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Role ofNatural Polysaccharides intheManagement ofLifestyle Diseases
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The water-soluble polysaccharides AWSP isolated from
almond (Prunus amygdalus var. amara) and PWSP from pis-
tachio (Pistacia vera) juice processing by-products, both
have shown ACE-inhibitory activity in concentrationdependent way [60]. Polysaccharide fraction of Lycium bar-
barum L. (Gouqi) efciently lowers nitric oxide or
endothelium-derived relaxation factor (EDRF) or both SBP
and DBP in 2K1C-renovascular hypertensive rats.
Dendrobium ofcinale (Tiepishihu) has recently shown lowering of BP in hypertensive rats. Through ACE-inhibitory
activity, a homogeneous polysaccharide known as CGP, isolated from the enzyme-assisted extraction of Crassostrea
gigas, has demonstrated similar hypotensive effects to captopril in both SBP and DBP [61].
4.4 Cardiovascular Diseases
In addition to hypertension, coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart
disease, congenital heart disease, deep vein thrombosis, and
pulmonary embolism, a group of heart and blood vessel disorders known as CVDs are the leading cause of death worldwide. Hyperglycemia and hyperlipidemia pose the highest
risk to cardiovascular health. Hyperglycemia indirectly
weakens heart muscles and perfusion. Hyperlipidemia
directly deposits lipids in blood vessels, causing serious
issues like atherosclerosis, coronary thrombosis, and deep
vein thrombosis. All the lifestyle factors that cause hyperglycemia and hyperlipidemia, like smoking, a sedentary lifestyle, alcoholism, lack of physical exercise, less sleep, and
huge stress eventually become reasons for CVDs [62].
4.4.1 Polysaccharides Acting Against CVDs
All polysaccharides that act against hyperlipidemia and
hyperglycemia usually have cardioprotective action. Antihypertensive polysaccharides have already been discussed.
So, this portion will try to discuss basically on the polysaccharides acting against other CVDs.
4.4.1.1 Auricularia Polysaccharides
Polysaccharides from Auricularia auricula have been found
to possess antioxidant activity and anticoagulant activity. In
mice, polysaccharide administration dramatically increased
myocardial SOD and GSH-Px levels and decreased myocardial MDA levels, demonstrating antioxidant activity [63].
4.4.1.2 Astragalus Polysaccharide
Astragalus membranaceus, commonly known as Huang Qi
in China, produces astragalus polysaccharide (APS), which
is derived from the dried roots, has shown dose-dependent
anti-hypertrophic effect in isoproterenol (ISO)-induced car-
diomyocyte hypertrophy. The production of fetal genes such
as atrial natriuretic peptide (ANP) and B-type natriuretic
peptide (BNP), which were downregulated by APS, is
increased in cardiomyocytes during hypertrophy [64].
4.4.1.3 Red Microalga Polysaccharides
Red microalga polysaccharides (PSs) are produced from
Porphyridium sp. (Rhodophyta), algal capsule. The PS positively regulates NO formation and endothelium-dependent vessel relaxation in different models and/or inactivates ROS [65].
4.4.1.4 Dendrobium Polysaccharides
Dendrobium ofcinale polysaccharide stimulated SOD,
meis1 expression, and downregulated cardiomyocyte apoptosis, thereby improved myocardial ischemia in mice with
ligated coronary arteries. Effects of Dendrobium ofcinale
onthe management of oxidative stress and apoptosis have
been observed.Additionally, H9C2 cells injured by hydrogen
peroxide (H2O2) have demonstrated polysaccharides on cardiomyocytes [57].
4.4.1.5 Ophiopogon Polysaccharide
Through the stimulation of the SPHK/S1P/bFGF/AKT/ERK
and eNOS/NO signaling pathways, Ophiopogon japonicus
polysaccharide has demonstrated increased angiogenesis in
myocardial ischemic tissue and reduced infarct size in acute
myocardial ischemia rats. Additionally, it increased endogenous antioxidants while preserving the ionic environment in
rats with ISO-induced myocardial ischemia and sustaining
Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity [66].
4.4.1.6 Zhiqiao
Using the PI3K/Akt and ERK1/2 pathways, the acidic heteropolysaccharide CALB-3, obtained from Citrus aurantium
Linn, has been demonstrated to have cardioprotective properties against the cytotoxicity in ISO-treated rats. In vitro
study using H9c2 cells has further conrmed myocardial
protection activity of CALB-3. Mechanistically, through the
stimulation of the Akt signal pathway, CALB-3 partly prevented cardiomyocyte death [67].
4.4.1.7 Padina Tetrastromatica
The mRNA expressions of the anti-inammatory cytokines
IL-10 and NF-κB, which are produced by cardiomyocytes,
were signicantly upregulated by bioactive sulfated polysaccharides (PSPS) from the brown algae species Padina tetra-
stromatica. Hence PSPS can control inammation linked to
CVDs [68].
4.4.1.8 Opuntia Polysaccharides
Water-soluble polysaccharide opuntia polysaccharides
(ODP-Ia), puried from Opuntia dillenii has shown action
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against inammation, hyperglycemia, and hyperlipidemia.
ODP-Ia inhibits the expression of hepatic apolipoprotein B
and hepatic diglyceride acyltransferase proteins, which prevents lipid accumulation and inammatory cell inltration in
hyperlipidemic, high-calcium diet-fed rats. ODP-Ia also
modulates the enzymatic activity involved in cholesterol
metabolism. Suggesting ODP-Ia has a good preventive effect
on atherosclerosis [69].
4.4.1.9 Plantago Polysaccharides
P. asiatica L. polysaccharide (PLP), a dietary supplement
having anti-inammatory and anti-atherosclerosis effects, is
derived from Plantago asiatica L.In rats with hyperlipidemia brought on by a high-fat diet (HFD), PLP decreased
TC, TG, and non-esteried fatty acid levels while increasing
HDL-C, may be by regulating the gut microbiota and increasing SCFA levels. By lowering lipid peroxidation, boosting
the generation of NO, and inhibiting the mRNA expression
of monocyte chemotactic protein-1 and c-myc, PLP has
demonstrated inhibitory impact on the proliferation of
smooth muscle cells produced by oxidized low-density lipoprotein (Ox-LDL) [70].
4.4.1.10 Polysaccharide Krestin
In numerous studies, the protein-bound polysaccharide
Krestin (PSK), which is derived from the Coriolus versicolor
plant, has demonstrated atherosclerosis prevention by preventing the buildup of lipid peroxides and the development
of lipid-containing macrophages (foam cells) by Ox-LDL
[71].
4.4.1.11 Poria Polysaccharides
The Polyporaceae family of medicinal fungi Poria cocos
produces Poria polysaccharide (PCP), which has a number
of biological properties, including anti-inammatory, antioxidant, and immunity-boosting properties. PCP can reduce
the proliferation and migration of vascular smooth muscle
cells (VSMCs) brought on by Ox-LDL by blocking the
TLR4/NF-B p65 signaling pathway. By modulating the
PPAR-LXR-ABCA1 pathway in ApoE-knockout mice, PCP
has been discovered to enhance HDL function and boost
cholesterol reverse transport, which together contribute to its
anti-atherosclerotic action [72].
4.4.1.12 Dictyophora Polysaccharides
Two distinct polysaccharide fractions, Al-DPS and En-DPS,
were produced by alkali extraction and enzymatic hydrolysis, respectively, from Dictyophora indusiate, which is a saprophytic fungus having culinary and therapeutic signicance.
Al-DPS and En-DPS can both lower the risks of hyperlipidemia, according to invivo testing, suggesting a potential to
lessen atherosclerosis [73].
4.4.1.13 Momordica Polysaccharide
As evidenced by decreased serum levels of the biomarker
enzymes aspartate transaminase (AST), creatine kinase (CK)
isoenzyme MB (CK-MB), and lactate dehydrogenase,
Momordica charantia polysaccharide (MCP), derived from
Momordica charantia (Kugua), has shown protection from
ISO-induced myocardial infarction in vivo rodent models.
MCP also upregulated antioxidant enzymes SOD and CAT,
anti-apoptotic protein Bcl-2 expression, and lowered nuclear
factor kappa B (NF-κB) and pro-apoptotic proteins (Bax and
caspase-3) expressions [74].
4.4.1.14 Cornus Polysaccharide
In a left anterior descending coronary artery ligated MI rat
model, Cornus ofcinalis polysaccharide (COP) from
Cornus ofcinalis (Shanzhuyu) enhanced left ventricular
contractile performance and infarct size. The underlying
mechanisms of cardioprotective activity of COP may be
the upregulation of mRNA expression of peroxisome
proliferator- activated receptor-gamma coactivator (PGC)-1,
1 and nuclear respiratory factor 1 (NRF-1) and downregulation of glycogen synthase kinase-3 [75].
4.4.1.15 Tamarindus Xyloglucan
Tamarind xyloglucan (TXG), a branched heteropolysaccharide derived from seeds of Tamarindus indica Linn., has
demonstrated reduction of phosphorylation of mitogenactivated protein kinases (MAPKs) p38 and c-Jun N-terminal
kinase (JNK), which suggests its activity to reduce ROS production. These indicate a signicant cardioprotective effect
[76].
4.4.1.16 Panax Ginseng
H9c2 cells pre-treated with AP1, an acidic polysaccharide
extract of Panax ginseng exhibited the cardioprotective
effect by partially suppressing the intrinsic apoptotic pathway through mitochondrial malfunction and ROS-mediated
JNK/p38-MAPK activation [61].
4.5 Asthma andCOPD
Asthma and COPD cannot be called metabolic disorders.
Still, these 2 pulmonary disorders may be brought on by
hyperlipidemia and other causes, even though chronic
obstructive pulmonary disease (COPD) is more common
among doctors. Airway hyperresponsiveness, congestion,
excessive mucus production, and thickening and rigidity of
the airway wall are all symptoms of bronchial asthma, an
allergic inammatory disease of the airways, which can lead
to chronic progression of the condition or COPD to some
extent. Conversely, COPD is characterized by a weakly
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reversible, frequently increasing airow limitation and
linked to an aberrant inammatory response of the lung.
There are two key factors contributing to the decreased ow
seen in COPD, namely increased airow resistance by airway blockage and reduction in lung elastic recoil tension by
parenchymal deterioration [77].
The main lifestyle risk factors that directly cause asthma
are poor diet quality, a sedentary lifestyle, smoking, and obesity. According to several population-based surveys, people
with asthma engage in less physical exercise than people
without asthma [78]. Childhood asthma symptoms are signicantly correlated with a sedentary lifestyle. When physical exercises cause breathlessness, a phobia or unwillingness
may develop to avoid doing it, which makes muscles more
oxygen-seeking, which causes further breathlessness. Thus,
in a cyclic way asthma or COPD may develop. Consumption
of fast food, salt, and trans fatty acids is positively correlated
with asthma [79]. Chronic stress exposures like domestic
stress, community stressors, high crime rates, and poverty
are linked to an elevated inammatory prole, which is
linked to an increase in asthma symptoms [80]. More than
90% of people with COPD presently attribute their condition
to cigarette smoking. The development of airow restriction
in smokers with chronic bronchitis is linked to a further rise
in macrophages and T lymphocytes in the subepithelium.
Smokers suffering from COPD have more inammatory
cells present in the submucosa than in the adventitia [81].
4.5.1 Polysaccharides Acting Against COPD
andAsthma
4.5.1.1 Chitin
Fish scales, arthropod exoskeletons, fungal cell walls, and
yeast cell walls are sources of chitin, which has a variety of
uses in respiratory illnesses. Chitin functions as a powerful T
and B-cell adjuvant and resembles fungal spores in the form
of phagocytosable microparticles. Chitin microparticles
(CMP) can induce immune responses through T helper cell 1
(Th1) maturation that can be benecial for asthma. In a
study of ragweed induced allergic mouse model, oral and
intranasal administration of CMP successfully decreased
serum IgE, airway hyperresponsiveness, lung inammation,
and lung eosinophilia. They also increased the secretion of
IL-12, IFN-γ, and TNF-a while decreasing the production of
IL-4 [82]. Asthma developed in mice appears to be prevented
by microgram dosages of CMP administered intranasally
during the neonatal period [83].
4.5.1.2 Chitosan
A polysaccharide called chitosan is created when chitin is
deacetylated. Chitosan is aβ-(1, 4)-linked-D-N-acetyl glucosamine polysaccharide that is a very signicant carrier to
deliver a huge number of medicines, proteins, and biologics,
and it may be easily associated with negatively charged pharmaceuticals via electrostatic binding contact. Human airway
and alveolar region cellular linings have shown that chitosanbased nanoparticles have very low cytotoxicity. Chitosanloaded medications have been shown to have an improved
therapeutic effect because they are mucoadhesive and create
gels, so they can stay in the respiratory system for longer.
Ovalbumin-induced asthma mice models’ IL-4, TNF-α,
IL-5, and IL-13 levels and their mRNA expressions have
decreased as a result of this [84]. Rat mast cells interact with
chitosan-hyaluronic acid nanoparticles, which has a positive
impact by decreasing inammation and airtrack remodeling
[85].
4.5.1.3 Astragalus andCodonopsis Polysaccharides
Polysaccharides extracted from Astragalus membranaceus
and Codonopsis pilosula have combinatorial effects on
asthma. The benets of combining Astragalus polysaccharide (APS) with budesonide in the treatment of asthma may
be due to the modulation of dendritic cells (DCs), natural
killer cells (NK), T-regulatory cells (TREG), IL-4, and IL-10.
This new method of treating asthma may be due to these factors. In mice treated for asthma, APS plus budesonide signicantly reduced DCs compared to budesonide alone,
indicating a reversible immunological response. In COPD
mouse models, administration of Astragalus polysaccharide
and/or Codonopsis pilosula polysaccharides (CPPs) signicantly increased alveolar macrophages (AM) phagocytosis
and decreased the inammatory mediators in the lung and
circulation. In COPD mice, the effects of Astragalus polysaccharide and/or CPPs on AM phagocytosis and regional or
systemic inammation have not entirely returned to baseline.
These results suggest that CPPs and Astragalus polysaccharide may offer some protection against COPD [86].
4.5.1.4 Antrodia Polysaccharides
In Asian traditional medicine, the fungus Antrodia camphorata is frequently employed. In this study, the capacity of
dendritic cells (DCs) to suppress OVA-induced asthma and
the immunomodulatory effects of A. camphorata polysaccharides (GF2) on DCs were investigated. GF2 treatment on
LPS-activated DCs suppressed CD4+ T-cell proliferation
and T helper 2 (Th2) cell polarization with generation of
IL-10 in an allogeneic mixed lymphocyte response. GF2
injection in an allergen-inducedasthma mouse model dosedependently reduced Th2 responses, eosinophilia in the airways, and airway hyperresponsiveness [87]. Inthat model,
the production of anti-OVA IgG2a and IFN-c wasis induced,
which further triggeredTh1 responses. Ithas recently been
demonstrated that asthma isprevented by GF2 through an
inducible Th1-like TREG that also produces IL-10 and IFN-c
[88].
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4.5.1.5 Portulaca Polysaccharides
The plant Portulaca oleracea is the source of portulaca poly-
saccharides (PoPs), which demonstrates potent antiasthmatic effects by downregulating NO, inammatory
cytokines, and chemokines, decreasing oxidative stress while
enhancing antioxidant markers, and also by having potent
relaxant effects on tracheal smooth muscles via stimulation
of the adrenoceptor [89].
4.5.1.6 Ganoderma Polysaccharides
A polysaccharide fraction, PS-F2, isolated from the submerged culture uid of G. formosanum, stimulates macrophage activation by activating Toll-like receptor 4 (TLR4),
Dectin-1, and complement receptor 3.These ndings imply
that PS-F2 may be developed into a treatment for allergic
asthma [90].
4.5.1.7 Boletus Edulis Polysaccharide
The polysaccharide extract from the edible fungus Boletus
edulis (BEP) signicantly reduced airway resistance. The
ability of BEP to diminish inammatory cell inltration was
equivalent to that of conventional dexamethasone therapy.
Furthermore, after receiving Boletus edulis polysaccharide
treatment, mice had less muco substance accumulation in
their lung tissues. In youngsters with asthma, IL-4 levels
rise, while IFN-levels fall. BEP-treated mice’s lung tissues
had higher IL-4 and lower IFN-γ levels. The fraction of antiinammatory CD4+CD25+FOXP3+ TREG cells considerably increased (P 0.05) when compared to untreated
asthma animals, whereas the expression of cyclophilin A
signicantly reduced. BEP therapy outcome observed in
inducedand airway resistance is found to benearly similar
todexamethasone therapy [91].
4.6 Chronic Kidney Disease
Chronic kidney disease (CKD) refers to the clinical condition of slow gradual loss of renal function to lter blood
through them, caused by different metabolic factors, leading
to complete loss of ltration capacity. CKD causes further
consequences such as anemia, stroke, cardiovascular diseases, hypocalcemia, hypokalemia, depression, frequent
infections, etc. Renal brosis and inammation are frequent
side effects of CKD development and progression, which
can ultimately lead to end-stage renal failure. The potential
apoptotic mechanism of glomerular sclerosis in CKD may
be controlled by the pro-apoptotic factor Bax and the antiapoptotic factor Bcl-2 (B-cell lymphoma/leukemia-2).
Therefore, it appears that it is required to block the inammatory and apoptotic processes in order to treat and prevent
CKD [92]. As people age, the prevalence of CKD grows
steadily, as do other risk factors such as arterial hypertension, metabolic syndrome, diabetes, obesity, and indiscriminate use of nephrotoxic medicines [93].
In all afuent and many developing nations, diabetes,
hyperlipidemia, and hypertension are the main causes of
CKD, but glomerulonephritis and other unidentied causes
are more prevalent in Asia and sub-Saharan Africa. The burden of CKD in underdeveloped nations is exacerbated by
insufcient sanitation, a lack of access to clean water, environmental pollution, pesticide usage, painkiller misuse, and
the use of unrestricted food additives [94]. Consuming foods
high in sodium causes whole-body volume overload and
hypertension, which suggests CKD development and cardiovascular remodeling. Even when kidney function is normal,
eating too much protein may not be a good idea. A high
amino acid load leads to afferent arteriole expansion, an
increase in intraglomerular pressure, and glomerular hyperltration. In contrast, a low-protein diet reduces high glomerular ltration load and improves afferent arteriole growth.
Protein restriction has positive effects on the development of
CKD, blood pressure, and proteinuria, according to many
meta-analyses. Nevertheless, there is still no established protein consumption guideline for preventing CKD. Highcalorie diets generate overweight and obesity, and obesity
accelerates the onset and progression of CKD.In CKD, visceral fat and abdominal obesity are implicated in the regulation of many cytokines and adipokines that are linked to
insulin resistance and hyperglycemia. As a result of poor
kidney function and a steady drop-in glomerular ltration
rate brought on by hypertension, BP regulation is further
compromised. Endothelial dysfunction and modication of
the renal microvasculature are results of arterial hypertension. Kidney disease and CKD are caused by endothelial
dysfunction. Blood ow to the glomeruli declines with an
increase in RAAS activity, further deteriorating kidney function. When they block the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers reduce blood pressure and protect the kidneys and the body’s microcirculation [95].
4.6.1 Polysaccharides Used inCKD
4.6.1.1 Soybean Soluble Polysaccharides
Seeds of the Glycine sp. plant are used to make soybean soluble polysaccharide (SSPS). In CRF mice, the renal pathological damage was markedly reversed by the SSPS therapy.
High-dose SSPS was able to minimize the amount of renal
brosis, according to Masson histological examination, suggesting that it was successful in reducing kidney damage in
CRF animals.TGF-1 production has been identied as a critical mediator of renal brosis, and SSPS has drastically
decreased its mRNA expression [96].
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4.6.1.2 Pleurotus Mycelia Polysaccharides
The genus Pleurotus of the Pleurotaceae family contains
Pleurotus djamor, and its polysaccharides display a wide
range of biological activity, including anti-inammatory and
antioxidant properties. It is possible to quantify TNF-α and
IL-6in blood and tissue, two crucial inammatory factors in
the inammatory response. A prominent reduction in IL-6
and TNF-α levels and relative mRNA expression following
PMPS application to adenine-induced CRF mice suggests
that PMPS has potent anti-inammatory, anti-brosis, and
renal protective effects [97].
4.6.1.3 Ophiocordyceps Polysaccharides
The eastern Himalayan region is home to the fungus
Ophiocordyceps lanpingensis. According to studies, O. lan-
pingensis reduces oxidative stress, which helps to improve
renal dysfunction in glycerol-induced acute renal failure. By
lowering the level of ROS in CKD mouse kidneys, ophiocordyceps polysaccharides (OLP) reduced oxidative stress.
The MAPK pathway, which is implicated in renal interstitial
brosis and renal cell death, was activated by OLP, whereas
the pro-inammatory cytokines were downregulated [98].
4.6.1.4 Auricularia Polysaccharides
It has been proven that A. polytricha’s fruiting body contains
bioactive polysaccharides, which have historically been utilized as both a food and a medication. Enzymatic-hydrolysis
APS (EnAPS) and A. polytricha polysaccharide (APS) show
antioxidant activity in their protective effects. The oxidative
stress induces DNA damage, which leads to apoptosis in the
kidney. Caspase-3, the primary downstream effector of apoptosis among the caspases, may contribute to cell death via
mitochondria-dependent (Bax/Bcl-2)-induced apoptosis. On
the one hand, caspase-3 activation may control the equilibrium between the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax, whose imbalance results in apoptosis.
Renal brosis is signicantly inuenced by apoptosis. By
lowering Bax expression, blocking caspase-3 activations,
and raising Bcl-2 expression, APS and EnAPS demonstrated
potential anti-apoptotic actions. EnAPS’s low molecular
weights resulted in somewhat better effects. According to the
research now being conducted, APS and its derivatives may
be created as novel functional dietary supplements to help
prevent and reduce CKD and associated problems [99].
4.6.1.5 Cordyceps Polysaccharides
The fungus Cordyceps militaris (L.), a member of the
Ascomycetes class, utilized in traditional Chinese medicine
(TCM) in East Asia, is used as a safe source of pertinent
bioactive compounds. During the course of CRF, nitric oxide
(NO) has a protective effect for the kidney, inhibiting the
mesangial cell proliferation and decreasing the synthesis of
the mesangial matrix. The buildup of P3+ and excretion of
Ca2+ can be facilitated by the reduced glomerular ltration
rate following the development of CRF.CRF may also lower
the sources of estrogen and prevent the production of LH and
E2, which can result in an endocrine problem. According to
our ndings, treatment with C. militaris, either alone or in
combination with H. brevicor, considerably reduced the lowered concentrations of NO, Ca2+, and LH and the rise in P3+
caused by adenine. Accordingly, the progression of CRF was
either delayed or stopped, damage to the renal tubular epithelial cells was decreased, renal tubular function was restored,
functional protein synthesis was increased, the negative
nitrogen balance was addressed, and so overall renal function was improved [100].
4.6.1.6 Chitosan
Chitosan is a non-toxic polysaccharide. Industrial production of it involves deacetylating chitin from crab and prawn
shells. Chitosan interacts with several acidic compounds
thought to be uremia toxins, causing the body to expel them
and improving any residual renal function. Because blood
levels of urea and creatinine are crucial markers of renal
function, a decrease in these values denotes an improvement
in renal function. The considerable rise in serum hemoglobin
levels without the use of human erythropoietin in the therapy
group was another indication of improved renal function. A
decrease in the serum hemoglobin levels, or anemia, is frequently linked to the nephrotic syndrome. Curing this type of
anemia is challenging. Human erythropoietin is typically
used to treat anemia nephrotic syndrome patients receiving
hemodialysis, although this treatment must be long term and
comes with a number of negative effects. Therefore, people
with renal insufciency may benet from chitosan as a
dietary supplement [101].
4.6.1.7 Fucoidan
Fucoidan, sulfated polysaccharides derived from the brown
alga Laminaria japonica, includes signicant amounts of the
fucose and sulfate groups as well as negligible amounts of
the following sugars: mannose, glucuronic acid, glucose,
xylose, arabinose, and rhamnose. By controlling HO-1 and
SOD-1 gene expression through the Nrf2 signaling pathway
in HaCaT cells, fucoidan reduced oxidative stress. Fucoidan
can enhance SOD and GSH-Px stimulation in the kidney and
hippocampus and lower the level of MDA, according to the
results of the current study. Additionally, the ndings
revealed that fucoidan protected tissue from adenine-induced
harm by downregulating GSK-3 and activating the antioxidant responses mediated by the Nrf2-HO-1 signaling pathway. According to another investigation, downregulation of
the MAPK and NF-κB signaling pathways and the subsequent decrease in pro-inammatory cytokines are two probable anti-inammatory mechanisms of fucoidan. TNF-α,
IL-1, and iNOS mRNA expression in M1 microglia was sig-
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nicantly reduced by fucoidan, but IL4, CD206, Arg1, and
TGF- mRNA expression in M2 microglia was signicantly
increased. Consequently, fucoidan has antioxidant and antiinammatory properties [102].
4.6.1.8 Cordyceps sinensis
Since more than a 1000 years ago, cordyceps, one of the
most prized traditional Chinese medicines, has been widely
utilized to treat and prevent many human illnesses. It is made
up of the dried Cordyceps sinensis fungus, which has
immune-boosting and antioxidative qualities and on which
caterpillar larvae develop. Through the transforming growth
factor 1 (TGF 1) pathway, cordyceps polysaccharides (CPS)
may lessen the production of ROS and lessen damage. TGF-1
and extracellular matrix (ECM) levels in patients may return
to normal under the inuence of CPS.CPS improved CRF
considerably and in a dose-dependent way [103].
4.6.1.9 Chinese Chive Polysaccharides
Chinese chive, also known as Allium tuberosum Rottl. Ex
Spreng, is a well-known culinary herb used in traditional
Chinese medicine to protect the kidneys. The Chinese chive
polysaccharides (CCP) were obtained through hot water
extraction. In a dose-dependent way, CCP greatly inhibited
the rise in TGF-levels in CRF animals, and TGF-mRNA
expression similarly decreased. According to this nding,
CCP may help those with chronic renal insufciency have
better renal function. The antioxidant, anti-inammatory,
and anti-brotic properties of CCP may potentially be
involved in the protective processes [104].
may cause a clinical are in IBD patients; however, it is
unknown how stress affects inammation. Despite some
research suggesting that smoking may be associated with a
decreased incidence of are-ups, smoking did not signicantly alter outcomes in people with ulcerative colitis.
Smoking increases the likelihood of corticosteroid dependency, accelerates the course of Crohn’s disease in patients,
and may even need surgery [106]. According to some
research, cannabis may help IBD patients with chronic pain
without having a major impact on biological remission.
However, the effects of alcohol and cannabis usage on IBD
patients are inconsistent [107]. Although these lifestyle variables may be changed, few interventional studies have been
carried out. Although a healthy lifestyle may help, studies of
organized exercise, psychological treatment, mindfulnessbased therapies like yoga and meditation, and IBD patients’
endoscopic or clinical disease activity have not always
improved with gut-directed hypnotherapy [108].
4.7.1 Polysaccharides Against IBS
4.7.1.1 Oat Bran Glucan
Oat (Avena sativa) bran, whose primary components are beta
1,3- and beta 1,4-glucan, signicantly reduced the dextran
sulfate sodium-induced (DSS) colitis mice model’s clinical
symptoms, weight loss, diarrhea, the inltration of inammatory cells, and increased colon length. In addition to lowering the levels of MPO, NO, and MDA, beta-glucan
administration also downregulates the expression of proinammatory markers in the colonic tissues [109].
4.7 Inammatory Bowel Syndrome
According to the location and intensity of the lesion, ulcerative colitis (UC) or Crohn’s disease can be classied as an
inammatory bowel syndrome (IBS) or irritable bowel disease (IBD). IBD symptoms include diarrhea, stomach discomfort, distension, and sometimes bloody stools. The two
regions with the highest rates of IBD are North America and
Europe, where it is estimated that 1.4 and 2.2 million people,
respectively, have CD and UC, and that more than 0.3% of
the population live in several European countries [105].
Numerous lifestyle choices, such as smoking, obesity,
stress, sleep disruption, and a lack of physical activity, may
increase the chance of developing IBS.Obesity increases the
likelihood of recurrence and is associated with higher levels
of anxiety, hopelessness, tiredness, and pain as well as higher
healthcare expenses. Additionally, obesity increases the
chance of therapy failure and adversely affects the pharmacokinetics of biological medicines. Independent of disease
activity, sleep disruption is quite common in IBD patients
and raises the chance of recurrence. Similarly, stress, especially perceived stress as opposed to signicant life events,
4.7.1.2 Mushroom Glucan
Mushrooms are used as food as well as a form of alternative
medicine and to reduce inammation since the dawn of time.
Patients with IBD have showed improvement in their inammatory symptoms after taking AndoSanTM, a mixed extract
from basidiomycetes mushrooms. The study also found that
calprotectin, an important indicator of inammation found in
the feces of UC patients, had reduced [110]. Another study
revealed that Chaga mushroom extract can shield IBD
patients’ lymphocytes’ DNA from oxidative degradation.
Another randomized placebo-controlled research found that
AndoSanTM had an anti-inammatory impact on individuals with both UC and CD.After being administered orally to
mice, Lentinus edodes beta-glucan had an anti-inammatory
effect. It also reduced the MDA and MPO levels in colonic
tissues and lowered the production of iNOS, TNF-α, IL-1,
and IL-6.Glucan decreased pro-inammatory factor synthesis, PPAR phosphorylation at Ser112 and Elk-1 phosphorylation at Ser84in a colitis model generated by DSS and in a
RAW264.7 cell model caused by LPS. This shows that a
sophisticated signaling network wasused by beta-glucan to
contribute in the anti-inammatory activity. Other researchers have shown that giving P. pulmonarius glucan to animals
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with colitis decreased their intestinal inammation and
related symptoms [111].
4.7.1.3 Seaweed-Derived β-Glucan
A research demonstrates that β-glucan derived from
Laminaria hyperborea and Laminaria digitata may both dramatically reduce the production of Th17-associated cytokines (IL-17a, IL-17F, and IL-22), as well as receptor IL23R
and IL-6, with no change to the TREG related targets. An
important focus for treating IBD’s underlying pathophysiology is the Th17 inammatory response. When administered
to pigs with DSS, the algal polysaccharide laminarin (containing β-glucan) alleviated clinical symptoms, body weight
loss, colonic Enterobacteriaceae, and a decrease in colonic
IL-6 mRNA expression level. But there has not yet been a
human clinical trial [111].
4.7.1.4 Fucoidan
Fucoidans are acidic, sulfated macromolecules consisting of
L-fucose and a variety of other oligosaccharides including
mannose, galactose, and xylose that are frequently recovered
from brown algae such as Fucus vesiculosus and the sporophyll of Undaria pinnatida. The oral treatment of fucoidan
considerably reduced the symptoms of colitis, and a histological investigation revealed a clear decrease in crypt architecture and goblet cells as well as immune cell inltration
and edema. These protective effects were veried by reducing the expression of 15 pro-inammatory cytokines in the
intestinal tissues. In pigs with DSS-induced colitis, a diet
high in fucoidan lowered the expression of IL-6 and improved
diarrhea and pathology scores. By lowering the expression of
the aP2 and PPAR genes, which in turn reduced the expression of genes associated with inammation, fucoidan also
suppressed fat storage. These data imply that fucoidan may
help reduce IBD-related symptoms [112].
4.7.1.5 Plantago Seeds Polysaccharides
Plantago ovata seeds and mesalazine (5-aminosalicylic acid)
were used in a clinical experiment on UC patients, and the
results were same for both. It improved intestinal cytoarchitecture in HLA-B27 transgenic rats given 5% Plantago ovata
seeds, and it reduced the production of pro-inammatory
cytokines such as NO, leukotriene B4, and TNF-α. It also
reduced colonic inammation. Compared to the control
group, rats receiving supplementation generated more
SCFAs. On colitis brought on by trinitrobenzenesulfonic
acid (TNBS), Plantago polysaccharides also show a comparable protective effect [113].
4.7.1.6 Wheat Bran andBarley
Whole grain cereals store a lot of arabinoxylans, and it has
been suggested that supplementing with them has biological
benetsfor IBS patients. In a clinical experiment involving
UC patients in remission, germinated barley (GB) was
employed, and it dramatically improved the disease index
and decreased the recurrence rate despite having no adverse
effects when compared to the control group [114].
4.7.1.7 Gums
Partially hydrolyzed guar gum (PHGG), an enzymeproduced water-soluble polysaccharide synthesized from
guar gum beans, decreased MPO activity, TNF-protein, and
mRNA expression in the colonic mucosa, and improved
colonic damage in mice with TNBS-induced colitis. PHGGfed mice showed considerably greater amounts of Clostridium
coccoides, Clostridium leptum, and Bacteroides fragilis,
according to an intestinal microbiota research [115]. Similar
to this, another study shown that giving animals with DSSinduced colitis a gum supplement—guar gum and PHGG—
signicantly decreased their clinical score. In a research
involving volunteers, the PHGG and fructooligosaccharides
(FOS) in the biscuits reduced the irritable bowel syndrome
symptoms of abdominal discomfort and loose stool [116].
According to these investigations, consuming PHGG may be
benecial for the creation of IBD treatments.
4.7.1.8 Pectins
A study looked at how wild jujube (Zizyphus spinosus Hu)
pulp polysaccharides (WJPs) affected an experimental IBD
model that was brought on by an intrarectal injection of
TNBS.WJPs are acidic heteropolysaccharides made up of
the remaining 60% of galactose and the remaining 40% of
arabinose glucose. WJPs were shown to dramatically
improve the condition in colitis rats by reducing weight loss,
disease activity index scores, and mucosal damage.
Additionally, WJPs downregulated the production of TNF-α,
IL-1, and IL-6 as well as MPO activity, which partially suppressed the inammatory response. In Caco-2 cells treated
with TNF, WJPs’ effect on TER and FITC-conjugated dextran permeability suggested that its protective effects on the
colon in colitis were connected to barrier function through
the activation of AMP-activated kinase (AMPK) activity.
67.3% anhydrogalacturonic acid and 38mg/g calcium make
up calcium pectate (CP), which has been researched for its
gastroprotective properties. Results showed that giving mice
CP (39.3kDa) made from citrus at dosages of 25 and 50mg/
kg considerably reduced the mean area of lesions and ulcers.
This preventive effect was even more effective than common
ulcer-treating drugs like famotidine [117].
4.8 Gastric andPeptic Ulcer
Due to the oversecretion of pepsin or stomach acid, an ulcer
forms on the inner lining of the gastrointestinal tract (GIT).
This is the most directly lifestyle-related disorder that also
has impression on metabolism. Very indisciplined food habit
is the main cause behind not only peptic ulcer, even gastric
ulcer too. Helicobacter pylori bacteria is the second cause of
ulceration but that is not linked to lifestyle habits. Fasting for
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more than 12 h after dinner and being very callous about
having early breakfast initiate ulceration day by day.
Continuous acid and enzyme secretion in an empty stomach
make the mucosal layer of GIT thinner each day and at a
certain point, the serous lining under the mucosa becomes
disclosed and very low pH gastric content makes wound on
it, which can occur both in the stomach and any other area of
the GIT [118]. Although ulcers can also be caused by dietary
components, a hypersecretory acidic environment, a stressful
environment, and other lifestyle factors like tobacco smoking, alcohol consumption, etc. [119]. The most common
symptoms of peptic ulcer are acute upper abdominal pain
while having food. Sometimes the upper abdominal pain is
relieved with eating, due to concomitant mucus secretion.
But the discomfort is frequently characterized as a burning
or aching sensation. Other symptoms include vomiting,
weight loss, and a lack of appetite. In certain cases, these
symptoms may be stomach bleeding, perforation, or obstruction. Obesity, smoking, and alcoholism also play vital roles
in the progression of ulcer. Obese people have an excess of
visceral adipose tissues that are metabolically active, which
may worsen the development of GIT inammation and
release of more pro-inammatory cytokines. As a result, it
has been hypothesized that obesity may affect peptic ulcer
disease [120]. The biggest risk factor that can be changed is
smoking. There is growing evidence connecting cigarette
smoking to gastrointestinal disorders, including chronic
inammation, GI tract cancers, and peptic ulcers [106].
Smoking decreases the level of epithelial growth factor
(EGF), leading to the prevention of mucosal cell proliferation. Smoking enhances gastric acid secretion and downregulates the production of bicarbonate anions. It causes pyloric
ineffectiveness and increases biliary reux, which allows
bile salts to damage the stomach mucosa, as well as reduces
the renewal of the epithelial cell line in GIT. Alcoholism
drastically reduces the activity of SOD, CAT, and GPx.
Additionally, it results in microcirculatory disruption, harms
the vascular endothelial cells in the stomach mucosa, and
causes hypoxia, which is brought on by an excess of oxygen
radicals [121].
4.8.1 Polysaccharides Against Ulcer
4.8.1.1 Sodium Alginate
Sodium alginate polysaccharides are hydrophilic, found in
marine algae and brown seaweed. It is biocompatible and
non-toxic. It has mucoadhesive properties and favorable biological properties also. The drug entrapment effectiveness of
oating microparticles is reported to be improved by sodium
alginate. By keeping the drug in the stomach for a long time
after administration, sodium alginate microbeads ensured a
totally aqueous environment, eliminating the need of organic
solvent in the preparation for the successful treatment of
peptic ulcer [122].
4.8.1.2 Ganoderma Lucidum Polysaccharide (GLP)
One of the primary sources of its pharmacological activity is
Ganoderma lucidum polysaccharide (GLP). Research on the
biological effects of GLP has focused on its antiinammatory, anti-tumor, antioxidant, anti-diabetic, and
immunomodulatory properties [41]. Antioxidant enzymes,
including SOD, GPX, and MPO, may be controlled in
alcohol- induced gastric damage treated by GLPs in rats, preserving the stomach tissue. In addition, GLPs can maintain
steady levels of EGF and signal molecule NO, protecting the
stomach mucosa from harm. TNF-α, IL-1, and IL-18 may be
inhibited by GLP, which would prevent the deterioration of
gastric damage. With a specic dose-dependent impact, all
three GLPs can dramatically lessen ethanol-induced acute
stomach damage in rats [123].
4.8.1.3 Pectic Polysaccharide
The natural food source of pectic polysaccharide (PP) is the
root of Decalepis hamiltonii, where PP is an arabinogalactantype polysaccharide. By enhancing gastric mucin formation
and providing cytoprotection to mucosal cells via a PGE2mediated route, PP dramatically increases endogenous PGE2
levels in the stomach. The exact pathway through which this
occurs is yet unknown though [124].
4.8.1.4 Fucoidan
A sulfated polysaccharide called fucoidan is produced from
the body walls of sea cucumbers and brown algae. By preventing changes in alanine aminotransferase, aspartate aminotransferase, IL-10, and IL-6, fucoidan can help prevent
stomach ulcers caused by aspirin. This suggests that fucoidan helps prevent inammatory cytokine-mediated oxidative
damage to the gastric mucosa [125].
4.8.1.5 Bletilla Polysaccharide
Bletilla striata, also known as Baiji in Chinese, is a signicant astringent hemostatic medicinal plant that has been used
for thousands of years to treat gastrointestinal ulcers, skin
and mucosal wounds, severe bleeding, hematemesis, and
hemoptysis [126]. Polysaccharides have the easy capacity to
gel at low pH levels, making them potentially effective antigastric ulcer medications. In gastric tissue, Bletilla striata
polysaccharide (BSP) may lower MDA and MPO levels
while increasing SOD activity. Through the antioxidant system, studies have shown that BSP has gastroprotective qualities that may reduce neutrophil hyperplasia and lipid
peroxidation brought on by high ROS levels. In ethanolinduced gastric ulcers, BSP has shown anti-inammatory
effects by inhibiting inammatory cytokine levels (TNF-α,
IL-1, IL-6, and IL-18) through MAPK/NF-κB pathway. BSP
pretreatment signicantly raised PGE2 levels. These suggest
that BSP may disrupt the control of stomach pH, mucus production, and gastric mucosal integrity [127].
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4.8.1.6 Arabinogalactan
A polymer called arabinogalactan is found in the cell walls
of higher plants. Additionally, it is a part of exudates and
gums. Fruits like the mango (Mangifera indica L) and
Lycium ruthenicum Murr also contain arabinogalactan. By
lowering acid and pepsin secretion, increasing mucous synthesis, and coating the mucosal membranes, arabinogalactan
can protect stomach tissue. Activating the TGF-β, the arabinogalactan protein from Jatropha curcas seed endosperm
was shown to stimulate cellular differentiation and mucosal
layer renewal and to promote gastric ulcer repair [128].
4.8.1.7 Rhamnogalacturonan
The polysaccharide named rhamnogalacturonan (RG) is
present in the leaves of the Acmella oleracea (L.) shrub,
known to the locals as jambu [129]. Using ethanol-induced
gastric lesions, the anti-ulcer efcacy of RG has been investigated. Through Toll-like receptor 4, RG stimulates dendritic cells, maturing their phenotype and activating the
mitogen-activated protein kinase (MAPK) signaling
cascade.
4.9 Gastroesophageal Reux Disease
The widespread medical illness called gastroesophageal
reux disease (GERD) is brought on by the irritating effect
of hydrochloric acid and other substances (such as pepsin)
found in stomach secretions that cause damage to the
esophageal mucosa. The esophageal epithelial lining cells
act as buffer against he stomach secretions. Heartburn, a
burning sensation in the chest that typically occurs after eating, is the predominant symptom of GERD [130]. GERD is
not a direct lifestyle metabolic disease, but disoriented lifestyle management may cause it sometimes. Obesity is sometimes linked to overeating, which results in stomach
distension and causes brief relaxations of the lower esophageal sphincter (LES). The distal esophageal epithelium of
obese people shows increased permeability, indicating a disturbed epithelial barrier, even in the absence of pathologic
reux. Metabolic consequences of central obesity may also
be involved [131]. Other potential risk factors for GERD
include dietary/lifestyle choices, alcohol consumption, and
cigarette smoking [132].
4.9.1 Polysaccharides Against GERD
4.9.1.1 Chitosan
Chitosan is a natural polysaccharide, mainly derived from
chitin. Chitosan-made microspheres showed extended drug
release and stayed buoyant for more than 11h [133].
4.9.1.2 Carbopol
Carbopol is a polymer that is pH dependent. As there is a
change in pH, a change in the state of Carbopol is observed.
Solution form can be noticed at acidic pH and at alkaline pH,
the solution gets changed into low viscosity gel. There are
some water-soluble polymers of Carbopol system [134].
4.9.1.3 Pectin
Pectin is the second-most used polymer in raft formation.
Pectin is typically extracted from plant cell walls and is also
an anionic polysaccharide. Divalent cations are responsible
for the conversion of pectin into the gel state in the stomach.
Calcium ions are also required to make the formulation that
forms a gel [135].
4.9.1.4 Starch
Jackfruit seeds are the source of the most prevalent polymer,
starch. Both carbs and protein are abundant in these seeds.
Two polysaccharides called amylose and amylopectin make
up the majority of starch. Utilizing an emulsion cross-linking
process, the starch microspheres can be made [136].
4.9.1.5 Alginates
Brown algae and certain bacteria produce alginate, which is
a phycocolloid and a microbial polysaccharide. Na alginate
can be used alone or in mixtures with magnesium (Mg) alginate, mannitol, sodium bicarbonate, potassium bicarbonate,
calcium carbonate, and other alginate preparations. Mg alginate is sometimes used in place of Na alginate in formulations. Without HCO3, alginate preparations prevent reux by
thickening the stomach’s contents, whereas with HCO3, alginate preparations neutralize stomach acid and create a “foam
raft” that oats on top of the stomach’s contents and prevents
reux [137].
4.9.1.6 Cashew Gum
The Anacardium occidentale L. tree yields cashew gum, a
biopolymer. Cashew gum can reduce the degradation of barrier function and inammatory episodes brought on by
reuxate contents into the esophageal mucosa in both
humans and animals with experimentally produced GERD,
and no hazardous indications were noted [138].
4.9.1.7 Pectin
After alginates, pectin is the biopolymer that has received the
most attention for its potential to produce rafts. Commercial
production uses citrus peels and apple pomace. The pectincontaining anti-reux formulation has effectively reduced
the moderate to severe heartburn and erosive esophagitis
returning with GERD and can be used as a maintenance therapy in patients with healed esophagitis. Additionally, it was
discovered that pectin reduced symptoms like nausea, nausea, and regurgitation [139].
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4.9.1.8 Guar Gum: Seed Gum
Guar gum is a polymer that is made from the Cyamopsis
tetragonolobus bean plant’s seed, gets dissolved in cold
water, and hydrates readily to form very viscous solutions at
low concentrations. These compounds are real emulsiers
since they demonstrate interfacial binding. When guar gum
and xanthan gum are mixed, viscosity synergism is demonstrated. Guar gum was utilized in an antacid preparation that
combined its raft-forming function with well-known antacids to create a protective coating [140].
4.9.1.9 Carrageenans: Seaweed Gum
As the carrageenan molecule contains up to 1000 galactose
residues, it is linear sulfated galactan derived from red seaweeds (Rhodophyceae). The three primary types of these are
typically dened as kappa, iota, or lambda. Additionally, the
fractions μ, η, and xi have been discovered. These types
exhibit different gelling properties despite being stable
across a wide pH range. Iota carrageenan gels are weaker
and less likely to synergize than kappa carrageenan gels, particularly when potassium ions are present. Lambda carrageenans bind strongly with proteins to create a pseudoplastic
thickening rather than gelling in water [141].
4.9.1.10 Plantago Polysaccharide
Isapgol (Plantago ovata) is a naturally occurring dietary
ber that is accessible locally and recognized by the Indian
Pharmacopeia. It is composed of polysaccharides and has
long been used as a bulk laxative. Its cytoprotective activity
has been supported by recent investigations. In an acidic
media, a viscous dispersion of isapgol husk in water transforms into a swelling gel-like substance. Isapgol was examined for its suitability as a raft-forming agent and was
discovered to be a strong contender for usage in the creation
of raft-forming antacid suspensions. However, substantial
clinical trials are required to determine this product’s invivo
effectiveness in the management of GERD [142].
The above polysaccharides are used in peptic ulcers and
other GIT disorders by the formation of Raft, a novel
approach to treating the problem of acidity and GERD
(shown in Fig.3).
4.10 Constipation
A typical gastrointestinal ailment known as constipation is
characterized by irregular bowel motions, or peristalsis (less
Fig. 3 Action of natural
polysaccharides on
gastrointestinal diseases
Irritable Bowel Syndrome
Pro-inflammatory
markers -
IL-1, IL-1, IL-6,
TNF-, LTB4
decreased
Inflammation
reduced
UIcerative
Colitis
NO, MDA & MPO
level decreased
Th17 mediated
inflammatory
markers (IL-17a, IL-F,
IL-22) reduced
Crohn’s
Disease
NATURAL POLYSACCHARIDES
Bowel movement
5HT4
Gel formation
(raft-formation)
Constipation
GERD
Gastric UIcer
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