Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions
Abstract
:1. Introduction
2. Current Research Status of NAG Polysaccharides: An Overview
3. Extraction, Purification, and Characterization of NAG Polysaccharides
4. Immunomodulatory Properties of NAG Polysaccharide Extracts
5. Mechanisms of Immunomodulation by NAG Polysaccharides
5.1. Overview
5.2. Receptors of the Innate Immune System that Potentially Bind to NAG Polysaccharides
5.2.1. TLRs
5.2.2. C-type Lectin Receptors
5.2.3. CR3, SRs, and NOD-2
5.3. NAG Polysaccharide Classes and Their Immunomodulatory Mechanism
6. Recent Innovations and Future Directions
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name | Structural Features of Isolated Polysaccharides | Molecular Weight (kDa) | Ref |
---|---|---|---|
AGC1 | Composed of Gal (60.093%), Ara (19.165%), Xyl (11.363%), Glc (6.298%), Rha (1.548%), and Man (0.79%); contains type II arabinogalactans | 5.2 | [14] |
AGC3 | Composed of Ara (7.8%), Rha (8.1%), Glc 92%), Gal (74.3%), GalA (6.8%), GluA (1%), and trace amounts of Man and Xyl; contains RG-I polysaccharide | 4.81 and 32.14 | [37] |
GSP | Composed of Rha, Ara, Gal, Glc, and GalA in a molar ratio of 1:4:8:8:50; pectic polysaccharide with a major homogalacturonan domain and a minor RG-I component | 85.4 | [33] |
PPQN | Composed of Glc and Gal in a molar ratio of 1:1.15 | 3.1 | [48] |
PPQA2 | Composed of Ara, Rha, Man, Gal, Glc, GalA, and GluA in a molar ratio of 8:4:2.9:7.2:12.5:26.6:38.8 | 23 | [38] |
PPQA4 | Composed of Ara, Rha, Man, Gal, Glc, and GluA in a molar ratio of 19.7:5.1:8.1:23.9:41.3:2 | 120 | [38] |
PPQA5 | Composed of Ara, Rha, Man, Gal, Glc, GalA, and GluA in a molar ratio of 8.5:3.2:5.3:10.8:32.4:15.5:24.4 | 5.3 | [38] |
AEP-1 | Composed of Glc, Gal, and GalA in a molar ratio of 4.67:0.97:3.92 | N/A | [31] |
AEP-2 | Composed of Ara, Man, Gal, Glc, and GalA in a relative molar ratio of 1.03:0.76:1.68:3.02:3.65 | N/A | [31] |
WPS-1 | Composed of Ara, Rha, Man, Gal, and Glc in a ratio of 21.2:2.3:2.6:18.7:55.2 | 1540 | [35] |
WPS-2 | Composed of Ara, Rha, Man, Gal, and Glc in a ratio of 27.9:1.7:2.9:20.7:46.8 | 14.1 | [35] |
SPS-1 | Composed of Ara, Xyl, Man, Gal, Glc, Gala, and GlcA in a ratio of 22.3:6.9:9.2:28.6:15.9:13.6:3.5 | 362 | [35] |
SPS-2 | Composed of Ara, Xyl, Man, Gal, Glc, Gala, and GlcA in a ratio of 14.2:5.3:7.9:22.5:25.3:16.9:7.9 | 9700 | [35] |
SPS-3 | Composed of Ara, Rha, Xyl, Man, Gal, Glc, GalA, and GlcA in a ratio of 19.2:2.1:9.6:12:15.2:11.5:26.3:4.1 | 512 | [35] |
PPQ | Composed of Glc and Gal in a molar ratio of 2.1:1 | 54 | [47] |
Quinquefolan A | Composed of Man and Glc in a ratio of 1.0:2.3 and 10.8% uronic acid | >2000 | [46] |
Quinquefolan B | Composed of Man and Glc in a ratio of 1.0:5.5 and 11.7% uronic acid | >2000 | [46] |
Quinquefolan C | Composed of Xyl and 7.1% uronic acid | >2000 | [46] |
Name of Polysaccharide | Immunomodulatory Findings | Model | Endotoxin Test | Ref |
---|---|---|---|---|
N/A (Crude polysaccharide) | Stimulated TNF-α | Alveolar macrophages isolated from male Wistar rats | Yes | [29] |
N/A (Polysaccharide Nanoparticles) | Stimulated NO, TNF-α, IL-6, and IL-1β | RAW 264.7 murine macrophage cells | Not reported | [52] |
N/A (Fluorescein-5-thiosemicarbazide labelled polysaccharide nanoparticles | Uptake of nanoparticles by macrophages, stimulated NO, TNF-α, IL-6, and IL-1β | RAW 264.7 murine macrophage cells | Not reported | [53] |
N/A Gelatin-encapsulated Polysaccharide Nanoparticles | Stimulated NO, TNF-α, IL-6, and IL-1B (in vitro); stimulated NO and TNF-α in blood serum (in vivo) | RAW 264.7 murine macrophage cells (in vitro); swiss albino mice (in vivo) | Not reported | [54] |
N/A (crude and partially purified polysaccharide fractions of different molecular weights) | Stimulated NO and TNF-α (in vitro, ex vivo, and in vivo); suppressed NO and TNF-α in LPS-stimulated cells (in vitro, ex vivo, and in vivo) | RAW 264.7 murine macrophage cells (in vitro); alveolar macrophages isolated from adult male rats (ex vivo); adult male rats (in vivo) | Not reported | [12] |
AGC1 (Purified neutral polysaccharide) | Stimulated TNF-α, IL-6, MCP-1, GM-CSF, NOS2 gene expression, iNOS protein expression, NO (in vitro); stimulated splenocyte proliferation (ex vivo) | RAW 264.7 murine macrophage cells (in vitro); splenocytes isolated from CD1 mice (ex vivo) | Yes | [14] |
AGC3 (Purified acidic polysaccharide fraction) | Stimulated TNF-α, IL-6, and NO (in vitro); upregulated phospho-p65 and phospho-p38 (in vitro); stimulated splenocyte proliferation (ex vivo) | RAW 264.7 murine macrophage cells (in vitro); splenocytes isolated from CD1 mice (ex vivo) | Yes | [37] |
N/A (High molecular weight crude polysaccharides) | Stimulated IL-6, TNF-α, IFN-y, IL-1β, IL-12, IL-2; induction of Th1 immune response; induced NF-κB, MAPK and PI3K pathways | Human peripheral blood mononuclear cells, CD14+ monocytes, CD14+CD16+ monocytes | Yes | [30] |
PPQN (Purified neutral polysaccharide) | Suppressed NO, IL-1β, IL-6, and TNF-α in LPS-stimulated macrophages | RAW 264.7 murine macrophage cells | Not reported | [48] |
PPQA2, PPQA4, PPQA5 (Purified acidic polysaccharides) | Stimulated NO, TNF-α, and IL-6 | RAW 264.7 murine macrophage cells | Not reported | [38] |
N/A (Crude polysaccharide) | Stimulated IL-6, CCL5, TNF-α, and NF-KB | Mouse 3T3-L1 preadipocyte cells | Not reported | [49] |
AGP (Crude Polysaccharide) | Stimulated NO, IL-6, and IL-10 | RAW 264.7 murine macrophage cells | Not reported | [34] |
AEP (alkali-extractable crude polysaccharide), AEP-2 (Purified acidic polysaccharide) | Stimulated NO, IL-6, and TNF-α | RAW 264.7 murine macrophage cells | Not reported | [31] |
CPS (crude polysaccharide), WPS-1, WPS-2 (purified neutral polysaccharides), SPS-1, SPS-2, and SPS-3 (purified acidic polysaccharides) | Stimulated macrophage phagocytic activity and NO; augmented LPS and ConA induced splenocytic proliferation (SPS-3 > SPS-1 > CPS> WPS-1 > WPS-2 > SPS-2) | Splenocytes and peritoneal macrophages isolated from specific pathogen-free Jilin mice | Not reported | [35] |
PPQ (purified neutral polysaccharide) | Decreased tumor size; stimulated serum IL-2 and IFN-γ; reduced serum IL-10; increased thymus and spleen index in tumor-bearing mice | C57BL/6 mice (Lewis lung carcinoma model) | Not reported | [47] |
Immunomodulatory Activities of CVT-E002/COLD-FX | Model | Ref |
---|---|---|
Decreased spleen IL-2 and IFN-γ and increased IL-1β following LPS/ConA stimulation of cultured lymphocytes; lowered proportion of CD3+ (T-cells) and activated T-cells | Sprague-Dawley rats (oral administration) followed by isolation and culture of lymphocytes from spleen, mesenteric lymph nodes, and Peyer’s patches | [56] |
Reduced acute respiratory illness due to influenza or respiratory syncytial virus | Randomized, placebo controlled, double blind human clinical trial (oral administration) | [57] |
Stimulated TNF-α and IL-2; moderated granzyme-B levels | Human (oral administration) followed by isolation and culture of peripheral blood leukocytes along with influenza viruses | [58] |
Increased NK cell numbers in spleen, bone marrow, and blood | C3H/OuJ mice (oral administration) | [59] |
Reduced recurrent and mean number of colds per person and severity of symptoms | Randomized, placebo controlled, double blind human trial (oral administration) | [60] |
Increased NK cell and T-helper cell numbers and reduced IgA levels in plasma | Randomized, placebo controlled, double blind human trial (oral administration) | [61] |
Stimulated B lymphocyte proliferation; stimulated IgG in blood serum; stimulated IL-1, IL-6, TNF-α, and NO | Lymphocytes isolated from BALB/c mice; BALB/c mice (oral administration); peritoneal exudate macrophages isolated from C57BL/6 mice | [45] |
Stimulated ConA-induced IFN-γ and IL-2 | Splenocytes isolated from C57BL/6 mice | [55] |
Suppressed IFN-γ and related gene expression in dexamethasone cotreated cells | Mouse splenocytes | [62] |
Inhibited allergic airway inflammation; increased INF-γ, regulatory T-cells, and IL-10 in lungs | BALB/c mice | [63] |
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Ghosh, R.; Bryant, D.L.; Farone, A.L. Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions. Molecules 2020, 25, 5854. https://doi.org/10.3390/molecules25245854
Ghosh R, Bryant DL, Farone AL. Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions. Molecules. 2020; 25(24):5854. https://doi.org/10.3390/molecules25245854
Chicago/Turabian StyleGhosh, Rajarshi, Daniel L. Bryant, and Anthony L. Farone. 2020. "Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions" Molecules 25, no. 24: 5854. https://doi.org/10.3390/molecules25245854
APA StyleGhosh, R., Bryant, D. L., & Farone, A. L. (2020). Panax quinquefolius (North American Ginseng) Polysaccharides as Immunomodulators: Current Research Status and Future Directions. Molecules, 25(24), 5854. https://doi.org/10.3390/molecules25245854