Z. Yin et al.

/ Food Science and Human Wellness 10 (2021) 393-400 393

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journal homepage: http://www.keaipublishing.com/en/journals/food-science-and-human-wellness

Immunomodulatory effects of polysaccharides from edible fungus: a review

Zhenhua Yina,b,c, Zhenhua Lianga,b,c, Changqin Lia,b,c, Jinmei Wanga,b,c,
Changyang Maa,b,c, Wenyi Kanga,b,c,*
a
National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, Henan 475004, China
b
Joint International Research Laboratory of Food & Medicine Resource Function, Kaifeng, Henan 475004, China
c
Functional Food Engineering Technology Research Center, Kaifeng, Henan 475004, China

ARTICLE INFO ABSTRACT

Article history: The polysaccharides from edible fungus showed many kinds of biological activities, including anti-tumor,
Received 3 December 2020
immunomodulatory, DQWLLQÀDPPDWRU\ DQWLGLDEHWHV LPSURYLQJ IXQFWLRQDO FRQVWLSDWLRQ DFWLYLWLHV ,Q
Received in revised form 21 December 2020
Accepted 24 December 2020 particular, the immunomodulatory effects have been paid more and more attention by scholars, but there
Available online 17 May 2021
ZDV QR V\VWHPDWLF LQWURGXFWLRQ RI WKHLU LPPXQRPRGXODWRU\ PHFKDQLVP 6R WKLV UHYLHZ LQWURGXFHG WKH
Keywords: immunomodulatory effects and mechanism of edible fungus polysaccharides in recent years, and then the
Edible fungus UHODWLRQVKLSVEHWZHHQVWUXFWXUHDQGLPPXQRPRGXODWRU\HIIHFWZHUHDOVRGLVFXVVHG
Polysaccharides
© 2021 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. on behalf of KeAi
Immunomodulatory effect
Mechanisms-immunomodulatory relationship Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction
Immune response, as an important physiological process, can
identify and destroy foreign harmful substances or organisms to
RTQVGEV FKUGCUG KP YJKEJ OCETQRJCIGU RNC[ UKIPKſECPV TQNGU KP
phagocytosis, cytotoxicity and intracellular killing activities [1].
Once activated, macrophages can resist pathogens either directly
through phagocytosis or indirectly by producing related factor,
including nitric oxide (NO), interleukins (IL), tumor necrosis
factor-Į (TNF-Į) and reactive oxygen species (ROS). The
mechanism of action is related to mitogen-activated protein
kinase (MAPK) and nuclear factor kappa B (NF-ț%) via pattern
recognition receptors (PRRs) [2]. In addition, it can play the role
of immune regulation through oxidative stress and lymphocytes.
At present, the edible fungus have attracted increasing attention
#
These authors contributed equally to this work.
* Corresponding author.
E-mail address: kangweny@hotmail.com (W.Y. Kang)
Peer review under responsibility of KeAi Communications Co., Ltd
due to their nutritional and medicinal values and their bioactive
components, especially their immunomodulatory activity.
Edible fungus, also known as mushrooms, are found around
15 000 species all over the world, of which 650 species have been
UHSRUWHGWRKDYHPHGLFLQDOYDOXH>@ Mushrooms have attracted more
and more attention because of nutritional and medicinal values and
ULFKELRDFWLYHFRPSRQHQWV>@0XVKURRPVFRQWDLQHGPDQ\ELRDFWLYH
components, including polysaccharides, active proteins, glycosides,
alkaloids, volatile oils, phenols, ketones and organic acids, which
VKRZHGLPPXQHUHJXODWLRQDQWLWXPRUDQWLK\SRJO\FHPLDDFWLYLWLHV>@
Polysaccharides, as a major bioactive substance of mushroom,
VKRZHG DQWLWXPRU DQWLLQÀDPPDWRU\ LPPXQRPRGXODWRU\ anti-
diabetes, improving functional constipation activities [6-10], the
LPPXQRPRGXODWRU\DFWLYLWLHVKDYHEHHQDWWUDFWLQJLQFUHDVLQJDWWHQWLRQ
,QWKLVUHYLHZWKHPHFKDQLVPVRILPPXQRPRGXODWRU\HIIHFWVRI
SRO\VDFFKDULGHVIURPHGLEOHIXQJXVZHUHVXPPDUL]HG,QDGGLWLRQ
the relationships between structure and immunomodulatory activities
ZHUHDOVRGLVFXVVHG

http://doi.org/10.1016/j.fshw.2021.04.001
2213-4530/© 2021 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
394 Z. Yin et al. / Food Science and Human Wellness 10 (2021) 393-400

2. Immunomodulatory mechanisms of polysaccharides  (IIHFWVRISRO\VDFFKDULGHVRQ0$3.DQG1)ț%VLJQDO

from edible fungus pathways
2.1 Effects of polysaccharides on cytokines and other related The NF-țB transcription factors control the activities of genes
molecules UHODWHGWRDSRSWRVLVFHOOVHQHVFHQFHLPPXQLW\DQGLQÀDPPDWLRQ$V
GLPPHUV1)ț%LVSUHVHQWLQWKHF\WRSODVPDQGLVRODWHGE\1)ț%
Macrophages play important roles against microbial infections inhibitor protein Į ,țB-Į 8QGHU VWLPXODWLRQ ,țB-Į protein
KP VJG JQUV FGHGPUG U[UVGO YJKEJ RTQFWEG XCTKQWU KPƀCOOCVQT[ undergoes a series of phosphorylated, ubiquitinated, and degraded,
mediators, cytokines, and phagocytic activities to attack invaders, thus releasing NF-țB dimers to activate the transcription of their
such as bacteria or viruses [11]. Macrophages are in the static state WDUJHWJHQHV>@ 0$3.VLQFOXGLQJH[WUDFHOOXODUVLJQDOUHJXODWHG
under normal circumstances. But activated macrophages enhance the
production of mediators, like NO, ROS, TNF-Į, IL-1ȕ and IL-6 [12].
However, excessive activation of macrophages leads to the production
of pro-inflammatory factors, which can cause damage to living
organisms [13]. Among them, NO is an important intracellular signal
molecule that mediates a series of host defense functions of activated
macrophages. At the same time, it is also a cytotoxic agent to regulate
immune response [14]. The effects of pro-inflammatory factors
TNF-Į and IL-1ȕ on macrophages can enhance the immune response
and induce the expression of other immunomodulatory factors. IL-6
has effects on phagocytosis, antigen presentation and inflammation
regulation, and provides the third signal to T cells to regulates cellular
and humoral immunity [15]. IL-10, as a major anti-inflammatory
NLQDVHV(5.VF-XQ1WHUPLQDONLQDVHV-1.VDQGSSOD\NH\
roles in the regulating cell growth, differentiation and cell responses
WR F\WRNLQHV DQG VWUHVVHV >@ 0$3.V DOVR SOD\ UROHV IRU 1)ț%
WUDQVFULSWLRQDODFWLYDWLRQ
Edible fungus polysaccharides regulated cytokines and other
factors via NF-țB and MAPKs signal pathways. Polysaccharide
FVPB2 from F. velutipes significantly increased production of
,/ WKURXJK WKH (5./ DQG 1)ț% VLJQDOLQJ SDWKZD\V >@
3RO\VDFFKDULGH(3$IURP3OHXURWXVHU\QJLL significantly induced
WKH UHOHDVHV RI 12 ,/ 71)Į DQG ,/ E\ 1)ț%/0$3.
VLJQDOLQJSDWKZD\V>@+(3HQKDQFHGLQQDWHLPPXQHUHVSRQVHVYLD
PDFURSKDJHSKDJRF\WRVLVDQG1.FHOODFWLYLW\LQPLFHDQGSURPRWHG
adaptive immune responses via enhancing cell-mediated and humoral
LPPXQLW\XSUHJXODWHGVHFUHWRU\LPPXQRJOREXOLQ$6,J$VHFUHWLRQ
cytokine, shows immunosuppressive effect [16]. LQ WKH ODPLQD SURSULD ZKLFK ZDV UHODWHG WR 0$3. DQG SURWHLQ
Edible fungus polysaccharides play immunomodulatory roles
by regulating cytokines and other factors in RAW264.7 macrophage
cells. For example, the polysaccharides from Tremella fuciformis
stimulated the production of NO, IL-6, IL-1ȕ and TNF-Į by
increasing mRNA expressions of inducible nitric oxide synthase
(iNOS), IL-6, IL-1ȕ and TNF-Į [17]. Two polysaccharides FVPB1
NLQDVH%$.7VLJQDOLQJSDWKZD\V>@ 36*HQKDQFHGWKHOHYHOV
RI,/,)1Ȗ DQG,/YLD&D2+/&D1DQG0$3.SDWKZD\V>@
$ JOXFRJDODFWRPDQDQ ZDV REWDLQHG IURP $JDULFXV ELVSRUXV, and
FRXOGDFWLYDWH(5./0$3.DQG,ț%/NF-ț%SDWKZD\VYLDLQFUHDVing
(5./ DQG ,ț%Į phosphorylation levels, which increased the
SURGXFWLRQRI12DQGSURPRWHGWKHH[SUHVVLRQRI,/,/ȕ and
and FVP2 isolated from Flammulina velutipes increased the
concentrations of NO, TNF-Į, IL-6 or IFN-Ȗ [18,19]. Polysaccharide
PIP2-1 that extracted from Paxillus involutusUKIPKſECPVN[KPETGCUGF
the releases of TNF-Į and IL-6 [20]. Polysaccharide LEPs from
Lentinula edodes induced the secretions of NO, TNF-Į and IL-6 in
RAW264.7 cells [21]. Polysaccharide IP3a isolated from Inonotus
obliquus promoted the secretions of IL-2, IL-6, IL-12 and TNF-Į [22].
Polysaccharide GP11 that isolated from Grifola frondosa promoted
the productions of NO, TNF-Į and IL-1ȕ by stimulating mRNA
expression of iNOS and TNF-Į [23]. Polysaccharide GFP isolated
from G. frondosa fruiting body increased the levels of TNF-Į, IL-6
and IFN-Ȗ, and also increased the levels of MIP-1ȕ, MIP-1Į and
MIP-2 [24]. In addition, Se-rich polysaccharide (Se-GP11) that
isolated from Se-enriched G. frondosa increased the relatively
TNF-Į and IL-2 levels, and promoted NO production [25]. Two
polysaccharides (CEPSN-1 and CEPSN-2) isolated from Auricularia
auricula-judae promoted releases of NO, TNF-Į, IL-6 and IL-10 [26].
A ȕ-D-glucan H6PC20 obtained from Hercium erinaceus
enhanced the expression of IL-6, TNF-Į and IL-1ȕ that secreted
by THP-1 macrophages [27]. In addition, polysaccharide
HEP-S increased the secretion of IL-2, IL-4 and IFN-Ȗ in spleen
lymphocytes [28]. Ganoderma lucidum polysaccharides GL-PS
increased the concentration of serum IL-2, TNF-Į and IFN-Ȗ in rats
[29]. Table 1 summarizes the effects of polysaccharides on cytokines
and other related molecules.
TNF-Į L126 DQG F\FORR[\JHQDVH &2; >@ Cordyceps
militaris SRO\VDFFKDULGH &03,,, FRXOG LQFUHDVH macrophage
phagocytosis and secretion of factors via MAPKs/NF-țB signaling
pathways [38]. Table 2 summarizes the effects of polysaccharides on
MAPK and NF-țB signal pathways.
2.3 Effects of polysaccharides on oxidative stress
2[LGDWLYH VWUHVV LV UHODWHG WR DEQRUPDO LPPXQH UHVSRQVH >@
%DVHG RQ WKH R[LGDWLRQLQIODPPDWLRQ WKHRU\ EHFDXVH R[LGDQWV
DUH LQIODPPDWRU\ IDFWRUV H[FHVVLYH SURGXFWLRQ RI R[LGDQWV FDXVH
LQÀDPPDWLRQUHVSRQVH2[LGDWLYHVWUHVVOHDGWRGHFUHDVHRILPPXQH
FHOOVIXQFWLRQ>@
Some polysaccharides enhanced immune function by
protecting the body from oxidative stress. In the spleen and thymus
immunosuppressed mice, G. atrum polysaccharide PSG-1 improved
immune dysfunction by regulating the production of ROS and
apoptosis [41]. C. militaris polysaccharides (CMP) improved the
immune function in mice, which was related to protection against
oxidative stress [42].
The nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling
pathway participated in regulating inflammation and immune
response. Nrf2 regulated antioxidant and eliminated excess ROS [43].
Wang et al. [44] proved that Sarcodon imbricatus polysaccharide
SIPS acted on Nrf2-mediated oxidative stress to effectively reverse
Table 1
The effects of polysaccharides on cytokines and other related molecules.
Source Name Molecular weight (Da) Monosaccharide composition Experimental model Immunomodulatory activity Mechanism Reference
4 RAW 264.7 cell,
F. velutipes PVPB1 2.04 × 10 Gal, Man, Fuc and Glu (1.8:1.2:1:15.4) Increase the levels of IL-1ȕ, IL-6 and TNF-Į - [18]
and T cell
4
F. velutipes FVP2 î *DO%*OX%DQG0DQ%) 5$:FHOO (QKDQFHWKHH[SUHVVLRQRI1271)ĮDQG,/ - >@
I. obliquus ,3D  5KD$UD*OXDQG*DO Mice ,QFUHDVHWKHOHYHOVRI,/,/,/DQG71)Į - [22]
3 Stimulate mRNA expression to produce NO, Through the TLR4
G. frondosa *3 î 0DQ*OXDQG*DO 5$:FHOO [23]
TNF-Į and IL-1ȕ signaling pathway
G. Frondosa fruiting Increase cytokines TNF-Į, IL-6, IFN-¤, MIP-1ȕ, MIP-1Į and

Z. Yin et al. / Food Science and Human Wellness 10 (2021) 393-400

GFP 1.55 × 105 Rha, Xyl, Man, Glu (1.00:1.04:1.11:6.21) RAW264.7 cell - [24]
body MIP-2 levels
Mice. RAW 264.7 Increase the relatively thymus weight, spleen weight and TNF-¢
Se-G. frondosa Se-GP11 3.3 × 104 Man, Glu and Gal (1:4.91:2.41) - [25]
cell and IL-2 levels, promote NO production
3
Submerged culture of CEPSN-1 4.6 × 10 Glu, Man, Gal and GluA
RAW 264.7 cell Promote the release of NO, TNF-Į, IL-6 and IL-10 - [26]
A. auricula-judae CEPSN-2 6.7 × 103 Glu, Man, Gal, Ara, Fuc, GluA and GalA
Human monocytic Induce lymphocytes proliferation and enhance the expression of
Hericium erinaceus H6PC20 2.39 × 106 ȕ-D-glucan - [27]
cell line THP-1 IL-6, TNF-Į and IL-1ȕ
Spleen lymphocyte In spleen lymphocytes, increase the IL-2, IL-4 and IFN-Ȗ
Rha, Fuc, Man, Glu and Gal and murine secretion; In RAW 264.7 cells, promote the secretion of NO and TLR2 membrane
H. erinaceus HEP-S 1.83 h 104 [28]
(1.47:0.93:1.36:8.68:4.08) macrophage RAW IL-6, and TNF-Į by activating the corresponding mRNA and receptor
264.7 cells protein expression

Table 2
The effects of polysaccharides on MAPK and NF-țB signal pathways.
Molecular Monosaccharide
6RXUFH Name ([SHULPHQWDOPRGHO ,PPXQRPRGXODWRU\DFWLYLW\ Mechanism Reference
weight (Da) composition
*DO0DQ)XFDQG*OX ,QFUHDVH,J0DQG,J*OHYHOV -
F. velutipes PVPB2 î4 Mouse B lymphocytes [33]
) Upregulate effect on IL-10 production Through the ERK1/2 and NF-ț% signaling pathways
Man, Glu and Gal Activate signal protein of p38, ERK, JNK in MAPKs and
3HU\QJLL EPA-1 9.97 × 104 RAW 264.7 cell Induce secretion of NO, IL-1, TNF-Į, and IL-6 [34]
(2.2:1.0:3.2) translocation of nuclear NF-țǺ
Ganoderma Man, Gal and Glu Promote proliferation and increase the
PSG-1 1.013 × 106 T lymphocytes Via Ca2+/CaN and MAPK pathway. [36]
atrum (1:1.28:4.91) production of IL-2, IFN-Ȗ and IL-12
,QFUHDVH12SURGXFWLRQE\LQFUHDVLQJWKHH[SUHVVLRQRIL126LQFUHDVHWKH
$JDULFXV $FWLYDWHG(5./0$3.DQG,ț%/1)ț%SDWKZD\VYLD
7- î5 *OXFRJDODFWRPDQDQ 5$:FHOO H[SUHVVLRQRI&2;DQGWKHP51$OHYHOVRI [37]
bisporus LQFUHDVLQJSKRVSKRU\ODWLRQOHYHOVRI(5./DQG,ț%Į
,/ȕ,/71)ĮDQG&2;
*DO*OXDQG0DQ Promote macrophage phagocytosis and secretion of 0DFURSKDJHDFWLYDWHGLQYROYHG0$3.VDQG
C. militaris &03ċ î7 5$:FHOO >@
 1271)ĮDQG,/ QXFOHDU1)ț%VLJQDOLQJSDWKZD\V

395
396 Z. Yin et al. / Food Science and Human Wellness 10 (2021) 393-400

cyclophosphamide (CTX)-induced immunosuppression. The relevant further to regulate cytokines and other factors. For example, HEP-S
mechanism is shown in Fig. 1. activated the corresponding mRNA and protein expression to release
NO and IL-6, and TNF-Į, which involved TLR2 membrane receptor
CTX [38]. Amillariella mellea polysaccharide AAMP-A70 increased
Polysaccharides
the secretions of NO, ROS, TNF-Į, IL-6 and IL-1ȕ by activating
macrophages via NF-țB/MAPK signaling pathways and TLR2
NO, IL-1β, IL-6, receptor [48]. CMPB90-1 activated TLR2, MAPK/NF-țB pathways,
TNF-α, ROS, COX-2 which promoted lymphocyte to secrete NO, TNF-Į and IL-2, up-
Suppress immune regulated T-cell subsets, enhanced phagocytosis of macrophages
system function
and induced M1 [49]. GP11 acted on TLR-4 pathway to stimulate
the releases and mRNA expression of NOCPFKPƀCOOCVQT[HCEVQTU
[23]. $JDULFXVEUDVLOLHQVLV polysaccharides stimulated TLR4/myeloid
Spleen differentiation 88 (MyD88) and TLR4/TIR-domain-containing
Thymus
adapter-inducing interferon-ȕ (TRIF) pathways to induce the
ROS UGETGVKQPUQHKPƀCOOCVQT[HCEVQTUCPF%1:=?2QN[UCEEJCTKFG
DIP from Dictyophora indusiata induced NO, IL-1ȕ, IL-6 and TNF-Į
P production by increasing mRNA expression levels of related factors
Nrf2
via TLR4/NF-țB signaling pathways [51]. G. frondosa polysaccharide
Fig. 1 The relevant mechanism of polysaccharides from edible fungus on (GFPS) activated macrophages via TLR4-MyD88-inhibitor kappa
oxidative stress. B kinase ȕ (IKKȕ)-NF-țB p65 signaling pathways to induce the
release of NO, and increase the levels of IL-10, IL-1ȕ, granulocyte-
colony stimulating factor (G-CSF), monocyte chemotactic protein
2.4 Effects of polysaccharides on PRRs
(MCP)-3 and interferon inducible protein-10 (IP-10) in RAW264.7
In most cases, macromolecular polysaccharides cannot enter cells cells [52]. Polysaccharide CRP isolated from Collybia radicata
directly because of their large molecular mass, but polysaccharides activated murine macrophages through TLR4, and induced release
can recognize PRRs to enter cells [45]. PRRs, including ȕ-glucan of NO, iNOS and inflammatory factors [53]. Glucogalactan TLH-3
receptor, dectin-1 receptor, mannose receptor (MR), complement from Tricholoma lobayense increased secretions of NO, IL-6 and
receptor type 3 (CR-3) and toll-like receptors (TLRs), activate TNF-Į by activating the IțB-Į-NF-țB pathways via TLR-4 [54,55].
macrophages by binding of polysaccharides [46]. TLRs are one kind Polysaccharide F2 isolated from Schizophyllum commune activated
of important PRRs in macrophages. Among them, TLR2 and TLR4 NF-țB/MAPK pathways via acting on CR-3 and TLR-4, furthermore,
are involved in the recognition of a wide range of pathogen associated a large amount of NO and other cytokines were produced by
molecular patterns [47]. increasing the expression levels of related mRNA [56]. The relevant
Edible fungus polysaccharides could activate macrophages via mechanism is shown in Fig. 2. Table 3 reports a summary of effects
PRRs that activating NF-țB, MAPKs and other signal pathways, and of polysaccharides on PRRs.

Poplysaccharides
Poplysaccharides

TLR4
TLR2

MyD88
P TRIF
P

MAPK P
NF-κB IκB-α
JNPs
P
ERKs p38
P

NF-κB IκB-α

NO, IL-1β, IL-6,

TNF-α, ROS, COX-2
Degradation
Transcription

Fig. 2 The NF-țB and MAPK signal pathways via TLR-2 and TLR-4.
 Z. Yin et al. / Food Science and Human Wellness 10 (2021) 393-400 397
Table 3
The effects of polysaccharides on PRRs.
Molecular Monosaccharide
Source Name ([SHULPHQWDOPRGHO ,PPXQRPRGXODWRU\DFWLYLW\ Mechanism Reference
weight (Da) composition
$FWLYDWHPDFURSKDJH
,QFUHDVHPDFURSKDJHSKDJRF\WRVLV
3 *OX%) and GHSHQGHQWRQ1)ț%/0$3.
A. mellea $$03$ î 5$:FHOO DQGVHFUHWLRQRI12526,/ >@
*DO%), trace Man VLJQDOLQJSDWKZD\VYLDWKH7/5
71)ĮDQG,/ȕ
receptor
Promote lymphocyte to secrete -
6SOHQLFO\PSKRF\WH
1271)ĮDQG,/XS
3 *DO*OXDQG <$&O\PSKRPD
C. militaris &03% î regulated T-cell subsets, enhance >@
0DQ cell, natural killer cell, $FWLYDWHG7/5
phagocytosis of macrophages
5$:FHOO 0$3.DQG1)ț%SDWKZD\V
and induced M1
,QGXFHG12,/ȕ,/DQG
71)ĮSURGXFWLRQE\LQFUHDVLQJ 9LD7/5/1)ț%
D. indusiata ',3 î5 ȕ-D-glucan 5$:FHOO [51]
P51$H[SUHVVLRQOHYHOVRI signalling pathway
related factors
5LE*OXDQG;\O Induce cells to release NO,
Activate murine
C. radicata &53  and a small amount of Man, Rha, RAW264.7 cell iNOS, IFN-Ȗ, [53]
macrophages via TLR4
*DODQG*DO$ IL-6, IL-1ȕ and IL-10

Increased secretion of NO, IL-6 NF-țB signaling

T. lobayense TLH-3 4.53 × 103 - RAW 264.7 cell [54-55]
and TNF-Į pathway via TLR-4

(1ĺ3)-linked-mannopyranosyl and Produce NO and other cytokines Through NF-țB and MAPK
5.337 × 105, 9.35
S. commune F2 (1ĺ2,3)-linked- RAW264.7 cell were produced by up-regulating the pathways by activating CR-3 and [56]
× 104, 7.98 × 104
mannopyranosyl residues expression levels of related mRNA TLR-4 receptors

 (IIHFWVRISRO\VDFFKDULGHVRQLQWHVWLQDOPLFURÀRUD
,QWHVWLQDO PLFURIORUD KDV LPSRUWDQW HIIHFW RQ LPPXQH V\VWHP
GHYHORSPHQW DQG LPPXQH IXQFWLRQ UHJXODWLRQ >@ 'LVRUGHU RI
LQWHVWLQDO PLFURIORUD DIIHFWV KXPDQ KHDOWK >@ ;X HW DO >@
GHPRQVWUDWHGWKDWSRO\VDFFKDULGH/ derived from L. edodes altered
LQWHVWLQDOPLFURELRWDVSDWLDOVWUXFWXUHLQPLFH3RO\VDFFKDULGH3(3
isolated from 3HU\QJLL could alter fecal microbiota composition and
UHJXODWHWKHLPPXQHUHVSRQVHRIWKHKRVW>@)93DOVRLPSDFWHG
RQJXWPLFURELRWDLQUDWV>@
2.6 Effects of polysaccharides on immune system
Edible fungus polysaccharides had the effect on immune system.
For example, Yu et al. [61] found that PSG-1 activated spleen
lymphocytes via the Ca2+/CaN/nuclear factor of activated T cells
(NFAT)/IL-2 and protein kinase C (PKC)/NFAT/IL-2 signaling
pathways. Lentinan, tremellan, and pachymaran polysaccharides
increased index of thymus in CXT-induced immunosuppression
mice, increased the levels of serum antibody immunoglobulin (Ig) G
and IgM [62]. GFP-A from G. frondosa increased thymus index and
spleen index, and lactate dehydrogenase (LDH) and acid phosphatase
(ACP) levels in spleen, the mRNA levels of inflammatory factors
in spleen. In addition, it also increased CD 4+ and CD 8+ splenic
T lymphocytes expression [63]. For CTX-treated mice, GFP-22
enhanced immune organ index, splenocyte proliferation and cytokines
levels in splenocytes, further improved immunosuppression [64].
%/2$UKIPKſECPVN[GPJCPEGFVJGRTQNKHGTCVKQPQHN[ORJQE[VGU
increased the activation potential of T cell and B cell, and
enhanced humoral and cellular immunity, also enhanced the killing
activity of splenocytes NK cells. In the presence of CMPB90-1,
the percentage of CD4+ and the ratio of CD4+/CD8+ T lymphocytes
increased [49]. GLP-1 isolated from G. lucidum protected spleen
and thymus and promoted hematopoiesis and improving the level
of IgA in serum [65]. Table 4 reports a summary of effects of
polysaccharides on immune system.
3. Structure-immunomodulatory activity relationship
The immunomodulatory activities of polysaccharides are

Table 4
A summary of effects of polysaccharides on immune system.
Molecular Monosaccharide Experimental
Source Name Immunomodulatory activity Mechanism Reference
weight (Da) composition model
9LD&D2+/&D1/1)$7/,/DQG3.&/
0DQ*DODQG*OX ,QGXFHDFWLYDWLRQRI
G. atrum 36* î6 5$:FHOOV 1)$7/,/VLJQDOLQJSDWKZD\V [61]
 spleen lymphocytes
cooperatively regulated
,QFUHDVHLPPXQHRUJDQLQGH[VSOHQRF\WH
0DQ*OXDQG*DO
G. frondosa *)3 î4 Balb/c mice proliferation and cytokines levels in - [64]

splenocytes, improve immunosuppression
*OX%0DQ%), Protect spleen and thymus and promote
*/3 î5
*DO%DQG)XF%) KHPDWRSRLHVLVDQGLPSURYH,J$OHYHOVLQVHUXP
G. lucidum .XQPLQJPLFH - [65]
*OX%0DQ%)
*/3 î4 7KHHIIHFWVZHUHORZHUWKDQWKDWRI*/3
DQG*DO%)
398 Z. Yin et al. / Food Science and Human Wellness 10 (2021) 393-400
MAPKs signal pathway
NF-κB signal pathway
Poplysaccharides
Nrf2-mediated oxidative stress
Intestinal microflora
Immune system
Fig. 3 The immunomodulatory of polysaccharides from edible fungus.
affected by their molecular weight, monosaccharide composition,
Į/ȕ-configuration, conformation, glycosidic linkage, branching
degree, length of side chains, and so on.
The chain conformation of polysaccharides affected the
immunomodulatory activity. Polysaccharides have different chain
conformations in solution, including random crimping, double or
triple strands, rod-like and spherical [66]. Among them, the activity
of polysaccharides is higher at the triple helix state [67,68]. In addition,
Li et al. [65] found that polysaccharide GLP-1 was a D-galactoglucan
CPFJCFƀGZKDNGTCPFQONKPGCTEQPHQTOCVKQP*QOQIGPGQWUȕ-D-glucan
GLP-2 was a spherical conformation, but GLP-1 had better protective
effect on the spleen and thymus and promoted hematopoiesis and
improved the level of IgA in serum.
At the same time, conformation changed with the variation of
molecular weight. Generally, molecular weight has been recognized
as a critical parameter of immunomodulatory activity [69,70]. As
can be seen in Table 2, polysaccharides with immunomodulatory
activity were isolated from edible fungus, the molecular weight of
most polysaccharides is more than 104 Da, and some are even higher
than 107 Da, but there are also some polysaccharides whose molecular
weights are less than 104 Da.
In addition, polysaccharides and polysaccharide-protein
complexes showed different immunomodulatory activities. For
example, Liu et al. [71,72] found that a polysaccharide-protein
NO, ROS, COX-2
Pro-inflammatior Immune regulation
Maintain intestinal microflora
Serum antibody
could activate the corresponding signal pathway by recognizing the
corresponding membrane receptors, so as to stimulate the releases of
related factors, which played a role in immune regulation. In addition,
the polysaccharides could also regulate immune activity by acting on
intestinal microorganisms and immune organs (Fig. 3).
Based on the analysis of structure-activity relationship, structure
of polysaccharides affected immunomodulatory activities. At
present, because of the complexity of structure and components of
polysaccharides, the complete structure was difficult to determine.
Therefore, the structure-activity relationship could not be completely
determined.
Most of the reported on the studies of immunomodulatory
activities have been performed in vivo or in vitro, which could
not fully reflect the actual role of polysaccharides in human body.
Therefore, the mechanism and application of polysaccharides in body
still needs to be further studied.
Declaration of competing interest
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Acknowledgement
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