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Open Access

Sulfated Cyclocarya paliurus polysaccharides exert immunomodulatory potential on macrophages via Toll-like receptor 4 mediated MAPK/NF-κB signaling pathways

Yue Yua,b, Haibin Zhua,b, Mingyue Shena, Qiang Yua,b, Yi Chena, Shiru Moa,b, Jianhua Xiea,b( )
State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
International Institute of Food Innovation, Nanchang University, Nanchang 330200, China

Peer review under responsibility of Tsinghua University Press.

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Highlights

• Sulfated polysaccharides (SCP3) showed favorable immunomodulatory activity.

•SCP3 activates cellular downstream signaling pathways by increasing ROS production.

• SCP3 promotes the secretion of cytokines and NO to regulate immune activity.

• SCP3 induced macrophages activation by TLR4-mediated MAPK/NF-κB signaling pathway.

Graphical Abstract

Abstract

The biological activity of plant polysaccharides can be enhanced by sulfated modification. In this study, the immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides (SCP3) on macrophages RAW264.7 and its potential molecular mechanism were investigated. Results showed that SCP3 at 25−100 μg/mL increased viability and improved phagocytosis of RAW264.7 cells. Meanwhile, SCP3 could activate mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, which increased the phosphorylation of Erk1/2, JNK, p38 and NF-κB p65, promoting secretion of cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and nitric oxide (NO) as well as the production of reactive oxygen species (ROS). In addition, Toll-like receptor 4 (TLR4) receptor inhibitors were able to block the production of NO and TNF-α by SCP3-stimulated macrophages. Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways, the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-α and NO production via TLR4-mediated MAPK and NF-κB pathways. In summary, SCP3 has significant immunomodulatory potential. The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production, which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.

Keywords

Cyclocarya paliurusSulfated polysaccharidesMacrophagesImmunomodulatoryMechanism

References

[1]

M.I.D. Moraes-Pinto, F. Suano-Souza, C.S. Aranda, Immune system: development and acquisition of immunological competence, J. Pediatr. 97(2021) S59-S66. https://doi.org/10.1016/j.jped.2020.10.006.
Crossref Google Scholar
[2]

L. Han, J. Yu, Y. Chen, et al., Immunomodulatory activity of docosahexenoic acid on RAW264.7 cells activation through GPR120-mediated signaling pathway, J. Agric. Food Chem. 66 (2018) 926-934. https://doi.org/10.1021/acs.jafc.7b05894.
Crossref Google Scholar
[3]

Y. Yu, M.Y. Shen, Q.Q. Song, et al., Biological activities and pharmaceutical applications of polysaccharide from natural resources: a review, Carbohydr. Polym. 183 (2018) 91-101. https://doi.org/10.1016/j.carbpol.2017.12.009.
Crossref Google Scholar
[4]

P. Shao, J.R. Feng, P.L. Sun, et al., Recent advances in improving stability of food emulsion by plant polysaccharides, Food Res. Int. 137 (2020) 109376. https://doi.org/10.1016/j.foodres.2020.109376.
Crossref Google Scholar
[5]

P.R. Taylor, L. Martinez-Pomares, M. Stacey, et al., Macrophage receptors and immune recognition, Annu. Rev. Immunol. 23 (2005) 901-944. https://doi.org/10.1146/annurev.immunol.23.021704.115816.
Crossref Google Scholar
[6]

K. Takeda, T. Kaisho, S. Akira, Toll-like receptors, Annu. Rev. Immunol. 21 (2003) 335-376. https://doi.org/10.1146/annurev.immunol.21.120601.141126.
Crossref Google Scholar
[7]

T. Nakamura, H. Suzuki, Y. Wada, et al., Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-κB-dependent signaling pathways through macrophage scavenger receptors, B Biochem. Biophys. Res. Commun. 343 (2006) 286-294. https://doi.org/10.1016/j.bbrc.2006.02.146.
Crossref Google Scholar
[8]

Y. Pu, Z. Liu, C. Zhong, et al., Immunomodulatory effects of a polysaccharide from Solanum nigrum Linne through TLR4-MyD88 signaling pathway, Int. Immunopharmacol. 88 (2020) 106973. https://doi.org/10.1016/j.intimp.2020.106973.
Crossref Google Scholar
[9]

M.J. Park, H.S. Ryu, J.S. Kim, et al., Platycodon grandiflorum polysaccharide induces dendritic cell maturation via TLR4 signaling, Food Chem. Toxicol. 72 (2014) 212-220. https://doi.org/10.1016/j.fct.2014.07.011.
Crossref Google Scholar
[10]

X. Li, W. Xu, TLR4-mediated activation of macrophages by the polysaccharide fraction from Polyporus umbellatus (pers.) Fries, J. Ethnopharmacol. 135 (2011) 1-6. https://doi.org/10.1016/j.jep.2010.06.028.
Crossref Google Scholar
[11]

M. Wang, X.B. Yang, J.W. Zhao, et al., Structural characterization and macrophage immunomodulatory activity of a novel polysaccharide from Smilax glabra Roxb, Carbohydr. Polym. 156 (2017) 390-402. https://doi.org/10.1016/j.carbpol.2016.09.033.
Crossref Google Scholar
[12]

M. Hayden, S. Ghosh, NF-κB in immunobiology, Cell Res. 21 (2011) 223-244. https://doi.org/10.1038/cr.2011.13.
Crossref Google Scholar
[13]

S. Feng, H. Ding, L. Liu, et al., Astragalus polysaccharide enhances the immune function of RAW264.7 macrophages via the NF-κB p65/MAPK signaling pathway, Exp. Ther. Med. 21 (2021) 1. https://doi.org/10.3892/etm.2020.9452.
Crossref Google Scholar
[14]

M. Alavi, M. Tabarsa, S. You, et al., Structural characteristics, molecular properties and immunostimulatory effects of sulfated polysaccharide from freshwater Myriophyllum spicatum L, Int. J. Biol. Macromol. 153 (2020) 951-961. https://doi.org/10.1016/j.ijbiomac.2019.11.109.
Crossref Google Scholar
[15]

J.Y. Wang, H.L. Zhang, H.L. Wang, et al., An immunomodulatory polysaccharide from blackberry seeds and its action on RAW264.7 cells via activation of NF-κB/MAPK pathways, Food Agr. Immunol. 31 (2020) 575-586. https://doi.org/10.1080/09540105.2020.1747407.
Crossref Google Scholar
[16]

J.H. Xie, C.J. Dong, S.P. Nie, et al., Extraction, chemical composition and antioxidant activity of flavonoids from Cyclocarya paliurus (Batal.) Iljinskaja leaves, Food Chem. 186 (2015) 97-105. https://doi.org/10.1016/j.foodchem.2014.06.106.
Crossref Google Scholar
[17]

J.H. Xie, X. Liu, M.Y. Shen, et al., Purification, physicochemical characterisation and anticancer activity of a polysaccharide from Cyclocarya paliurus leaves, Food Chem. 136 (2013) 1453-1460. https://doi.org/10.1016/j.foodchem.2012.09.078.
Crossref Google Scholar
[18]

L. Xiong, K.H. Ouyang, H. Chen, et al., Immunomodulatory effect of Cyclocarya paliurus polysaccharide in cyclophosphamide induced immunocompromised mice, Bioact. Carbohydr. Diet. Fibre 24 (2020) 100224. https://doi.org/10.1016/j.bcdf.2020.100224.
Crossref Google Scholar
[19]

T. Wu, M. Shen, X. Guo, et al., Cyclocarya paliurus polysaccharide alleviates liver inflammation in mice via beneficial regulation of gut microbiota and TLR4/MAPK signaling pathways, Int. J. Biol. Macromol. 160 (2020) 164-174. https://doi.org/10.1016/j.ijbiomac.2020.05.187.
Crossref Google Scholar
[20]

Y. Yu, H.B. Zhu, M.Y. Shen, et al., Sulfation modification enhances the intestinal regulation of Cyclocarya paliurus polysaccharides in cyclophosphamide-treated mice via restoring intestinal mucosal barrier function and modulating gut microbiota, Food Funct. 12 (2021) 12278-12290. https://doi.org/10.1039/D1FO03042F.
Crossref Google Scholar
[21]

Y. Jing, J. Zhu, T. Liu, et al., Structural characterization and biological activities of a novel polysaccharide from cultured Cordyceps militaris and its sulfated derivative, J. Agric. Food Chem. 63 (2015) 3464-3471. https://doi.org/10.1021/jf505915t.
Crossref Google Scholar
[22]

F. Cardozo, I. Larsen, E. Carballo, et al., In vivo anti-herpes simplex virus activity of a sulfated derivative of Agaricus brasiliensis mycelial polysaccharide, Antimicrob. Agents Chemother. 57 (2013) 2541-2549. https://doi.org/10.1128/AAC.02250-12.
Crossref Google Scholar
[23]

Y. Han, K. Ouyang, J. Li, et al., Sulfated modification, characterization, immunomodulatory activities and mechanism of the polysaccharides from Cyclocarya paliurus on dendritic cells, Int. J. Biol. Macromol. 159 (2020) 108-116. https://doi.org/10.1016/j.ijbiomac.2020.04.265.
Crossref Google Scholar
[24]

Y. Yu, Q.Q. Song, L.X. Huang, et al., Immunomodulatory activities of sulfated Cyclocarya paliurus polysaccharides with different degrees of substitution on mouse spleen lymphocytes, J. Funct. Food 64 (2020) 103706. https://doi.org/10.1016/j.jff.2019.103706.
Crossref Google Scholar
[25]

Y. Yu, S.R. Mo, M.Y. Shen, et al., Sulfated modification enhances the immunomodulatory effect of Cyclocarya paliurus polysaccharide on cyclophosphamide-induced immunosuppressed mice through MyD88-dependent MAPK/NF-κB and PI3K-Akt signaling pathways, Food Res. Int. 150 (2021) 110756. https://doi.org/10.1016/j.foodres.2021.110756.
Crossref Google Scholar
[26]

D.D. Wang, W.J. Pan, S. Mehmood, et al., Polysaccharide isolated from Sarcodon aspratus induces RAW264.7 activity via TLR4-mediated NF-κB and MAPK signaling pathways, Int. J. Biol. Macromol. 120 (2018) 1039-1047. https://doi.org/10.1016/j.ijbiomac.2018.08.147.
Crossref Google Scholar
[27]

G.M. Jose, M. Raghavankutty, G.M. Kurup, Sulfated polysaccharides from Padina tetrastromatica induce apoptosis in HeLa cells through ROS triggered mitochondrial pathway, Process Biochem. 68 (2018) 197-204. https://doi.org/10.1016/j.procbio.2018.02.014.
Crossref Google Scholar
[28]

W. Wang, Y. Zou, Q. Li, et al., Immunomodulatory effects of a polysaccharide purified from Lepidium meyenii Walp. on macrophages, Process Biochem. 51 (2016) 542-553. https://doi.org/10.1016/j.procbio.2016.01.003.
Crossref Google Scholar
[29]

J.Y. Wang, H.L. Wang, H.L. Zhang, et al., Immunomodulation of ADPs-1a and ADPs-3a on RAW264.7 cells through NF-κB/MAPK signaling pathway, Int. J. Biol. Macromol. 132 (2019) 1024-1030. https://doi.org/10.1016/j.ijbiomac.2019.04.031.
Crossref Google Scholar
[30]

Y.Z. Hong, M.Y. Shen, L.X. Huang, et al., Mesona chinensis Benth polysaccharides alleviates liver injury by beneficial regulation of gut microbiota in cyclophosphamide-induced mice, Food Sci. Hum. Wellness 11(2022) 74-84. https://doi.org/10.1016/j.fshw.2021.07.009.
Crossref Google Scholar
[31]

M.Y. Shen, X.X. Chen, L.X. Huang, et al, Sulfated Mesona chinensis Benth polysaccharide enhance the immunomodulatory activities of cyclophosphamide-treated mice, J. Funct. Food 76 (2021) 104321. https://doi.org/10.1016/j.jff.2020.104321.
Crossref Google Scholar
[32]

M. Cho, D.J. Lee, J.K. Kim, et al., Molecular characterization and immunomodulatory activity of sulfated fucans from Agarum cribrosum, Carbohydr. Polym. 113 (2014) 507-514. https://doi.org/10.1016/j.carbpol.2014.07.055.
Crossref Google Scholar
[33]

W. Chen, W. Zhang, W. Shen, et al., Effects of the acid polysaccharide fraction isolated from a cultivated Cordyceps sinensis on macrophages in vitro, Cell Immunol. 262 (2010) 69-74. https://doi.org/10.1016/j.cellimm.2010.01.001.
Crossref Google Scholar
[34]

J. Wang, Y. Hu, D. Wang, et al., Sulfated modification can enhance the immune-enhancing activity of lycium barbarum polysaccharides, Cell. Immunol. 263 (2010) 219-223. https://doi.org/10.1016/j.cellimm.2010.04.001.
Crossref Google Scholar
[35]

Y. Zhang, S. Choksi, K. Chen, et al., ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages, Cell Res. 23 (2013) 898-914. https://doi.org/10.1038/cr.2013.75.
Crossref Google Scholar
[36]

E. Rendra, V. Riabov, D.M. Mossel, et al., Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology 224(2019) 242-253. https://doi.org/10.1016/j.imbio.2018.11.010.
Crossref Google Scholar
[37]

Q. Yu, S.P. Nie, J.Q. Wang, et al., Toll-like receptor 4-mediated ROS signaling pathway involved in Ganoderma atrum polysaccharide-induced tumor necrosis factor-α secretion during macrophage activation, Food Chem. Toxicol. 66 (2014) 14-22. https://doi.org/10.1016/j.fct.2014.01.018.
Crossref Google Scholar
[38]

M. Yin, Y. Zhang, H. Li, Advances in research on immunoregulation of macrophages by plant polysaccharides, Front. Immunol. 10 (2019) 145. https://doi.org/10.3389/fimmu.2019.00145.
Crossref Google Scholar
[39]

M.S. Shin, S.B. Park, K.S. Shin, Molecular mechanisms of immunomodulatory activity by polysaccharide isolated from the peels of Citrus unshiu, Int. J. Biol. Macromol. 112 (2018) 576-583. https://doi.org/10.1016/j.ijbiomac.2018.02.006.
Crossref Google Scholar
[40]

Y. Xie, L. Wang, H. Sun, et al., A polysaccharide extracted from alfalfa activates splenic B cells by TLR4 and acts primarily via the MAPK/p38 pathway, Food Funct. 11 (2020) 9035-9047. https://doi.org/10.1039/D0FO01711F.
Crossref Google Scholar
[41]

Y. Cai, P. Chen, C. Wu, et al., Sulfated modification and biological activities of polysaccharides derived from Zizyphus jujuba cv. Jinchangzao, Int. J. Biol. Macromol. 120 (2018) 1149-1155. https://doi.org/10.1016/j.ijbiomac.2018.08.141.
Crossref Google Scholar
[42]

S.S. Ferreira, C.P. Passos, P. Madureira, et al., Structure-function relationships of immunostimulatory polysaccharides: a review, Carbohydr. Polym. 132 (2015) 378-396. https://doi.org/10.1016/j.carbpol.2015.05.079.
Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 1,
January 2024
Pages 115-123
DOI: 10.26599/FSHW.2022.9250009
Cite this article:
Yu Y, Zhu H, Shen M, et al. Sulfated Cyclocarya paliurus polysaccharides exert immunomodulatory potential on macrophages via Toll-like receptor 4 mediated MAPK/NF-κB signaling pathways. Food Science and Human Wellness, 2024, 13(1): 115-123. https://doi.org/10.26599/FSHW.2022.9250009

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Received: 25 March 2022
Revised: 10 April 2022
Accepted: 19 April 2022
Published: 01 June 2023
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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