absorption of water soluble chitosans. J. Control. Release Off. J. Control. Release Soc. 2005, 102, 383–394.
  36. Zeng, L.; Qin, C.; Wang, W.; Chi, W.; Li, W. Absorption and distribution of chitosan in mice after oral administration. Carbohydr. Polym. 2008, 71, 435–440.
  37. Li, H.; Jiang, Z.; Han, B.; Niu, S.; Dong, W.; Liu, W. Pharmacokinetics and biodegradation of chitosan in rats. J. Ocean Univ. China 2015, 14, 897–904.
  38. Shao, K.; Han, B.; Dong, W.; Song, F.; Liu, W.; Liu, W. Pharmacokinetics and biodegradation performance of a hydroxypropyl chitosan derivative. J. Ocean Univ. China 2015, 14, 888–896.
  39. Halliwell, B.; Gutteridge, J.M.; Cross, C.E. Free radicals, antioxidants, and human disease: Where are we now? J. Lab. Clin. Med. 1992, 119, 598–620.
  40. Halliwell, B. Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence? Lancet 1994, 344, 721–724.
  41. Takeuchi, O.; Akira, S. Pattern recognition receptors and inflammation. Cell 2010, 140, 805–820.
  42. Karin, M.; Clevers, H. Reparative inflammation takes charge of tissue regeneration. Nature 2016, 529, 307–315.
  43. Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell 2010, 140, 883–899.
  44. Zhang, P.; Liu, W.; Peng, Y.; Han, B.; Yang, Y. Toll like receptor 4 (TLR4) mediates the stimulating activities of chitosan oligosaccharide on macrophages. Int. Immunopharmacol. 2014, 23, 254–261.
  45. Moran, H.B.T.; Turley, J.L.; Andersson, M.; Lavelle, E.C. Immunomodulatory properties of chitosan polymers. Biomaterials 2018, 184, 1–9.
  46. Qiao, Y.; Bai, X.F.; Du, Y.G. Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress. Int. Immunopharmacol. 2011, 11, 121–127.
  47. Yousef, M.; Pichyangkura, R.; Soodvilai, S.; Chatsudthipong, V.; Muanprasat, C. Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: Therapeutic efficacy and possible mechanisms of action. Pharmacol. Res. 2012, 66, 66–79.
  48. Mei, Z.; Huang, X.; Zhang, H.; Cheng, D.; Xu, X.; Fang, M.; Hu, J.; Liu, Y.; Liang, Y.; Mei, Y. Chitin derivatives ameliorate DSS-induced ulcerative colitis by changing gut microbiota and restoring intestinal barrier function. Int. J. Biol. Macromol. 2022, 202, 375–387.
  49. Tao, W.; Sun, W.; Liu, L.; Wang, G.; Xiao, Z.; Pei, X.; Wang, M. Chitosan Oligosaccharide Attenuates Nonalcoholic Fatty Liver Disease Induced by High Fat Diet through Reducing Lipid Accumulation, Inflammation and Oxidative Stress in C57BL/6 Mice. Mar. Drugs 2019, 17, 645.
  50. Mohyuddin, S.G.; Qamar, A.; Hu, C.Y.; Chen, S.W.; Wen, J.Y.; Liu, X.X.; Ma, X.B.; Yu, Z.C.; Yong, Y.H.; Wu, L.Y.; et al. Effect of chitosan on blood profile, inflammatory cytokines by activating TLR4/NF-kappaB signaling pathway in intestine of heat stressed mice. Sci. Rep. 2021, 11, 20608.
  51. Qiao, Y.; Ruan, Y.; Xiong, C.; Xu, Q.; Wei, P.; Ma, P.; Bai, X.; Du, Y. Chitosan oligosaccharides suppressant LPS binding to TLR4/MD-2 receptor complex. Carbohydr. Polym. 2010, 82, 405–411.
  52. Shi, L.; Fang, B.; Yong, Y.; Li, X.; Gong, D.; Li, J.; Yu, T.; Gooneratne, R.; Gao, Z.; Li, S.; et al. Chitosan oligosaccharide-mediated attenuation of LPS-induced inflammation in IPEC-J2 cells is related to the TLR4/NF-kappaB signaling pathway. Carbohydr. Polym. 2019, 219, 269–279.
  53. Li, Y.; Liu, H.; Xu, Q.S.; Du, Y.G.; Xu, J. Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-kappaB and endothelial inflammatory response. Carbohydr. Polym. 2014, 99, 568–578.
  54. Kim, J.H.; Kim, Y.S.; Hwang, J.W.; Han, Y.K.; Lee, J.S.; Kim, S.K.; Jeon, Y.J.; Moon, S.H.; Jeon, B.T.; Bahk, Y.Y.; et al. Sulfated chitosan oligosaccharides suppress LPS-induced NO production via JNK and NF-kappaB inactivation. Molecules 2014, 19, 18232–18247.
  55. Hyung, J.H.; Ahn, C.B.; Il Kim, B.; Kim, K.; Je, J.Y. Involvement of Nrf2-mediated heme oxygenase-1 expression in anti-inflammatory action of chitosan oligosaccharides through MAPK activation in murine macrophages. Eur. J. Pharmacol. 2016, 793, 43–48.
  56. Guo, C.; Zhang, Y.; Ling, T.; Zhao, C.; Li, Y.; Geng, M.; Gai, S.; Qi, W.; Luo, X.; Chen, L.; et al. Chitosan Oligosaccharides Alleviate Colitis by Regulating Intestinal Microbiota and PPARgamma/SIRT1-Mediated NF-kappaB Pathway. Mar. Drugs 2022, 20, 96.
  57. Bai, Y.; Zheng, J.; Yuan, X.; Jiao, S.; Feng, C.; Du, Y.; Liu, H.; Zheng, L. Chitosan Oligosaccharides Improve Glucolipid Metabolism Disorder in Liver by Suppression of Obesity-Related Inflammation and Restoration of Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma). Mar. Drugs 2018, 16, 455.
  58. Liu, S.H.; Feng, S.A.; Chiu, C.Y.; Chiang, M.T. Influence of Dietary Chitosan Feeding Duration on Glucose and Lipid Metabolism in a Diabetic Rat Model. Molecules 2021, 26, 5033.
  59. Lumeng, C.N.; Saltiel, A.R. Inflammatory links between obesity and metabolic disease. J. Clin. Investig. 2011, 121, 2111–2117.
  60. Jo, S.H.; Ha, K.S.; Moon, K.S.; Kim, J.G.; Oh, C.G.; Kim, Y.C.; Apostolidis, E.; Kwon, Y.I. Molecular weight dependent glucose lowering effect of low molecular weight Chitosan Oligosaccharide (GO2KA1) on postprandial blood glucose level in SD rats model. Int. J. Mol. Sci. 2013, 14, 14214–14224.
  61. Kim, J.G.; Jo, S.H.; Ha, K.S.; Kim, S.C.; Kim, Y.C.; Apostolidis, E.; Kwon, Y.I. Effect of long-term supplementation of low molecular weight chitosan oligosaccharide (GO2KA1) on fasting blood glucose and HbA1c in db/db mice model and elucidation of mechanism of action. BMC Complement. Altern. Med. 2014, 14, 272.
  62. Jo, S.-H.; Ha, K.-S.; Lee, J.-W.; Kim, Y.-C.; Apostolidis, E.; Kwon, Y.-I. The reduction effect of low molecular weight chitosan oligosaccharide (GO2KA1) on postprandial blood glucose levels in healthy individuals. Food Sci. Biotechnol. 2014, 23, 971–973.
  63. Kim, H.J.; Ahn, H.Y.; Kwak, J.H.; Shin, D.Y.; Kwon, Y.I.; Oh, C.G.; Lee, J.H. The effects of chitosan oligosaccharide (GO2KA1) supplementation on glucose control in subjects with prediabetes. Food Funct. 2014, 5, 2662–2669.
  64. Lee, J.Y.; Kim, T.Y.; Kang, H.; Oh, J.; Park, J.W.; Kim, S.C.; Kim, M.; Apostolidis, E.; Kim, Y.C.; Kwon, Y.I. Anti-Obesity and Anti-Adipogenic Effects of Chitosan Oligosaccharide (GO2KA1) in SD Rats and in 3T3-L1 Preadipocytes Models. Molecules 2021, 26, 331.
  65. Chen, H.; Sun, L.; Feng, L.; Yin, Y.; Zhang, W. Role of Innate lymphoid Cells in Obesity and Insulin Resistance. Front. Endocrinol. 2022, 13, 855197.
  66. Muanprasat, C.; Wongkrasant, P.; Satitsri, S.; Moonwiriyakit, A.; Pongkorpsakol, P.; Mattaveewong, T.; Pichyangkura, R.; Chatsudthipong, V. Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders. Biochem. Pharmacol. 2015, 96, 225–236.
  67. Mattaveewong, T.; Wongkrasant, P.; Chanchai, S.; Pichyangkura, R.; Chatsudthipong, V.; Muanprasat, C. Chitosan oligosaccharide suppresses tumor progression in a mouse model of colitis-associated colorectal cancer through AMPK activation and suppression of NF-kappaB and mTOR signaling. Carbohydr. Polym. 2016, 145, 30–36.
  68. Faller, W.J.; Jackson, T.J.; Knight, J.R.; Ridgway, R.A.; Jamieson, T.; Karim, S.A.; Jones, C.; Radulescu, S.; Huels, D.J.; Myant, K.B.; et al. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 2015, 517, 497–500.
  69. Carolyn Allan, L.H. Fungicidal effect of chitosan on fungi of varying cell wall composition. Exp. Mycol. 1979, 3, 285–287.
  70. Muanprasat, C.; Chatsudthipong, V. Chitosan oligosaccharide: Biological activities and potential therapeutic applications. Pharmacol. Ther. 2017, 170, 80–97.
  71. Sahariah, P.; Masson, M. Antimicrobial Chitosan and Chitosan Derivatives: A Review of the Structure-Activity Relationship. Biomacromolecules 2017, 18, 3846–3868.
  72. Francois, I.E.; Lescroart, O.; Veraverbeke, W.S.; Kubaszky, R.; Hargitai, J.; Esdaile, D.J.; Beres, E.; Soni, M.G.; Cockburn, A.; Broekaert, W.F. Safety assessment of a wheat bran extract containing arabinoxylan-oligosaccharides: Mutagenicity, clastogenicity, and 90-day rat-feeding studies. Int. J. Toxicol. 2010, 29, 479–495.
  73. Qin, C.; Gao, J.; Wang, L.; Zeng, L.; Liu, Y. Safety evaluation of short-term exposure to chitooligomers from enzymic preparation. Food Chem. Toxicol. 2006, 44, 855–861.
  74. Kim, S.; Rajapakse, N. Enzymatic production and biological activities of chitosan oligosaccharides (COS): A review. Carbohydr. Polym. 2005, 62, 357–368.
  75. Kittur, F.S.; Vishu Kumar, A.B.; Varadaraj, M.C.; Tharanathan, R.N. Chitooligosaccharides—Preparation with the aid of pectinase isozyme from Aspergillus niger and their antibacterial activity. Carbohydr. Res. 2005, 340, 1239–1245.
  76. Wang, Y.; Zhou, P.; Yu, J.; Pan, X.; Wang, P.; Lan, W.; Tao, S. Antimicrobial effect of chitooligosaccharides produced by chitosanase from Pseudomonas CUY8. Asia Pac. J. Clin. Nutr. 2007, 16 (Suppl. 1), 174–177.
  77. Rabea, E.I.; Badawy, M.E.; Stevens, C.V.; Smagghe, G.; Steurbaut, W. Chitosan as antimicrobial agent: Applications and mode of action. Biomacromolecules 2003, 4, 1457–1465.
  78. Jung, W.K.; Moon, S.H.; Kim, S.K. Effect of chitooligosaccharides on calcium bioavailability and bone strength in ovariectomized rats. Life Sci. 2006, 78, 970–976.
  79. Cheung, R.C.; Ng, T.B.; Wong, J.H.; Chan, W.Y. Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications. Mar. Drugs 2015, 13, 5156–5186.
  80. Gabriel Jdos, S.; Tiera, M.J.; Tiera, V.A. Synthesis, Characterization, and Antifungal Activities of Amphiphilic Derivatives of Diethylaminoethyl Chitosan against Aspergillus flavus. J. Agric. Food Chem. 2015, 63, 5725–5731.
  81. Seyfarth, F.; Schliemann, S.; Elsner, P.; Hipler, U.C. Antifungal effect of high- and low-molecular-weight chitosan hydrochloride, carboxymethyl chitosan, chitosan oligosaccharide and N-acetyl-D-glucosamine against Candida albicans, Candida krusei and Candida glabrata. Int. J. Pharm. 2008, 353, 139–148.
  82. Meng, J.; Zhang, T.; Agrahari, V.; Ezoulin, M.J.; Youan, B.B. Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention. Nanomedicine 2014, 9, 1595–1612.
  83. Artan, M.; Karadeniz, F.; Karagozlu, M.Z.; Kim, M.M.; Kim, S.K. Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides. Carbohydr. Res. 2010, 345, 656–662.
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Subjects: Food Science & Technology
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