Identification of intracellular activation mechanism of rhamnogalacturonan-I type polysaccharide purified from Panax ginseng leaves in macrophages and roles of component sugar chains on activity.

Macrophage Panax ginseng Rhamnogalacturonan-I Structure-activity relationship

Journal

Journal of natural medicines
ISSN: 1861-0293
Titre abrégé: J Nat Med
Pays: Japan
ID NLM: 101518405

Informations de publication

Date de publication:
28 Dec 2023
Historique:
received: 19 08 2023
accepted: 27 11 2023
medline: 28 12 2023
pubmed: 28 12 2023
entrez: 28 12 2023
Statut: aheadofprint

Résumé

This study aimed to investigate the mechanisms underlying intracellular signaling pathways in macrophages in relation to the structural features of rhamnogalacturonan (RG) I-type polysaccharide (PGEP-I) purified from Panax ginseng leaves. For this investigation, we used several specific inhibitors and antibodies against mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and pattern recognition receptors (PRRs). Furthermore, we investigated the roles of component sugar chains on immunostimulating activity through a sequential enzymatic and chemical degradation steps. We found that PGEP-I effectively induced the phosphorylation of several MAPK- and NF-κB-related proteins, such as p38, cJun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p65. Particularly, immunocytochemistry analysis confirmed the PGEP-I-induced translocation of p65 into the nucleus. Furthermore, the breakdown of PGEP-I side chains and main chain during sequential enzymatic and chemical degradation reduced the PGEP-I-induced macrophage cytokine secretion activity. IL-6, TNF-α, and NO secreted by macrophages are associated with several signaling pathway proteins such as ERK, JNK, and NF-κB and several PRRs such as dectin-1, CD11b, CD14, TLR2, TLR4, and SR. Thus, these findings suggest that PGEP-I exerts potent macrophage-activating effects, which can be attributed to its typical RG-I structure comprising arabinan, type II arabinogalactan, and rhamnose-galacturonic acid repeating units in the main chain.

Identifiants

pubmed: 38153587
doi: 10.1007/s11418-023-01768-w
pii: 10.1007/s11418-023-01768-w
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.

Références

Jiang M-H, Zhu L, Jiang J-G (2010) Immunoregulatory actions of polysaccharides from Chinese herbal medicine. Expert Opin Ther Targets 14:1367–1402. https://doi.org/10.1517/14728222.2010.531010
doi: 10.1517/14728222.2010.531010 pubmed: 21058924
Leung M, Liu C, Koon J, Fung K (2006) Polysaccharide biological response modifiers. Immunol Lett 105:101–114. https://doi.org/10.1016/j.imlet.2006.01.009
doi: 10.1016/j.imlet.2006.01.009 pubmed: 16554097
Liu J, Willför S, Xu C (2015) A review of bioactive plant polysaccharides: biological activities, functionalization, and biomedical applications. Bioact Carbohydr Diet Fibre 5:31–61. https://doi.org/10.1016/j.bcdf.2014.12.001
doi: 10.1016/j.bcdf.2014.12.001
Yin M, Zhang Y, Li H (2019) Advances in research on immunoregulation of macrophages by plant polysaccharides. Front Immunol 10:145. https://doi.org/10.3389/fimmu.2019.00145
doi: 10.3389/fimmu.2019.00145 pubmed: 30804942 pmcid: 6370632
Yu Y, Shen M, Song Q, Xie J (2018) Biological activities and pharmaceutical applications of polysaccharide from natural resources: a review. Carbohydr Polym 183:91–101. https://doi.org/10.1016/j.carbpol.2017.12.009
doi: 10.1016/j.carbpol.2017.12.009 pubmed: 29352896
Voragen AG, Coenen G-J, Verhoef RP, Schols HA (2009) Pectin, a versatile polysaccharide present in plant cell walls. Struct Chem 20:263–275. https://doi.org/10.1007/s11224-009-9442-z
doi: 10.1007/s11224-009-9442-z
Mohnen D (2008) Pectin structure and biosynthesis. Curr Opin Plant Biol 11:266–277. https://doi.org/10.1016/j.pbi.2008.03.006
doi: 10.1016/j.pbi.2008.03.006 pubmed: 18486536
Yapo BM (2011) Rhamnogalacturonan-I: a structurally puzzling and functionally versatile polysaccharide from plant cell walls and mucilages. Polym Rev 51:391–413. https://doi.org/10.1080/15583724.2011.615962
doi: 10.1080/15583724.2011.615962
Ishii T, Matsunaga T (2001) Pectic polysaccharide rhamnogalacturonan II is covalently linked to homogalacturonan. Phytochemistry 57:969–974. https://doi.org/10.1016/S0031-9422(01)00047-4
doi: 10.1016/S0031-9422(01)00047-4 pubmed: 11423143
Park H-R, Park SB, Hong H-D, Suh HJ, Shin K-S (2017) Structural elucidation of anti-metastatic rhamnogalacturonan II from the pectinase digest of citrus peels (Citrus unshiu). Int J Biol Macromol 94:161–169. https://doi.org/10.1016/j.ijbiomac.2016.09.100
doi: 10.1016/j.ijbiomac.2016.09.100 pubmed: 27693835
Yue F, Xu J, Zhang S, Hu X, Wang X, Lü X (2022) Structural features and anticancer mechanisms of pectic polysaccharides: a review. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2022.04.073
doi: 10.1016/j.ijbiomac.2022.04.073 pubmed: 36592855
Li N, Wang C, Georgiev MI, Bajpai VK, Tundis R, Simal-Gandara J, Lu X, Xiao J, Tang X, Qiao X (2021) Advances in dietary polysaccharides as anticancer agents: structure–activity relationship. Trends Food Sci Technol 111:360–377. https://doi.org/10.1016/j.tifs.2021.03.008
doi: 10.1016/j.tifs.2021.03.008
Maria-Ferreira D, Dallazen JL, Corso CR, Nascimento AM, Cipriani TR, da Silva Watanabe P, Sant’Ana DMG, Baggio CH, de Paula Werner MF (2021) Rhamnogalacturonan polysaccharide inhibits inflammation and oxidative stress and alleviates visceral pain. J Funct Foods 82:104483. https://doi.org/10.1016/j.jff.2021.104483
doi: 10.1016/j.jff.2021.104483
Sun L, Ropartz D, Cui L, Shi H, Ralet M-C, Zhou Y (2019) Structural characterization of rhamnogalacturonan domains from Panax ginseng CA Meyer. Carbohydr Polym 203:119–127. https://doi.org/10.1016/j.carbpol.2018.09.045
doi: 10.1016/j.carbpol.2018.09.045 pubmed: 30318195
Merheb R, Abdel-Massih RM, Karam MC (2019) Immunomodulatory effect of natural and modified Citrus pectin on cytokine levels in the spleen of BALB/c mice. Int J Biol Macromol 121:1–5. https://doi.org/10.1016/j.ijbiomac.2018.09.189
doi: 10.1016/j.ijbiomac.2018.09.189 pubmed: 30292091
Kwak B-S, Hwang D, Lee SJ, Choi H-J, Park H-Y, Shin K-S (2019) Rhamnogalacturonan-I-type polysaccharide purified from broccoli exerts anti-metastatic activities via innate immune cell activation. J Med Food 22:451–459. https://doi.org/10.1089/jmf.2018.4286
doi: 10.1089/jmf.2018.4286 pubmed: 30897013
Birk R, Gratchev A, Hakiy N, Politz O, Schledzewski K, Guillot P, Orfanos C, Goerdt S (2001) Alternative Aktivierung antigenpräsentierender Zellen Konzept und klinische Bedeutung: Konzept und klinische Bedeutung. Hautarzt 52:193–200. https://doi.org/10.1007/s001050051289
doi: 10.1007/s001050051289 pubmed: 11284063
Wu F, Zhou C, Zhou D, Ou S, Huang H (2017) Structural characterization of a novel polysaccharide fraction from Hericium erinaceus and its signaling pathways involved in macrophage immunomodulatory activity. J Funct Foods 37:574–585. https://doi.org/10.1016/j.jff.2017.08.030
doi: 10.1016/j.jff.2017.08.030
Galli G, Saleh M (2021) Immunometabolism of macrophages in bacterial infections. Front Cell Infect Microbiol 10:607650. https://doi.org/10.3389/fcimb.2020.607650
doi: 10.3389/fcimb.2020.607650 pubmed: 33585278 pmcid: 7879570
Deng C, Fu H, Shang J, Chen J, Xu X (2018) Dectin-1 mediates the immunoenhancement effect of the polysaccharide from Dictyophora indusiata. Int J Biol Macromol 109:369–374. https://doi.org/10.1016/j.ijbiomac.2017.12.113
doi: 10.1016/j.ijbiomac.2017.12.113 pubmed: 29274416
Wang C-L, Lu C-Y, Pi C-C, Zhuang Y-J, Chu C-L, Liu W-H, Chen C-J (2012) Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors. BMC Complement Altern Med 12:1–10. https://doi.org/10.1186/1472-6882-12-119
doi: 10.1186/1472-6882-12-119
Liu Y, Shepherd EG, Nelin LD (2007) MAPK phosphatases—regulating the immune response. Nat Rev Immunol 7:202–212. https://doi.org/10.1038/nri2035
doi: 10.1038/nri2035 pubmed: 17318231
Rao KMK (2001) MAP kinase activation in macrophages. J Leukoc Biol 69:3–10. https://doi.org/10.1189/jlb.69.1.3
doi: 10.1189/jlb.69.1.3 pubmed: 11200064
Liu T, Zhang L, Joo D, Sun S-C (2017) NF-κB signaling in inflammation. Signal Transduct Target Ther 2:1–9. https://doi.org/10.1038/sigtrans.2017.23
doi: 10.1038/sigtrans.2017.23
Son S-U, Lee HW, Shin K-S (2023) Immunostimulating activities and anti-cancer efficacy of rhamnogalacturonan-I rich polysaccharide purified from Panax ginseng leaf. Food Biosci 53:102618. https://doi.org/10.1016/j.fbio.2023.102618
doi: 10.1016/j.fbio.2023.102618
Son S-U, Lee SJ, Shin K-S (2022) Immunostimulating and intracellular signaling pathways mechanism on macrophage of rhamnogalacturonan-I type polysaccharide purified from radish leaves. Int J Biol Macromol 217:506–514. https://doi.org/10.1016/j.ijbiomac.2022.07.084
doi: 10.1016/j.ijbiomac.2022.07.084 pubmed: 35843395
Kim HW, Shin M-S, Lee SJ, Park H-R, Jee HS, Yoon TJ, Shin K-S (2019) Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley. Int J Biol Macromol 131:1084–1091. https://doi.org/10.1016/j.ijbiomac.2019.03.159
doi: 10.1016/j.ijbiomac.2019.03.159 pubmed: 30914368
Lasunskaia EB, Campos MN, de Andrade MR, DaMatta RA, Kipnis TL, Einicker-Lamas M, Da Silva WD (2006) Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling. J Leukoc Biol 80:1480–1490. https://doi.org/10.1189/jlb.0106066
doi: 10.1189/jlb.0106066 pubmed: 17005905
van Holst G-J, Clarke AE (1985) Quantification of arabinogalactan-protein in plant extracts by single radial gel diffusion. Anal Biochem 148:446–450. https://doi.org/10.1016/0003-2697(85)90251-9
doi: 10.1016/0003-2697(85)90251-9 pubmed: 3933380
Son S-U, Lee SJ, Choi EH, Shin K-S (2022) Clarification of the structural features of Rhamnogalacturonan-I type polysaccharide purified from radish leaves. Int J Biol Macromol 209:923–934. https://doi.org/10.1016/j.ijbiomac.2022.04.045
doi: 10.1016/j.ijbiomac.2022.04.045 pubmed: 35447261
Nosaka M, Ishida Y, Kimura A, Kuninaka Y, Taruya A, Ozaki M, Tanaka A, Mukaida N, Kondo T (2020) Crucial involvement of IL-6 in thrombus resolution in mice via macrophage recruitment and the induction of proteolytic enzymes. Front Immunol 10:3150. https://doi.org/10.3389/fimmu.2019.03150
doi: 10.3389/fimmu.2019.03150 pubmed: 32117207 pmcid: 7019028
Wang KS, Frank DA, Ritz J (2000) Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4. Blood 95:3183–3190. https://doi.org/10.1182/blood.V95.10.3183
doi: 10.1182/blood.V95.10.3183 pubmed: 10807786
Cavalcanti YVN, Brelaz MCA, Neves JKAL, Ferraz JC, Pereira VRA (2012) Role of TNF-alpha, IFN-gamma, and IL-10 in the development of pulmonary tuberculosis. Pulm Med 2012:745483. https://doi.org/10.1155/2012/745483
doi: 10.1155/2012/745483 pubmed: 23251798 pmcid: 3515941
Kounsar F, Rather MA, Ganai BA, Zargar MA (2011) Immuno-enhancing effects of the herbal extract from Himalayan rhubarb Rheum emodi Wall. ex Meissn. Food Chem 126:967–971. https://doi.org/10.1016/j.foodchem.2010.11.103
doi: 10.1016/j.foodchem.2010.11.103
Shen C-Y, Zhang W-L, Jiang J-G (2017) Immune-enhancing activity of polysaccharides from Hibiscus sabdariffa Linn. via MAPK and NF-kB signaling pathways in RAW264. 7 cells. J Funct Foods 34:118–129. https://doi.org/10.1016/j.jff.2017.03.060
doi: 10.1016/j.jff.2017.03.060
Yang S-H, Sharrocks AD, Whitmarsh AJ (2003) Transcriptional regulation by the MAP kinase signaling cascades. Gene 320:3–21. https://doi.org/10.1016/S0378-1119(03)00816-3
doi: 10.1016/S0378-1119(03)00816-3 pubmed: 14597384
Guo Q, Bi D, Wu M, Yu B, Hu L, Liu C, Gu L, Zhu H, Lei A, Xu X (2020) Immune activation of murine RAW264. 7 macrophages by sonicated and alkalized paramylon from Euglena gracilis. BMC Microbiol 20:1–10. https://doi.org/10.1186/s12866-020-01782-y
doi: 10.1186/s12866-020-01782-y
Patin EC, Thompson A, Orr SJ (2019) Pattern recognition receptors in fungal immunity. Semin Cell Dev Biol 89:24–33. https://doi.org/10.1016/j.semcdb.2018.03.003
doi: 10.1016/j.semcdb.2018.03.003 pubmed: 29522806 pmcid: 6461132
Tang Z, Huang G (2022) Extraction, structure, and activity of polysaccharide from Radix astragali. Biomed Pharmacother 150:113015. https://doi.org/10.1016/j.biopha.2022.113015
doi: 10.1016/j.biopha.2022.113015 pubmed: 35468585
Mueller A, Raptis J, Rice PJ, Kalbfleisch JH, Stout RD, Ensley HE, Browder W, Williams DL (2000) The influence of glucan polymer structure and solution conformation on binding to (1→ 3)-β-D-glucan receptors in a human monocyte-like cell line. Glycobiology 10:339–346. https://doi.org/10.1093/glycob/10.4.339
doi: 10.1093/glycob/10.4.339 pubmed: 10764821
Kaczmarska A, Pieczywek PM, Cybulska J, Zdunek A (2022) Structure and functionality of Rhamnogalacturonan I in the cell wall and in solution: a review. Carbohydr Polym 278:118909. https://doi.org/10.1016/j.carbpol.2021.118909
doi: 10.1016/j.carbpol.2021.118909 pubmed: 34973730
Ghosh K, Takahashi D, Kotake T (2023) Plant type II arabinogalactan: structural features and modification to increase functionality. Carbohydr Res. https://doi.org/10.1016/j.carres.2023.108828
doi: 10.1016/j.carres.2023.108828 pubmed: 37182471
Gotoh S, Naka T, Kitaguchi K, Yabe T (2021) Arabinogalactan in the side chain of pectin from persimmon is involved in the interaction with small intestinal epithelial cells. Biosci Biotechnol Biochem 85:1729–1736. https://doi.org/10.1093/bbb/zbab068
doi: 10.1093/bbb/zbab068 pubmed: 33877300
Guo R, Chen M, Ding Y, Yang P, Wang M, Zhang H, He Y, Ma H (2022) Polysaccharides as potential anti-tumor biomacromolecules—a review. Front Nutr 9:1–12. https://doi.org/10.3389/fnut.2022.838179
doi: 10.3389/fnut.2022.838179

Auteurs

Seung-U Son (SU)

Department of Food Science and Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea.
Transdisciplinary Major in Learning Health System, Department of Integrated Biomedical and Life Science, Korea University, Seoul, 02841, Republic of Korea.

Hee Won Lee (HW)

Department of Food Science and Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea.

Ju-Hyeon Park (JH)

Department of Food Science and Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea.

Kwang-Soon Shin (KS)

Department of Food Science and Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea. ksshin@kyonggi.ac.kr.

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