Next Article in Journal
Chemical Characterization and Bioactivities of Sericin Extracted from Silkworm Cocoons from Two Regions of Portugal
Previous Article in Journal
Extraction and Analysis of Phenolic Compounds from Rocket: Development of a Green and Innovative DES-Based Extraction Method
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 30
Issue 5
10.3390/molecules30051178
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging

by
Patricia Pantoja Newman
*,
Brenda Landvoigt Schmitt
,
Rafael Moura Maurmann
and
Brandt D. Pence
*
College of Health Sciences, University of Memphis, Memphis, TN 38152, USA
*
Authors to whom correspondence should be addressed.
Molecules 2025, 30(5), 1178; https://doi.org/10.3390/molecules30051178
Submission received: 12 December 2024 / Revised: 27 February 2025 / Accepted: 28 February 2025 / Published: 6 March 2025
Browse Figures
Versions Notes

Abstract

Aging is associated with a decline in physiological performance leading to increased inflammation and impaired immune function. Polysaccharides (PLs) found in plants, fruits, and fungi are emerging as potential targets for therapeutic intervention, but little is known about their effects on chronic inflammation and aging. This review aims to highlight the current advances related to the use of PLs, with the presence of arabinose, to attenuate oxidative stress and chronic and acute inflammation, and their immunomodulatory effects associated with antioxidant status in monocytes, macrophages, and neutrophil infiltration, and leukocyte rolling adhesion in neutrophils. In addition, recent studies have shown the importance of investigating the ‘major’ monosaccharide, such as arabinose, present in several of these polysaccharides, and with described effects on gut microbiome, glucose, inflammation, allergy, cancer cell proliferation, neuromodulation, and metabolic stress. Perspectives and opportunities for further investigation are provided. By promoting a balanced immune response and reducing inflammation, PLs with arabinose or even arabinose per se may alleviate the immune dysregulation and inflammation seen in the elderly, therefore providing a promising strategy to mitigate a variety of diseases.

Graphical Abstract

1. Introduction

Aging represents the major risk factor for infections and chronic disorders, including cancer, cardiovascular, neurodegenerative, and autoimmune diseases [1]. This biological process is characterized by the progressive decline in overall physiological homeostasis and performance, ultimately leading to death. Age-related changes in the immune system, termed as immunosenescence, have been implicated as central players in these processes, as chronic low-grade inflammation represents a common feature on aged tissues and age-related disorders [2,3]. In fact, this phenomenon, known as inflammaging, has been pointed out as a driver of metabolic diseases, autoimmunity, and frailty in the elderly, and has been correlated with increased morbidity and mortality [4,5]. The driver of inflammaging is mostly attributed to the dysregulation of adaptative immunity and the compensatory overactivation of innate immune responses combined with tissue damage accumulation [6]. In this regard, targeting these imbalanced mechanisms may be a promising strategy to control inflammation in aging.
In recent years, there has been a surge of research focused on polysaccharides (PLs) and their impact on chronic inflammation, which reflects an increasing awareness of their potential applications as therapeutic interventions. These bioactive molecules are found in plants, fungi, and algae and have been demonstrated to exert protective effects in inflammaging, as exemplified by recent studies with Radix astragali [7], Cannabis sativa [8], ginseng extract [9], and Ximenia americana [10]. More specifically, PLs have been associated with direct effects on immune function, as demonstrated by treatments with American ginseng root [11], Isatis root [12], Ganoderma sp. [13], and Astragalus sp. extracts [14]. In addition, PLs have been clinically tested for their excellent biocompatibility, structural stability, and biodegradability [15].
Despite current advances, the full elucidation of PLs’ biological properties, targets, and tissue interactions is still required [15]. In this regard, we will focus on examining the recent advances in PL treatments involving inflammaging and immune function. In addition, we intend to highlight the importance of arabinose, a monosaccharide, which is present in fungi [16], fruits [17], and plant extracts [18], and to delimit the current understanding of its therapeutic potential in monocytes and neutrophils.

2. Inflammaging and Innate Immune System

As described above, inflammaging is a state of chronically elevated inflammatory mediators observed in the serum of older adults, which differs from infection-related acute inflammatory states in that it is low-grade and sterile [3]. Increased levels of IL-1β, IL-6, TNFα, and C-reactive protein (CRP) are often described as markers of inflammaging [19], which can be traced to myeloid cells such as monocytes and macrophages [20]. Indeed, these innate immune cells have been speculated to be one of the major sources of pro-inflammatory cytokines in aged tissues [20,21]. The dysregulation of this immune compartment is mostly associated with the chronic, repetitive, lifelong antigenic stimulation by exogenous (e.g., pathogens) and endogenous (e.g., neoplastic cells and cellular debris) inflammatory stimuli, ultimately culminating in altered immune responses in older age [19]. In parallel, aged tissues accumulate senescent cells, which fuel the dysregulated inflammatory responses of innate immune cells through their constant secretion of cytokines and chemokines plus associated molecular damage mediators [22]. While other mechanisms have been implicated in the inflammaging development (e.g., gut leakage) [22], we aim here to summarize the age-related adaptations in the innate compartment that contribute to this phenomenon.
Monocytes and macrophages are key players involved in the production of inflammatory mediators in multiple contexts [21,23]. Aging in the monocyte population is described by an increased proportion of intermediate (CD14lowCD16+) and non-classical (CD14−CD16high) monocytes, characterized by a higher production of IL-1β, IL-6, and TNFα under basal conditions and up-stimulation [24,25]. Furthermore, monocytes isolated from aged individuals exhibit dysregulation of TLR-associated responses [24,26,27]. While TNFα and IL-6 are reduced upon TLR1/2 stimulation, the opposite is observed regarding TLR4 stimulation [26]. On the other hand, IL-8 production is higher after the stimulation of TLR1/2, TLR2/6, TLR4, or TLR5 [27]. These variable responses have been correlated with the altered downstream activation of MAPK and ERK1/2 pathways [26,27]. In addition, recent studies have also evidenced an association between defects in cellular metabolic processes and changes in immune function, as demonstrated by the co-occurrence of mitochondrial respiration impairment and abrogated monocyte LPS response in older adults [28,29].
Similarly, macrophages isolated from aged tissues exhibit metabolic alterations related to impaired immune function. For instance, NAD+ production declines in these cells, a molecule required for sirtuin activity, thus correlated with diminished SIRT2-dependent inflammasome inhibition and the increased activation of this pathway in aging [30,31]. In addition, the accumulation of dysfunctional mitochondria on aged macrophages has been directly correlated with the increased basal stimulation of the NLRP3 inflammasome and cGAS-STING pathways, driven by the cytoplasmic leakage of mitochondrial DNA and reactive oxygen species (ROS) [32,33,34]. Autophagy defects also contribute to enhancing endoplasmic reticulum (ER) stress and mitochondrial dysfunction, further leading to NLRP3 activation and increased expressions of IL-1β and IL-18 [35]. In fact, the inhibition of NLRP3 attenuates several age-related changes in macrophages that contribute to inflammaging [36]. Finally, it has recently been observed that aged macrophages exhibit increased cyclooxygenase 2 (COX2) expression and prostaglandin 2 (PGE2) production, which correlates with an increased expression of inflammatory cytokines such as TNFα and IL-6 [37].
Another key innate immune cell compartment is neutrophils, the first responders to infection. Neutrophils are components of the white blood cells responsible for defending our bodies against infection, constituting 60% to 70% of all leukocytes in human blood. Neutrophil recruitment is mediated by the release of damage-associated molecular patterns (DAMPs) from damaged cells or pathogen-associated molecular patterns (PAMPs) during infection [38]. Their recruitment contributes to tissue repairment, the phagocytosis of necrotic tissue, and the control of the recruitment of additional neutrophils. Monocytes/macrophages interact with neutrophils by releasing chemoattractants that recruit neutrophils to the site of inflammation. In a reverse mechanism, once neutrophils reach the site of inflammation, they recruit more monocytes and induce their differentiation into macrophages, increasing inflammation [39]. Neutrophils form neutrophil extracellular traps (NETs) as a defense mechanism, and NETosis leads to neutrophil death, exposing all neutrophil contents and increasing inflammation [40].
Aging is primarily associated with a defective migratory capacity in this population, which is attributed to the constitutive activation of the lipid kinase phosphoinositide 3-kinase (PI3K) [41]. This phenotype has been implicated in both reduced wound healing and in situ infection control due to decreased neutrophil recruitment [42]. In addition, diminished tissue egress is observed, which correlates with increased local inflammation, as demonstrated in burn-associated lung injury in aged mice [43]. Apart from defective migration, aged neutrophils display increased basal ROS, cytokine, and metalloproteinase production, associated with persistent nuclear factor kappa B (NF-kB) activation [44,45]. An increased proportion of these basally activated cells is further facilitated by impaired macrophage efferocytosis, which is required to remove senescent neutrophils from the circulation [46].

3. Polysaccharide Extraction, Separation, and Purification

As is known, PLs are distributed in plants, fungi, and algae. The extraction methods, separation, purification, and characterization potentiate the natural effect and increase the chances of developing new pharmacological targets. Huang and colleagues developed a guideline where common extraction methods using hot water, acid, or alkaline aqueous solution are the most useful extraction methods for PLs [47]. The PLs present in this review, as described in Table 1, are predominantly extracted using water, hot or cold. PLs such as Ximenia americana added steps for deproteinization intending to keep PLs less contaminated. Methods such as the DEAE-cellulose column, high-performance liquid chromatography (HPLC), and column chromatography are examples of techniques used to purify the PLs and even prepare fractions of the major monosaccharides present in a complex PL structure [47]. Table 1 shows the methods of extraction, separation, and purification used by the PLs discussed in this review, and the majority of PLs show the presence of arabinose in their structure.

4. Polysaccharides and Inflammaging

PLs have been recently demonstrated to exert distinct effects on the aging process. These complex carbohydrates found in plants, fungi, and algae have shown potential as anti-aging agents due to their antioxidant, immunomodulatory, and anti-inflammatory properties [71,72,73]. PLs, such as β-glucans and fucoidans, have been increasingly studied for their ability to delay and/or reverse age-related physiological decline [74]. PLs from Cardyceps cicadae [55], ginseng extract [9], Astragalus membranaceus, and Ganoderma lucidum are able to scavenge ROS and reduce oxidative damage, a major driver of aging [75]. Additionally, PLs possess anti-inflammatory properties, as exemplified by PLs extracts from Ximenia americana reducing IL-8 and leukocytes migration [18,76]. PLs from medicinal mushrooms and seaweeds have also demonstrated the ability to modulate immune function by enhancing the activity of macrophages and natural killer cells [77,78]. In summary, by promoting a balanced immune response, PLs may mitigate the immune dysregulation seen in the elderly.
On the other hand, PLs can act as immunomodulators by increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines. For instance, β-glucans from oats (Avena sativa) and mushrooms (G. lucidum, Lentinula edodes) have been shown to suppress the release of IL-6 and TNFα while promoting the production of anti-inflammatory cytokines such as IL-10 [79]. In addition to their anti-inflammatory properties, PLs from larch trees, Fucus vesiculosus, Undaria pinnatifida, Chondrus crispus [80], G. lucidum, Flammulina velutipes, and Sparassis crispa [81] and Cucurbita moschata [82], Amorphophallus konjac [70], and kappa-carrageenan [53] also support gut health by acting as prebiotics and promoting the growth of beneficial gut microbiota. This not only improves immune function but also reduces systemic inflammation [81], providing a multifaceted approach to managing inflammaging and extending health span.
Modulating immune function is another important role of PLs, orchestrated by interactions with specific pattern recognition receptors (PRRs) and TLR on immune cells [83,84]. PLs, as isolated from G. lucidum, enhanced immune activity by improving phagocytosis, regulating cytokine production and decreasing pro-inflammatory cytokines such as IL-6 and TNFα while promoting anti-inflammatory cytokines like IL-10 [85]. Wenfung Li and colleagues showed Astragalus sp. polysaccharide (APS) to exert anti-tumor activity by improving the phagocytosis of peritoneal macrophages and regulating cytokine production, denoted by decreased pro-inflammatory cytokines such as IL-2, TNFα, and interferon-γ (IFN-γ) [86]. This effect helps to protect tissues from damage and prevents chronic inflammation associated with age-related diseases, positioning PLs as potential therapeutic agents for managing inflammatory conditions while enhancing immune resilience and counteracting inflammaging.
From all the PLs presented in Table 2, 87% presented arabinose in their structures. Only 13% did not show the presence of arabinose, such as Amorphophallus konjac [70], Aparassis crispa [62], and Carrageenan [53]. Considering the PLs with arabinose in their structure, 60% show arabinose as the main or second main compound in their composition such as Ximenia americana [18], Saposhnikoviae radix [40], Ganoderma lucidum [48], and Fragaria x ananassa [67]. We will focus on PLs with the presence of arabinose on their structure, evaluating the interaction between monocytes and neutrophils and possible mechanisms involving arabinose as a pharmacological target.

5. Polysaccharide Interaction with Monocytes and Neutrophils

PLs from various natural sources, such as mushrooms, algae, and medicinal plants, have shown potential in modulating the activity of aged monocytes [85,104]. PLs, particularly from A. sative, Hordeum vulgare, and Reishi and Shiitake mushrooms, have been reported to reduce the production of pro-inflammatory cytokines and enhance the anti-inflammatory response of monocytes in aged individuals [58]. This immunomodulatory effect is linked to the activation of PRRs such as Dectin-1 on monocytes, which triggers an anti-inflammatory signaling pathway [83]. Studies with Fragaria x ananassa, Morus alba, and G. lucidum have shown that polysaccharides can reduce oxidative stress and promote the secretion of anti-inflammatory cytokines such as IL-10 in aged monocytes, thereby counteracting inflammaging and improving immune function [97,105].
As discussed above, one of the major challenges of aging is the declining ability of monocytes to respond appropriately to pathogens and tissue damage. PLs from Dendrobium spp. have been studied as potential agents for rejuvenating aged monocytes by enhancing their phagocytic activity and modulating cytokine secretion [99]. Similarly, PLs from mushrooms have been shown to modulate cytokine secretion at a level that initiates signaling cascades critical for immune responses [106]. For instance, fucoidan, a PL found in brown algae, has been shown to improve aged monocyte function by reducing the expression of pro-inflammatory genes and increasing anti-inflammatory signaling pathways [60,89]. Furthermore, PLs modulated the NF-κB signaling pathway, reducing excessive inflammation and ensuring a controlled immune response, especially in chronic inflammatory conditions [81]. These findings suggest that polysaccharides may help restore the immune balance in aging, promoting healthier aging and improved immune responses.
Given their ability to modulate aged monocytes and reduce inflammaging as described before, PLs have considerable potential as therapeutic agents for age-related immune dysfunction. In addition to acting as immunomodulators, PLs have antioxidant and tissue-regenerative properties that may further support the function of aging monocytes [70]. Clinical studies are exploring the use of PLs to reduce chronic inflammation in elderly patients, particularly in conditions such as cardiovascular disease, arthritis, and neurodegenerative disorders in which monocyte-driven inflammation plays a key role [86]. By targeting the underlying causes of monocyte aging and dysfunction, PLs may represent a novel class of immunomodulatory drugs aimed at promoting healthy aging and reducing the burden of age-related disease.
Over the past 20 years, several papers have described the mechanisms by which PLs coordinate neutrophil phenotype and function. Ming-Jen Hsu and colleagues showed that PLs from G. lucidum (PS-G) enhanced phagocytic activity through multiple signaling pathways, such as Protein kinase C (PKC), Src family, and p38-MAPK, and induced neutrophil migration in isolated cells and differentiated HL-60 [48]. Meanwhile, PLs from Rosa davurica (RDPA1) inhibited human neutrophil migration in vitro and impaired neutrophil infiltration in mouse peritonitis [49]. Similarly, PLs from Ximenia americana bark (TPL-Xa) reduced inflammation by reducing leukocyte rolling, adhesion, cytokine IL-8, and increased IL-4 in a murine model of gastritis [18].
PLs present in Astragalus sp. extract powder, commonly commercialized as bulk supplement, were demonstrated to control the neutrophil-to-lymphocyte ratio (NLR), a prognostic marker in patients with cancer receiving immunotherapy, decreasing NLR in 31.60% upon intravenous PG2, Astragalus sp. root PLs, and normalizing the NLR in patients with lung cancer in combination with immunotherapy [50]. Jie Zhang and colleagues tested PLs from Hedyotis diffusa (HDP) in acute lung injury induced by LPS and demonstrated attenuated in vivo inflammatory parameters, characterized by reduced IL-6 and TNFα levels, leukocyte counts, and NET formation [52]. Recently, root-derived PLs from Saposhnikoviae radix (SP40015A01) have been shown to improve neutrophil density and reduce inflammatory factor levels [40].

6. Arabinose: A Promising Anti-Inflammatory and Immunomodulatory Agent

The evidence presented above on how PLs, with the presence of arabinose, ameliorate inflammaging and modulate immune function brings us to the question of how the arabinose present in the PL itself could be involved in the healing process. Polysaccharides are chains of small molecules called monosaccharides. The most nutritionally important monosaccharides are those with pentoses and hexoses, i.e., molecules with five and six carbons in the backbone [107]. In the last 10 years, we have seen an increase in research on the effects of monosaccharides found in fruits, vegetables, and algae that can help prevent premature aging and its complications. The combination of monosaccharides such as D-arabinose and galactose inhibits peripheral inflammatory nociception in a mouse model [108], arabinoxylan, a combination of arabinose and xylose, reduced LPS-induced inflammation, and showed an immunomodulatory effect in RAW264.7 macrophage cells [109], and beet pulp rich in D-galacturonic acid and L-arabinose shows potential applications in diabetes, blood sugar regulation, and antimicrobials [110].
It is important to note that monosaccharides can form optically active stereoisomers, meaning that the direction of light determines whether the structure rotates to the right (D) or left (L), thus defining D or L stereoisomers [107]. It is a water-soluble aldose with an aldehyde group (-CHO) at the end of the molecule. A reducing reaction can bring the molecule to a primary alcohol, and under certain conditions, it can be isomerized to other sugars such as ribose or xylose [111,112].
Arabinose forms both D- and L-arabinose and has been studied for its pharmacological effects in various disease models such as metabolic syndrome [113,114,115], inflammation [116,117], food allergy [118], antioxidant [119], cancer [120], antidepression [121], and metabolic stress [122], as shown in Figure 1.
A review published by Csaba Fehér presented L-arabinose as a blood-sugar-reducing agent, an antioxidative agent with protective activities against hyperglycemia, and a precursor for antiviral drug development [123]. L-arabinose was administered for 6 weeks, and rats with high fat diet-induced metabolic syndrome had a marked reduction in body weight, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, total cholesterol, serum insulin, TNFα, and leptin [113]. Furthermore, L-arabinose also modulated gene-expression related to lipid metabolism and mitochondrial function in key metabolic tissues through the regulation of mice microbiota. It has also been shown to inhibit colitis through the microbiome modulation [114,115].
To understand the effect of arabinose on the immune system, Luyuan Kang and colleagues supplemented mice diets with L-arabinose in an LPS inflammatory model to evaluate intestinal inflammation [117]. They observed that L-arabinose downregulated serum TNFα, IL-1β, and IL-6 as well as gene expression levels of TNFα, IL-1β, IFN-γ, and TLR4 in the jejunum and colon and increased the concentration of short-chain fatty acids. Another study using L-arabinose pretreatment to attenuate gliadin-induced food allergy in mice showed that it improved the Th1/Th2 immune response imbalance based on the expression levels of key related cytokines and transcription factors in the small intestine and spleen of sensitized mice via regulation of tight junction proteins (TJ) and the suppression of p38-MAPK and p65/NF-κB inflammatory signaling pathways [118].
Recently, a switch between L- and D-arabinose has also been reported. Recent publications have shown the effect of D-arabinose on in vitro and in vivo mice models [118,120]. A publication by Tang and colleagues using an in vitro model of breast cancer showed that 50 mM of D-arabinose induced cytotoxicity modulated by autophagy and the p38-MAPK pathway [120]. Similarly, a mechanism of action of L-arabinose through the p38-MAPK regulation of T cells was reported by Wang et al. [118]. In tests with SH-SY5Y human neuroblastoma cells and the BV2 mouse microglial cell line in conjunction with behavioral tests, D-arabinose induced CREB regulated transcription coactivator 1 (CRTC1) expression through the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and transcription factor EB (TFEB) and also enhanced Acyl-coenzyme A synthetase short-chain family member 2 (ACSS2)-dependent CRTC1 transcription by activating AMP-activated protein kinase (AMPK) through the lysosomal AXIN-liver kinase B1 (LKB1) pathway [121].
Arabinose can be reduced to a sugar alcohol called arabitol [111] and has been shown to have anti-inflammatory effects. The presence of D-arabitol on the alkaloids SZ-A showed anti-inflammatory effects in macrophage cell line RAW 264.7 in an LPS-induced model [124], Li and colleagues showed that the effect of D-arabitol has ameliorated body weight fat gain, fat accumulation, insulin resistance, and gut microflora, indirectly promoting AMPK-PGC-1a-related white adipose tissue [125].

7. Future Perspectives

The papers summarized in this review are among the first to demonstrate that polysaccharides found in fungi [16], fruits [17], and plants [18] have therapeutic potential in monocytes and neutrophils through anti-aging, antioxidant, anti-inflammatory, and immunomodulatory activities [8,9,11,13,14]. However, there is still a promising opportunity to advance research. As mentioned above, the mechanisms of how the polysaccharides act in in vivo or in vitro are still unknown. Also, the monosaccharides, small molecules that make up the polysaccharide chain, have tremendous importance in their biological activity [117,119,120,121].
Additionally, as the evidence presented above, PLs are able to reduce pro-inflammatory cytokines secretion and expression [60,89,97], exert immunomodulatory effects [83], and enhance phagocytosis [99] and antioxidant status in monocytes and macrophages, key players involved in the production of inflammatory mediators in multiple contexts [21,23]. PLs have been shown to reduce key factors responsible for dysfunction in aged monocytes [58,97,105], although there are still inconclusive links between aging, chronic inflammation, and monocyte phenotypes that should be further investigated. PLs also showed effects on neutrophils, another key innate immune cell, such as reduced neutrophil migration through the p38-MAPK pathway [49], neutrophil infiltration [48], leucocyte rolling adhesion [18], an altered neutrophil-to-lymphocyte ratio [49], and reduced inflammatory parameters [50,52]. Notably, the mechanisms of PLs per se in monocytes and neutrophils, key cells involved in inflammaging, have the potential to ameliorate the chronic inflammation present in the elderly population.
The fact that the PLs are composed of monosaccharides raises the question of whether the major monosaccharides present in the PLs chain could act as an anti-inflammatory and immunomodulatory agent in chronic inflammation. Arabinose is a monosaccharide found in PLs derived from, for example, Ximenia americana [18], Ganoderma lucidum [49,79], hemp residues [8], ginseng [9], and Astragalus spp. [86] and has been shown to have pharmacological effects in several disease models including metabolic syndrome [113,114,115], inflammation [116,117], food allergy [118], antioxidant [119], cancer [120], and anti-depression [121].
Authors have published on PLs and pentose sugars, such as arabinose, highlighting the p38-MAPK pathway as a primary mechanism of action [49,118,120]. A reduced sugar alcohol called arabitol also showed indirect effects on the p38-MAPK pathway [124,125]. P38-MAPK directly influences innate immune cells by driving cellular responses related to ROS levels [126]. This perspective opens up opportunities to explore the modulation of monocytes and neutrophils in a series of tests focused on the ROS pathway. Additionally, experiments involving calcium signaling are viable, given that ROS inhibits calcium entry through the ORAI1 channel in monocytes or activates neutrophils through NFAT transcription [127].

8. Conclusions

In recent years, studies employing PLs and their major components, the monosaccharides, have shown advances in our knowledge of their impact on chronic inflammation and immunomodulation as presented above. However, when the focus turns to arabinose, a full understanding of the pharmacological effects on the innate immune system and the consequences for inflammaging are still open. Likewise, targeting inflammaging appears to be a promising strategy for treating age-related diseases and disorders. Understanding the mechanisms of PLs with arabinose or even arabinose per se could lead to the development of targeted therapeutics for a variety of age-related diseases.

Author Contributions

Conceptualization, P.P.N.; writing—original draft preparation, P.P.N., B.L.S. and R.M.M., writing—review and editing, B.D.P.; supervision, B.D.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Institute on Aging, grant number R15AG078906 to B.D.P.

Conflicts of Interest

The authors declare no conflicts of interest in this paper.

References

  1. Niccoli, T.; Partridge, L. Ageing as a Risk Factor for Disease. Curr. Biol. 2012, 22, R741–R752. [Google Scholar] [CrossRef] [PubMed]
  2. Furman, D.; Campisi, J.; Verdin, E.; Carrera-Bastos, P.; Targ, S.; Franceschi, C.; Ferrucci, L.; Gilroy, D.W.; Fasano, A.; Miller, G.W.; et al. Chronic Inflammation in the Etiology of Disease across the Life Span. Nat. Med. 2019, 25, 1822–1832. [Google Scholar] [CrossRef] [PubMed]
  3. Franceschi, C.; Garagnani, P.; Parini, P.; Giuliani, C.; Santoro, A. Inflammaging: A New Immune–Metabolic Viewpoint for Age-Related Diseases. Nat. Rev. Endocrinol. 2018, 14, 576–590. [Google Scholar] [CrossRef]
  4. Leng, S.X.; Cappola, A.R.; Andersen, R.E.; Blackman, M.R.; Koenig, K.; Blair, M.; Walston, J.D. Serum Levels of Insulin-like Growth Factor-I (IGF-I) and Dehydroepiandrosterone Sulfate (DHEA-S), and Their Relationships with Serum Interleukin-6, in the Geriatric Syndrome of Frailty. Aging Clin. Exp. Res. 2004, 16, 153–157. [Google Scholar] [CrossRef] [PubMed]
  5. Fülöp, T.; Dupuis, G.; Witkowski, J.M.; Larbi, A. The Role of Immunosenescence in the Development of Age-Related Diseases. Rev. Investig. Clin. 2016, 68, 84–91. [Google Scholar]
  6. Fulop, T.; Larbi, A.; Dupuis, G.; Le Page, A.; Frost, E.H.; Cohen, A.A.; Witkowski, J.M.; Franceschi, C. Immunosenescence and Inflamm-Aging as Two Sides of the Same Coin: Friends or Foes? Front. Immunol. 2018, 8, 1960. [Google Scholar] [CrossRef]
  7. Tang, Z.; Huang, G. Extraction, Structure, and Activity of Polysaccharide from Radix Astragali. Biomed. Pharmacother. 2022, 150, 113015. [Google Scholar] [CrossRef]
  8. Chang, T.; Li, H.; Lv, H.; Tan, M.; Hou, S.; Liu, X.; Lian, M.; Zhao, Q.; Zhao, B. Extraction, Physicochemical Properties, Anti-Aging, and Antioxidant Activities of Polysaccharides from Industrial Hemp Residues. Molecules 2022, 27, 5746. [Google Scholar] [CrossRef]
  9. Sun, J.; Zhong, X.; Sun, D.; Xu, L.; Shi, L.; Sui, J.; Liu, Y. Anti-Aging Effects of Polysaccharides from Ginseng Extract Residues in Caenorhabditis Elegans. Int. J. Biol. Macromol. 2023, 225, 1072–1084. [Google Scholar] [CrossRef]
  10. Bakrim, W.B.; Nurcahyanti, A.D.R.; Dmirieh, M.; Mahdi, I.; Elgamal, A.M.; El Raey, M.A.; Wink, M.; Sobeh, M. Phytochemical Profiling of the Leaf Extract of Ximenia americana Var. caffra and Its Antioxidant, Antibacterial, and Antiaging Activities In Vitro and in Caenorhabditis Elegans: A Cosmeceutical and Dermatological Approach. Oxid. Med. Cell Longev. 2022, 2022, 3486257. [Google Scholar] [CrossRef]
  11. Azike, C.G.; Charpentier, P.A.; Lui, E.M.K. Stimulation and Suppression of Innate Immune Function by American Ginseng Polysaccharides: Biological Relevance and Identification of Bioactives. Pharm. Res. 2015, 32, 876–897. [Google Scholar] [CrossRef]
  12. Wang, X.; Chen, Z.; Chen, T.; Li, X.; Huang, S.; Wang, H.; Tong, C.; Liu, F. Isatis Root Polysaccharide Promotes Maturation and Secretory Function of Monocyte-Derived Dendritic Cells. BMC Complement. Med. Ther. 2020, 20, 301. [Google Scholar] [CrossRef] [PubMed]
  13. Ren, L.; Zhang, J.; Zhang, T. Immunomodulatory Activities of Polysaccharides from Ganoderma on Immune Effector Cells. Food Chem. 2021, 340, 127933. [Google Scholar] [CrossRef] [PubMed]
  14. Li, C.; Liu, Y.; Zhang, Y.; Li, J.; Lai, J. Astragalus Polysaccharide: A Review of Its Immunomodulatory Effect. Arch. Pharm. Res. 2022, 45, 367–389. [Google Scholar] [CrossRef] [PubMed]
  15. Miao, T.; Wang, J.; Zeng, Y.; Liu, G.; Chen, X. Polysaccharide-Based Controlled Release Systems for Therapeutics Delivery and Tissue Engineering: From Bench to Bedside. Adv. Sci. 2018, 5, 1700513. [Google Scholar] [CrossRef]
  16. Ma, N.; Palanisamy, S.; Yelithao, K.; Talapphet, N.; Zhang, Y.; Dae-Hee, L.; Shin, I.; Lee, D.; You, S. Structural Properties and Immune-enhancing Activities of Galactan Isolated from Red Seaweed Grateloupia filicina. Chem. Biol. Drug Des. 2023, 102, 889–906. [Google Scholar] [CrossRef]
  17. Tang, Y.; Zhu, Z.-Y.; Liu, Y.; Sun, H.; Song, Q.-Y.; Zhang, Y. The Chemical Structure and Anti-Aging Bioactivity of an Acid Polysaccharide Obtained from Rose Buds. Food Funct. 2018, 9, 2300–2312. [Google Scholar] [CrossRef]
  18. da Silva Pantoja, P.; Assreuy, A.M.S.; Silva, R.O.; Damasceno, S.R.B.; Mendonça, V.A.; Mendes, T.S.; Morais, J.A.V.; de Almeida, S.L.; Teixeira, A.É.E.A.; de Souza, M.H.L.P.; et al. The Polysaccharide-Rich Tea of Ximenia Americana Barks Prevents Indomethacin-Induced Gastrointestinal Damage via Neutrophil Inhibition. J. Ethnopharmacol. 2018, 224, 195–201. [Google Scholar] [CrossRef]
  19. Franceschi, C.; Salvioli, S.; Garagnani, P.; de Eguileor, M.; Monti, D.; Capri, M. Immunobiography and the Heterogeneity of Immune Responses in the Elderly: A Focus on Inflammaging and Trained Immunity. Front. Immunol. 2017, 8, 982. [Google Scholar] [CrossRef]
  20. Sanada, F.; Taniyama, Y.; Muratsu, J.; Otsu, R.; Shimizu, H.; Rakugi, H.; Morishita, R. Source of Chronic Inflammation in Aging. Front. Cardiovasc. Med. 2018, 5, 12. [Google Scholar] [CrossRef]
  21. De Maeyer, R.P.H.; Chambers, E.S. The Impact of Ageing on Monocytes and Macrophages. Immunol. Lett. 2021, 230, 1–10. [Google Scholar] [CrossRef]
  22. Franceschi, C.; Garagnani, P.; Vitale, G.; Capri, M.; Salvioli, S. Inflammaging and ‘Garb-Aging’. Trends Endocrinol. Metab. 2017, 28, 199–212. [Google Scholar] [CrossRef]
  23. Park, M.D.; Silvin, A.; Ginhoux, F.; Merad, M. Macrophages in Health and Disease. Cell 2022, 185, 4259–4279. [Google Scholar] [CrossRef] [PubMed]
  24. Hearps, A.C.; Martin, G.E.; Angelovich, T.A.; Cheng, W.; Maisa, A.; Landay, A.L.; Jaworowski, A.; Crowe, S.M. Aging Is Associated with Chronic Innate Immune Activation and Dysregulation of Monocyte Phenotype and Function. Aging Cell 2012, 11, 867–875. [Google Scholar] [CrossRef] [PubMed]
  25. Belge, K.-U.; Dayyani, F.; Horelt, A.; Siedlar, M.; Frankenberger, M.; Frankenberger, B.; Espevik, T.; Ziegler-Heitbrock, L. The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF. J. Immunol. 2002, 168, 3536–3542. [Google Scholar] [CrossRef]
  26. van Duin, D.; Mohanty, S.; Thomas, V.; Ginter, S.; Montgomery, R.R.; Fikrig, E.; Allore, H.G.; Medzhitov, R.; Shaw, A.C. Age-Associated Defect in Human TLR-1/2 Function. J. Immunol. 2007, 178, 970–975. [Google Scholar] [CrossRef] [PubMed]
  27. Qian, F.; Wang, X.; Zhang, L.; Chen, S.; Piecychna, M.; Allore, H.; Bockenstedt, L.; Malawista, S.; Bucala, R.; Shaw, A.C.; et al. Age-associated Elevation in TLR5 Leads to Increased Inflammatory Responses in the Elderly. Aging Cell 2012, 11, 104–110. [Google Scholar] [CrossRef]
  28. Pence, B.D.; Yarbro, J.R. Aging Impairs Mitochondrial Respiratory Capacity in Classical Monocytes. Exp. Gerontol. 2018, 108, 112–117. [Google Scholar] [CrossRef]
  29. Saare, M.; Tserel, L.; Haljasmägi, L.; Taalberg, E.; Peet, N.; Eimre, M.; Vetik, R.; Kingo, K.; Saks, K.; Tamm, R.; et al. Monocytes Present Age-Related Changes in Phospholipid Concentration and Decreased Energy Metabolism. Aging Cell 2020, 19, e13127. [Google Scholar] [CrossRef]
  30. He, M.; Chiang, H.-H.; Luo, H.; Zheng, Z.; Qiao, Q.; Wang, L.; Tan, M.; Ohkubo, R.; Mu, W.-C.; Zhao, S.; et al. An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance. Cell Metab. 2020, 31, 580–591. [Google Scholar] [CrossRef]
  31. Minhas, P.S.; Liu, L.; Moon, P.K.; Joshi, A.U.; Dove, C.; Mhatre, S.; Contrepois, K.; Wang, Q.; Lee, B.A.; Coronado, M.; et al. Macrophage de Novo NAD+ Synthesis Specifies Immune Function in Aging and Inflammation. Nat. Immunol. 2019, 20, 50–63. [Google Scholar] [CrossRef] [PubMed]
  32. Lv, N.; Zhao, Y.; Liu, X.; Ye, L.; Liang, Z.; Kang, Y.; Dong, Y.; Wang, W.; Kolliputi, N.; Shi, L. Dysfunctional Telomeres through Mitostress-induced CGAS/STING Activation to Aggravate Immune Senescence and Viral Pneumonia. Aging Cell 2022, 21, e13594. [Google Scholar] [CrossRef]
  33. Zhong, W.; Rao, Z.; Xu, J.; Sun, Y.; Hu, H.; Wang, P.; Xia, Y.; Pan, X.; Tang, W.; Chen, Z.; et al. Defective Mitophagy in Aged Macrophages Promotes Mitochondrial DNA Cytosolic Leakage to Activate STING Signaling during Liver Sterile Inflammation. Aging Cell 2022, 21, e13622. [Google Scholar] [CrossRef]
  34. Kang, Y.; Zhang, H.; Zhao, Y.; Wang, Y.; Wang, W.; He, Y.; Zhang, W.; Zhang, W.; Zhu, X.; Zhou, Y.; et al. Telomere Dysfunction Disturbs Macrophage Mitochondrial Metabolism and the NLRP3 Inflammasome through the PGC-1α/TNFAIP3 Axis. Cell Rep. 2018, 22, 3493–3506. [Google Scholar] [CrossRef]
  35. Dai, J.; Zhang, X.; Li, L.; Chen, H.; Chai, Y. Autophagy Inhibition Contributes to ROS-Producing NLRP3-Dependent Inflammasome Activation and Cytokine Secretion in High Glucose-Induced Macrophages. Cell Physiol. Biochem. 2017, 43, 247–256. [Google Scholar] [CrossRef] [PubMed]
  36. Youm, Y.-H.; Grant, R.W.; McCabe, L.R.; Albarado, D.C.; Nguyen, K.Y.; Ravussin, A.; Pistell, P.; Newman, S.; Carter, R.; Laque, A.; et al. Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging. Cell Metab. 2013, 18, 519–532. [Google Scholar] [CrossRef] [PubMed]
  37. Minhas, P.S.; Latif-Hernandez, A.; McReynolds, M.R.; Durairaj, A.S.; Wang, Q.; Rubin, A.; Joshi, A.U.; He, J.Q.; Gauba, E.; Liu, L.; et al. Restoring Metabolism of Myeloid Cells Reverses Cognitive Decline in Ageing. Nature 2021, 590, 122–128. [Google Scholar] [CrossRef]
  38. Peiseler, M.; Kubes, P. More Friend than Foe: The Emerging Role of Neutrophils in Tissue Repair. J. Clin. Investig. 2019, 129, 2629–2639. [Google Scholar] [CrossRef]
  39. Herrero-Cervera, A.; Soehnlein, O.; Kenne, E. Neutrophils in Chronic Inflammatory Diseases. Cell Mol. Immunol. 2022, 19, 177–191. [Google Scholar] [CrossRef]
  40. He, X.; Fan, H.; Sun, M.; Li, J.; Xia, Q.; Jiang, Y.; Liu, B. Chemical Structure and Immunomodulatory Activity of a Polysaccharide from Saposhnikoviae Radix. Int. J. Biol. Macromol. 2024, 276, 133459. [Google Scholar] [CrossRef]
  41. Sapey, E.; Greenwood, H.; Walton, G.; Mann, E.; Love, A.; Aaronson, N.; Insall, R.H.; Stockley, R.A.; Lord, J.M. Phosphoinositide 3-Kinase Inhibition Restores Neutrophil Accuracy in the Elderly: Toward Targeted Treatments for Immunosenescence. Blood 2014, 123, 239–248. [Google Scholar] [CrossRef] [PubMed]
  42. Brubaker, A.L.; Rendon, J.L.; Ramirez, L.; Choudhry, M.A.; Kovacs, E.J. Reduced Neutrophil Chemotaxis and Infiltration Contributes to Delayed Resolution of Cutaneous Wound Infection with Advanced Age. J. Immunol. 2013, 190, 1746–1757. [Google Scholar] [CrossRef]
  43. Nomellini, V.; Brubaker, A.L.; Mahbub, S.; Palmer, J.L.; Gomez, C.R.; Kovacs, E.J. Dysregulation of Neutrophil CXCR2 and Pulmonary Endothelial ICAM-1 Promotes Age-Related Pulmonary Inflammation. Aging Dis. 2012, 3, 234–247. [Google Scholar]
  44. Fortin, C.F.; Larbi, A.; Lesur, O.; Douziech, N.; Fulop, T. Impairment of SHP-1 down-Regulation in the Lipid Rafts of Human Neutrophils under GM-CSF Stimulation Contributes to Their Age-Related, Altered Functions. J. Leukoc. Biol. 2006, 79, 1061–1072. [Google Scholar] [CrossRef]
  45. Khanfer, R.; Carroll, D.; Lord, J.M.; Phillips, A.C. Reduced Neutrophil Superoxide Production among Healthy Older Adults in Response to Acute Psychological Stress. Int. J. Psychophysiol. 2012, 86, 238–244. [Google Scholar] [CrossRef] [PubMed]
  46. Frisch, B.J.; Hoffman, C.M.; Latchney, S.E.; LaMere, M.W.; Myers, J.; Ashton, J.; Li, A.J.; Saunders, J.; Palis, J.; Perkins, A.S.; et al. Aged Marrow Macrophages Expand Platelet-Biased Hematopoietic Stem Cells via Interleukin-1B. JCI Insight 2019, 5, e124213. [Google Scholar] [CrossRef] [PubMed]
  47. Huang, X.; Ai, C.; Yao, H.; Zhao, C.; Xiang, C.; Hong, T.; Xiao, J. Guideline for the Extraction, Isolation, Purification, and Structural Characterization of Polysaccharides from Natural Resources. eFood 2022, 3, e37. [Google Scholar] [CrossRef]
  48. Hsu, M.; Lee, S.; Lee, S.T.; Lin, W. Signaling Mechanisms of Enhanced Neutrophil Phagocytosis and Chemotaxis by the Polysaccharide Purified from Ganoderma lucidum. Br. J. Pharmacol. 2003, 139, 289–298. [Google Scholar] [CrossRef]
  49. Tong, H.; Jiang, G.; Guan, X.; Wu, H.; Song, K.; Cheng, K.; Sun, X. Characterization of a Polysaccharide from Rosa Davurica and Inhibitory Activity against Neutrophil Migration. Int. J. Biol. Macromol. 2016, 89, 111–117. [Google Scholar] [CrossRef]
  50. Tsao, S.M.; Wu, T.C.; Chen, J.; Chang, F.; Tsao, T. Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy. Integr. Cancer Ther. 2021, 20, 1534735421995256. [Google Scholar] [CrossRef]
  51. Liu, A.; Yu, J.; Ji, H.; Zhang, H.; Zhang, Y.; Liu, H. Extraction of a Novel Cold-Water-Soluble Polysaccharide from Astragalus Membranaceus and Its Antitumor and Immunological Activities. Molecules 2017, 23, 62. [Google Scholar] [CrossRef]
  52. Zhang, J.; Huo, J.; Zhao, Z.; Lu, Y.; Hong, Z.; Li, H.; Chen, D. An Anticomplement Homogeneous Polysaccharide from Hedyotis diffusa Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Inhibits Neutrophil Extracellular Trap Formation. Phytomedicine 2022, 107, 154453. [Google Scholar] [CrossRef]
  53. Ma, C.; Li, Q.; Dai, X. Carrageenan Oligosaccharides Extend Life Span and Health Span in Male Drosophila Melanogaster by Modulating Antioxidant Activity, Immunity, and Gut Microbiota. J. Med. Food 2021, 24, 101–109. [Google Scholar] [CrossRef]
  54. Wang, Y.; Zeng, T.; Li, H.; Wang, Y.; Wang, J.; Yuan, H. Structural characterization and hypoglycemic function of polysaccharides from Cordyceps cicadae. Molecules 2023, 28, 526. [Google Scholar] [CrossRef]
  55. Zhu, Y.; Yu, X.; Ge, Q.; Li, J.; Wang, D.; Wei, Y.; Ouyang, Z. Antioxidant and Anti-Aging Activities of Polysaccharides from Cordyceps Cicadae. Int. J. Biol. Macromol. 2020, 157, 394–400. [Google Scholar] [CrossRef] [PubMed]
  56. Zhao, J.-L.; Zhang, M.; Zhou, H.-L. Microwave-Assisted Extraction, Purification, Partial Characterization, and Bioactivity of Polysaccharides from Panax Ginseng. Molecules 2019, 24, 1605. [Google Scholar] [CrossRef] [PubMed]
  57. Li, D.; Chen, M.; Meng, X.; Sun, Y.; Liu, R.; Sun, T. Extraction, Purification, Structural Characteristics, Bioactivity and Potential Applications of Polysaccharides from Avena sativa L.: A Review. Int. J. Biol. Macromol. 2024, 265, 130891. [Google Scholar] [CrossRef] [PubMed]
  58. Singh, R.P.; Bhardwaj, A. β-Glucans: A Potential Source for Maintaining Gut Microbiota and the Immune System. Front. Nutr. 2023, 10, 1143682. [Google Scholar] [CrossRef]
  59. Chikari, F.; Han, J.; Wang, Y.; Ao, W. Synergized Subcritical-Ultrasound-Assisted Aqueous Two-Phase Extraction, Purification, and Characterization of Lentinus Edodes Polysaccharides. Process Biochem. 2020, 95, 297–306. [Google Scholar] [CrossRef]
  60. Apostolova, E.; Lukova, P.; Baldzhieva, A.; Katsarov, P.; Nikolova, M.; Iliev, I.; Peychev, L.; Trica, B.; Oancea, F.; Delattre, C.; et al. Immunomodulatory and Anti-Inflammatory Effects of Fucoidan: A Review. Polymers 2020, 12, 2338. [Google Scholar] [CrossRef]
  61. Nam, H.-B.; Lee, K.H.; Yoo, H.Y.; Park, C.; Lim, J.-M.; Lee, J.H. Rapid and High-Yield Recovery of Sodium Alginate from Undaria pinnatifida via Microwave-Assisted Extraction. Processes 2024, 12, 208. [Google Scholar] [CrossRef]
  62. López-Hortas, L.; Caleja, C.; Pinela, J.; Petrović, J.; Soković, M.; Ferreira, I.C.F.R.; Torres, M.D.; Domínguez, H.; Pe-reira, E.; Barros, L. Comparative Evaluation of Physicochemical Profile and Bioactive Properties of Red Edible Seaweed Chondrus Crispus Subjected to Different Drying Methods. Food Chem. 2022, 383, 132450. [Google Scholar] [CrossRef] [PubMed]
  63. Zhao, R.; Hu, Q.; Ma, G.; Su, A.; Xie, M.; Li, X.; Chen, G.; Zhao, L. Effects of Flammulina velutipes Polysaccharide on Immune Response and Intestinal Microbiota in Mice. J. Funct. Foods 2019, 56, 255–264. [Google Scholar] [CrossRef]
  64. Hu, S.; Wang, D.; Zhang, J.; Du, M.; Cheng, Y.; Liu, Y.; Zhang, N.; Wang, D.; Wu, Y. Mitochondria Related Pathway is Essential for Polysaccharides Purified from Sparassis crispa Mediated Neuro-Protection against Gluta-mate-Induced Toxicity in Differentiated PC12 Cells. Int. J. Mol. Sci. 2016, 17, 133. [Google Scholar] [CrossRef] [PubMed]
  65. Jiao, X.; Li, F.; Zhao, J.; Wei, Y.; Zhang, L.; Wang, H.; Yu, W.; Li, Q. Structural Diversity and Physicochemical Properties of Polysaccharides Isolated from Pumpkin (Cucurbita moschata) by Different Methods. Food Res. Int. 2023, 163, 112157. [Google Scholar] [CrossRef]
  66. Chelliah, R.; Park, C.R.; Park, S.J.; Barathikannan, K.; Kim, E.J.; Wei, S.; Sultan, G.; Hirad, A.H.; Vijayalakshmi, S.; Oh, D.H. Novel Approach on the Evaluation of Enzyme-Aided Alkaline Extraction of Polysaccharide from Hordeum Vulgare Husk and Molecular Insight on the Multifunctional Scaffold. Int. J. Biol. Macromol. 2024, 278, 134153. [Google Scholar] [CrossRef] [PubMed]
  67. Nogata, Y.; Yoza, K.; Kusumoto, K.; Ohta, H. Changes in Molecular Weight and Carbohydrate Composition of Cell Wall Polyuronide and Hemicellulose during Ripening in Strawberry Fruit. Prog. Biotechnol. 1996, 14, 591–596. [Google Scholar] [CrossRef]
  68. Liao, B.-Y.; Zhu, D.-Y.; Thakur, K.; Li, L.; Zhang, J.-G.; Wei, Z.-J. Thermal and Antioxidant Properties of Polysaccharides Sequentially Extracted from Mulberry Leaves (Morus alba L.). Molecules 2017, 22, 2271. [Google Scholar] [CrossRef]
  69. Luo, A.; He, X.; Zhou, S.; Fan, Y.; Luo, A.; Chun, Z. Purification, Composition Analysis and Antioxidant Activity of the Polysaccharides from Dendrobium Nobile Lindl. Carbohydr. Polym. 2010, 79, 1014–1019. [Google Scholar] [CrossRef]
  70. Nie, R.; Zhang, Q.Y.; Feng, Z.Y.; Huang, K.; Zou, C.Y.; Fan, M.H.; Zhang, Y.Q.; Zhang, J.Y.; Li-Ling, J.; Tan, B.; et al. Hydrogel-Based Immunoregulation of Macrophages for Tissue Repair and Regeneration. Int. J. Biol. Macromol. 2024, 268, 131643. [Google Scholar] [CrossRef]
  71. Jiang, L.; Zhang, G.; Li, Y.; Shi, G.; Li, M. Potential Application of Plant-Based Functional Foods in the Development of Immune Boosters. Front. Pharmacol. 2021, 12, 637782. [Google Scholar] [CrossRef] [PubMed]
  72. Wang, Y.; Chen, R.; Yang, Z.; Wen, Q.; Cao, X.; Zhao, N.; Yan, J. Protective Effects of Polysaccharides in Neurodegenerative Diseases. Front. Aging Neurosci. 2022, 14, 917629. [Google Scholar] [CrossRef]
  73. Wang, H.; Ma, J.X.; Zhou, M.; Si, J.; Cui, B.K. Current Advances and Potential Trends of the Polysaccharides Derived from Medicinal Mushrooms Sanghuang. Front. Microbiol. 2022, 13, 965934. [Google Scholar] [CrossRef]
  74. Song, L.; Zhang, S. Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources. Biomolecules 2023, 13, 1600. [Google Scholar] [CrossRef] [PubMed]
  75. Deng, R.; Wang, F.; Wang, L.; Xiong, L.; Shen, X.; Song, H. Advances in Plant Polysaccharides as Antiaging Agents: Effects and Signaling Mechanisms. J. Agric. Food Chem. 2023, 71, 7175–7191. [Google Scholar] [CrossRef] [PubMed]
  76. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The Hallmarks of Aging. Cell 2013, 153, 1194–1217. [Google Scholar] [CrossRef]
  77. Abdala-Díaz, R.T.; Casas-Arrojo, V.; Castro-Varela, P.; Riquelme, C.; Carrillo, P.; Medina, M.Á.; Cárdenas, C.; Becerra, J.; Pérez Manríquez, C. Immunomodulatory, Antioxidant, and Potential Anticancer Activity of the Polysaccharides of the Fungus Fomitiporia Chilensis. Molecules 2024, 29, 3628. [Google Scholar] [CrossRef]
  78. Zhang, W.; An, E.K.; Park, H.B.; Hwang, J.; Dhananjay, Y.; Kim, S.J.; Eom, H.Y.; Oda, T.; Kwak, M.; Lee, P.C.W.; et al. Ecklonia Cava Fucoidan Has Potential to Stimulate Natural Killer Cells In Vivo. Int. J. Biol. Macromol. 2021, 185, 111–121. [Google Scholar] [CrossRef]
  79. Ferreira, S.S.; Passos, C.P.; Madureira, P.; Vilanova, M.; Coimbra, M.A. Structure–Function Relationships of Immunostimulatory Polysaccharides: A Review. Carbohydr. Polym. 2015, 132, 378–396. [Google Scholar] [CrossRef]
  80. Huang, X.; Nie, S.; Xie, M. Interaction between Gut Immunity and Polysaccharides. Crit. Rev. Food Sci. Nutr. 2017, 57, 2943–2955. [Google Scholar] [CrossRef]
  81. Huang, R.; Zhang, J.; Xu, X.; Sun, M.; Xu, L.; Kuang, H.; Xu, C.; Guo, L. The Multiple Benefits of Bioactive Polysaccharides: From the Gut to Overall Health. Trends. Food Sci. Technol. 2024, 152, 104677. [Google Scholar] [CrossRef]
  82. Liu, G.; Liang, L.; Yu, G.; Li, Q. Pumpkin Polysaccharide Modifies the Gut Microbiota during Alleviation of Type 2 Diabetes in Rats. Int. J. Biol. Macromol. 2018, 115, 711–717. [Google Scholar] [CrossRef]
  83. Brown, G.D.; Gordon, S. A New Receptor for β-Glucans. Nature 2001, 413, 36–37. [Google Scholar] [CrossRef] [PubMed]
  84. Goodridge, H.S.; Reyes, C.N.; Becker, C.A.; Katsumoto, T.R.; Ma, J.; Wolf, A.J.; Bose, N.; Chan, A.S.H.; Magee, A.S.; Danielson, M.E.; et al. Activation of the Innate Immune Receptor Dectin-1 upon Formation of a ‘Phagocytic Synapse’. Nature 2011, 472, 471–475. [Google Scholar] [CrossRef] [PubMed]
  85. Barbosa, J.R.; de Carvalho Junior, R.N. Polysaccharides Obtained from Natural Edible Sources and Their Role in Modulating the Immune System: Biologically Active Potential That Can Be Exploited against COVID-19. Trends. Food Sci. Technol. 2021, 108, 223–235. [Google Scholar] [CrossRef]
  86. Li, W.; Hu, X.; Wang, S.; Jiao, Z.; Sun, T.; Liu, T.; Song, K. Characterization and Anti-Tumor Bioactivity of Astragalus Polysaccharides by Immunomodulation. Int. J. Biol. Macromol. 2020, 145, 985–997. [Google Scholar] [CrossRef]
  87. Pozharitskaya, O.N.; Obluchinskaya, E.D.; Shikov, A.N. Mechanisms of Bioactivities of Fucoidan from the Brown Seaweed Fucus vesiculosus L. of the Barents Sea. Mar. Drugs 2020, 18, 275. [Google Scholar] [CrossRef] [PubMed]
  88. Han, Y.; Wu, J.; Liu, T.; Hu, Y.; Zheng, Q.; Wang, B.; Lin, H.; Li, X. Separation, Characterization and Anticancer Activities of a Sulfated Polysaccharide from Undaria pinnatifida. Int. J. Biol. Macromol. 2016, 83, 42–49. [Google Scholar] [CrossRef]
  89. Raj, P.P.; Gopal, R.K.; Sanniyasi, E. Investigating the Anti-Inflammatory and Anti-Arthritis Effects of Fucoidan from a Brown Seaweed. Curr. Res. Biotechnol. 2024, 7, 100220. [Google Scholar] [CrossRef]
  90. Kulshreshtha, G.; Burlot, A.-S.; Marty, C.; Critchley, A.; Hafting, J.; Bedoux, G.; Bourgougnon, N.; Prithiviraj, B. Enzyme-Assisted Extraction of Bioactive Material from Chondrus Crispus and Codium Fragile and Its Effect on Herpes Simplex Virus (HSV-1). Mar. Drugs 2015, 13, 558–580. [Google Scholar] [CrossRef]
  91. Premarathna, A.D.; Sooäär, A.; Ahmed, T.A.E.; Rjabovs, V.; Hincke, M.T.; Tuvikene, R. Isolation, Structural Characterization and Biological Activities of Polysaccharides from Chondrus Crispus. Food Hydrocoll. 2024, 154, 110131. [Google Scholar] [CrossRef]
  92. Alkhalaf, M.I. Chemical Composition, Antioxidant, Anti-Inflammatory and Cytotoxic Effects of Chondrus crispus Species of Red Algae Collected from the Red Sea along the Shores of Jeddah City. J. King Saud. Univ. Sci. 2021, 33, 101210. [Google Scholar] [CrossRef]
  93. Thi Nhu Ngoc, L.; Oh, Y.-K.; Lee, Y.-J.; Lee, Y.-C. Effects of Sparassis crispa in Medical Therapeutics: A Systemat-ic Review and Meta-Analysis of Randomized Controlled Trials. Int. J. Mol. Sci. 2018, 19, 1487. [Google Scholar] [CrossRef]
  94. Abuarab, S.F.; Talib, W.H. Immunomodulatory and Anticancer Activities of Barley Bran Grown in Jordan: An in Vitro and in Vivo Study. Front. Nutr. 2022, 9, 838373. [Google Scholar] [CrossRef]
  95. Brown, G.D.; Herre, J.; Williams, D.L.; Willment, J.A.; Marshall, A.S.J.; Gordon, S. Dectin-1 Mediates the Biological Effects of β-Glucans. J. Exp. Med. 2003, 197, 1119–1124. [Google Scholar] [CrossRef] [PubMed]
  96. Han, H.-S.; Shin, J.-S.; Song, Y.-R.; Rhee, Y.K.; Cho, C.-W.; Ryu, J.H.; Inn, K.-S.; Hong, H.-D.; Lee, K.-T. Immunostimulatory Effects of Polysaccharides Isolated from Young Barley Leaves (Hordeum vulgare L.) with Dual Activation of Th1 and Th2 in Splenic T Cells and Cyclophosphamide-Induced Immunosuppressed Mice. Int. J. Biol. Macromol. 2020, 147, 954–964. [Google Scholar] [CrossRef]
  97. Liu, C.J.; Lin, J.Y. Anti-Inflammatory and Anti-Apoptotic Effects of Strawberry and Mulberry Fruit Polysaccharides on Lipopolysaccharide-Stimulated Macrophages through Modulating pro-/Anti-Inflammatory Cytokines Secretion and Bcl-2/Bak Protein Ratio. Food Chem. Toxicol. 2012, 50, 3032–3039. [Google Scholar] [CrossRef]
  98. He, X.; Fang, J.; Ruan, Y.; Wang, X.; Sun, Y.; Wu, N.; Zhao, Z.; Chang, Y.; Ning, N.; Guo, H.; et al. Structures, Bioactivities and Future Prospective of Polysaccharides from Morus Alba (White Mulberry): A Review. Food Chem. 2018, 245, 899–910. [Google Scholar] [CrossRef]
  99. Lee, C.-T.; Kuo, H.-C.; Chen, Y.-H.; Tsai, M.-Y. Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential. Curr. Med. Chem. 2017, 25, 1663–1681. [Google Scholar] [CrossRef]
  100. Wei, W.; Feng, L.; Bao, W.-R.; Ma, D.-L.; Leung, C.-H.; Nie, S.-P.; Han, Q.-B. Structure Characterization and Immunomodulating Effects of Polysaccharides Isolated from Dendrobium Officinale. J. Agric. Food Chem. 2016, 64, 881–889. [Google Scholar] [CrossRef]
  101. Chua, M.; Chan, K.; Hocking, T.J.; Williams, P.A.; Perry, C.J.; Baldwin, T.C. Methodologies for the Extraction and Analysis of Konjac Glucomannan from Corms of Amorphophallus Konjac K. Koch. Carbohydr. Polym. 2012, 87, 2202–2210. [Google Scholar] [CrossRef]
  102. Dai, J.; Chen, J.; Qi, J.; Ding, M.; Liu, W.; Shao, T.; Han, J.; Wang, G. Konjac Glucomannan from Amorphophallus Konjac Enhances Immunocompetence of the Cyclophosphamide-induced Immunosuppressed Mice. Food Sci. Nutr. 2021, 9, 728–735. [Google Scholar] [CrossRef]
  103. Islam, F.; Labib, R.K.; Zehravi, M.; Lami, M.S.; Das, R.; Singh, L.P.; Mandhadi, J.R.; Balan, P.; Khan, J.; Khan, S.L.; et al. Genus Amorphophallus: A Comprehensive Overview on Phytochemistry, Ethnomedicinal Uses, and Pharmacological Activities. Plants 2023, 12, 3945. [Google Scholar] [CrossRef]
  104. Li, C.; Wu, G.; Zhao, H.; Dong, N.; Wu, B.; Chen, Y.; Lu, Q. Natural-Derived Polysaccharides from Plants, Mushrooms, and Seaweeds for the Treatment of Inflammatory Bowel Disease. Front. Pharmacol. 2021, 12, 651813. [Google Scholar] [CrossRef] [PubMed]
  105. Seweryn, E.; Ziała, A.; Gamian, A. Health-Promoting of Polysaccharides Extracted from Ganoderma Lucidum. Nutrients 2021, 13, 2725. [Google Scholar] [CrossRef] [PubMed]
  106. Zhang, J.-J.; Li, Y.; Zhou, T.; Xu, D.-P.; Zhang, P.; Li, S.; Li, H.-B. Bioactivities and Health Benefits of Mushrooms Mainly from China. Molecules 2016, 21, 938. [Google Scholar] [CrossRef]
  107. Stylianopoulos, C. Carbohydrates: Chemistry and Classification. Encycl. Hum. Nutr. 2013, 265–271. [Google Scholar] [CrossRef]
  108. Silva-Leite, K.E.S.; Assreuy, A.M.S.; Mendonça, L.F.; Damasceno, L.E.A.; Queiroz, M.G.R.; Mourão, P.A.S.; Pires, A.F.; Pereira, M.G. Polysaccharide Rich Fractions from Barks of Ximenia Americana Inhibit Peripheral Inflammatory Nociception in Mice. Rev. Bras. Farmacogn. 2017, 27, 339–345. [Google Scholar] [CrossRef]
  109. Mendis, M.; Leclerc, E.; Simsek, S. Arabinoxylan Hydrolyzates as Immunomodulators in Lipopolysaccharide-Induced RAW264.7 Macrophages. Food Funct. 2016, 7, 3039–3045. [Google Scholar] [CrossRef]
  110. Jansen, L.M.; Hendriks, V.C.A.; Bentlage, H.; Ranoux, A.; Raaijmakers, H.W.C.; Boltje, T.J. The Industrial Application Potential of Sugar Beet Pulp Derived Monosaccharides d-Galacturonic Acid and l-Arabinose. ChemBioChem 2024, 25, e202400521. [Google Scholar] [CrossRef]
  111. Nelson, D.L.; Cox, M. Lehninger Principles of Biochemistry, 7th ed.; Macmillan Learning: New York, UK, USA, 2017; ISBN 9781319150877. [Google Scholar]
  112. Méline, T.; Muzard, M.; Deleu, M.; Rakotoarivonina, H.; Plantier-Royon, R.; Rémond, C. d-Xylose and l-Arabinose Laurate Esters: Enzymatic Synthesis, Characterization and Physico-Chemical Properties. Enzym. Microb. Technol. 2018, 112, 14–21. [Google Scholar] [CrossRef]
  113. Hao, L.; Lu, X.; Sun, M.; Li, K.; Shen, L.; Wu, T. Protective Effects of L-Arabinose in High-Carbohydrate, High-Fat Diet-Induced Metabolic Syndrome in Rats. Food Nutr. Res. 2015, 59, 28886. [Google Scholar] [CrossRef] [PubMed]
  114. Zhao, L.; Wang, Y.; Zhang, G.; Zhang, T.; Lou, J.; Liu, J. L-Arabinose Elicits Gut-Derived Hydrogen Production and Ameliorates Metabolic Syndrome in C57BL/6J Mice on High-Fat-Diet. Nutrients 2019, 11, 3054. [Google Scholar] [CrossRef] [PubMed]
  115. Wang, Y.; Zhao, J.; Li, Q.; Liu, J.; Sun, Y.; Zhang, K.; Fan, M.; Qian, H.; Li, Y.; Wang, L. L-Arabinose Improves Hypercholesterolemia via Regulating Bile Acid Metabolism in High-Fat-High-Sucrose Diet-Fed Mice. Nutr. Metab. 2022, 19, 30. [Google Scholar] [CrossRef]
  116. Li, Y.; Pan, H.; Liu, J.; Li, T.; Liu, S.; Shi, W.; Sun, C.; Fan, M.; Xue, L.; Wang, Y.; et al. L-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice. J. Agric. Food Chem. 2019, 67, 13299–13306. [Google Scholar] [CrossRef] [PubMed]
  117. Kang, L.; Pang, J.; Zhang, X.; Liu, Y.; Wu, Y.; Wang, J.; Han, D. L-Arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through Reduced M1 Macrophage Polarization. J. Nutr. 2023, 153, 3327–3340. [Google Scholar] [CrossRef]
  118. Wang, Y.; Sun, J.; Xue, L.; Liu, J.; Nie, C.; Fan, M.; Qian, H.; Zhang, D.; Ying, H.; Li, Y.; et al. L-Arabinose Attenuates Gliadin-Induced Food Allergy via Regulation of Th1/Th2 Balance and Upregulation of Regulatory T Cells in Mice. J. Agric. Food Chem. 2021, 69, 3638–3646. [Google Scholar] [CrossRef]
  119. Song, Y.B.; Kim, B.; Choi, M.J.; Song, Y.O.; Cho, E.J. Protective Effect of Arabinose and Sugar Beet Pulp against High Glucose-Induced Oxidative Stress in LLC-PK1 Cells. Food Chem. 2012, 134, 189–194. [Google Scholar] [CrossRef]
  120. Tang, Z.; Song, H.; Qin, S.; Tian, Z.; Zhang, C.; Zhou, Y.; Cai, R.; Zhu, Y. D-Arabinose Induces Cell Cycle Arrest by Promoting Autophagy via P38 MAPK Signaling Pathway in Breast Cancer. Sci. Rep. 2024, 14, 11219. [Google Scholar] [CrossRef]
  121. Guo, Y.; Chen, N.; Zhao, M.; Cao, B.; Zhu, F.; Guo, C.; Shi, Y.; Wang, Q.; Li, Y.; Zhang, L. D-Arabinose Acts as Antidepressant by Activating the ACSS2-PPARγ/TFEB Axis and CRTC1 Transcription. Pharmacol. Res. 2024, 202, 107136. [Google Scholar] [CrossRef]
  122. Schmitt, B.L.; da Pantoja, P.S.; Pence, B.D. Arabinose Mitigate Metabolic Stress in Inflammaging. Innov. Aging 2024, 8, 1133. [Google Scholar] [CrossRef]
  123. Fehér, C. Novel Approaches for Biotechnological Production and Application of L-Arabinose. J. Carbohydr. Chem. 2018, 37, 251–284. [Google Scholar] [CrossRef]
  124. Cao, H.; Ji, W.; Liu, Q.; Li, C.; Huan, Y.; Lei, L.; Fu, Y.; Gao, X.; Liu, Y.; Liu, S.; et al. Morus alba L. (Sangzhi) alkaloids (SZ-A) Exert Anti-Inflammatory Effects via Regulation of MAPK Signaling in Macrophages. J. Ethnopharmacol. 2021, 280, 114483. [Google Scholar] [CrossRef] [PubMed]
  125. Li, X.; Huang, J.; Yun, J.; Zhang, G.; Zhang, Y.; Zhao, M.; Zabed, H.M.; Ravikumar, Y.; Qi, X. d-Arabitol Ameliorates Obesity and Metabolic Disorders via the Gut Microbiota–SCFAs–WAT Browning Axis. J. Agric. Food Chem. 2023, 71, 522–534. [Google Scholar] [CrossRef]
  126. Canovas, B.; Nebreda, A.R. Diversity and Versatility of P38 Kinase Signalling in Health and Disease. Nat. Rev. Mol. Cell Biol. 2021, 22, 346–366. [Google Scholar] [CrossRef]
  127. Clemens, R.A.; Lowell, C.A. CRAC Channel Regulation of Innate Immune Cells in Health and Disease. Cell Calcium 2019, 78, 56–65. [Google Scholar] [CrossRef]
Molecules 30 01178 g001
Figure 1. Effect of arabinose in different models.
Figure 1. Effect of arabinose in different models.
Molecules 30 01178 g001
Table 1. Polysaccharide’s extraction methods.
Table 1. Polysaccharide’s extraction methods.
NameExtraction/SeparationPurificationRef
Ximenia americanaExtracted with NaOH and mass spectrometry (GC-MS).Ethanol precipitation[18]
Saposhnikoviae Radix (SP40015A01)Extracted water extraction and DEAE-cellulose. Separation by high performance liquid chromatography (HPLC).Purified by a Sepharose CL-6B column[40]
Ganoderma lucidum
(PS-G)		Extracted with boiling water. Separation by alcohol and gel filtration Sephadex G 50 column.Purified by anion exchange chromatography with a column of DEAE-cellulose.[48]
Rosa davurica (RDPA1)Extraction in ethanol and distilled water. Separation by Sepharose CL-6B column (2.6 × 100 cm), eluted with 0.15 M NaCl.Purified by a Sepharose CL-6B column (2.6 × 100 cm), eluted with 0.15 M NaCl and DEAE-cellulose.[49]
Astragalus (PG-2)Extracted with hot water. Precipitation by ethanol.Purified by gel chromatography[50]
Astragalus
membranaceus		Extracted with cold water. Ethanol precipitation.Purified by DEAE-cellulose chromatography and a Sephadex G-100 column[51]
Hedyotis diffusa
(HD-PS-3)		Extracted with DEAE-52 cellulose column. Separation by NaCl solution.Purified by an ephacryl S-200 column and distilled water[52]
CarrageenanExtracted by Qingdao Bozhi Huili Biotechnology Co., Ltd., China. Qingdao Bozhi Huili Biotechnology Co., Ltd., Qingdao, China.Purified by Qingdao Bozhi Huili Biotechnology Co., Ltd., China[53]
Cordyceps cicadaeExtracted with hot water for 2 h with Sevag reagent. Dialysis.Purified by DEAE-52 column chromatography[54,55]
Panax ginsengExtracted with hot water with MAS-II. Ethanol precipitation.Purified by DEAE-cellulose chromatography[56]
Avena sativaExtracted with alkaline solution (NaOH) and ultrasound-assisted extraction. Ethanol precipitation.Purified by gas chromatography[57,58]
Lentinula edodesExtracted with subcritical water with ultrasound-assisted extraction. Ethanol precipitation.Purified by gas chromatography[59]
Fucus vesiculosusExtracted in acid conditions (0.1 M HCl). Ethanol precipitation.Purified by dialysis[60]
Undaria pinnatifidaExtracted with hot water with Sevag reagent. Ethanol precipitation.Purified by DEAE-52 column chromatography and Sephacryl S-400 gel[61]
Chondrus crispusExtracted with soxhlet extraction with diethyl ether. Ethanol precipitation.Purified by gas chromatography[62]
Flammulina velutipesExtracted with hot water. Ethanol precipitation.Purified by DEAE-cellulose chromatography[63]
Sparassis crispaExtracted in hot water with Sevag reagent. Ethanol precipitation.Purified by DEAE-52 column chromatography and a Sepharose G-100 column[64]
Cucurbita moschataExtracted with hot water for 4 h, HCl for 40 min, and NaOH for 10 min. Ethanol precipitation.Purified by a DEAE-Sepharose Fast Flow column and Toyopearl HW-65F column[65]
Hordeum vulgareExtracted with enzymatic alkaline extraction. Ethanol precipitation.Purified by high-performance liquid chromatography[66]
Fragaria x ananassaHot water with 0.05 M HCl. Ethanol precipitation.Purified by gel filtration chromatography[67]
Morus albaHot buffer, chelating agent, dilute alkali, and concentrated alkali. Ethanol precipitation.Purified by gas chromatography[68]
Dendrobium spp.Deionized water. Ethanol precipitation.Purified by DEAE-cellulose chromatography and a Sephadex G-200 column[69]
Amorphophallus konjacHot water with ethanol. Ethanol precipitation.Purified by dialysis and gel permeation chromatography[70]
Table 2. Polysaccharides properties and anti-inflammatory/immunomodulatory activity.
Table 2. Polysaccharides properties and anti-inflammatory/immunomodulatory activity.
NameSourceMolecular Weight (kDa)CompositionStructureMethodsModelEffectsRef.
* Ximenia
americana		BarkNot
described		Arabinose, Rhamnose,
Galactose,
Glucose, Xylose,
Manose		Not
described		Gastritis induced by indomethacin, histology, biochemical analysis, and intravital microscopyGastritis in mouseReduced neutrophil migration, pro-inflammatory cytokines, and microscope lesion[18]
** Saposhnikoviae radix (SP40015A0)Root
(Huacaosheng
Traditional Chinese Medicine Co., Hebei, China), named by Professor Zhang Yuan		970Rhamnose,
Galacturonic Acid,
Galactose, Arabinose		Composed of 3-α-GalAp, 2-α-GalAp, 2,3-β-GalAp, and 2,3-β-Galp and branched at C3 of 2,3-
β-GalAp and C3 of 2,3-β-Galp		Extraction, isolation, purification, structural analysis, neutrophils density, and inflammatory contentZebrafishImproved neutrophils density and reduced inflammatory factor content (cytokines and biochemistry analysis)[40]
* Ganoderma
lucidum
(PS-G)		Mushroom628–818Rhamnose
Arabinose
Xylose
Mannose
Glucose
Galactose		Composed of (1-6)-b-D-glucan, which contains a backbone chain of (1-3)-linked D-glucose residues,
five out of 16 D-glucose residues being substituted at O-6
positions with single D-glucosyl units		PS-G purification, neutrophil isolation and HL-60 differentiation, phagocytosis, PKC activity, immunoblotting, immunoprecipitation, and neutrophil transmigration assayIn vitroEnhance neutrophil function in phagocytosis and chemotaxis[48]
Rosa
davurica (RDPA1)		Rose
Native from
Eastern Asia		26.1Rhamnose, Arabinose, Mannose,
Glucose,
Galacturonic Acid		Not describedIsolation and purification, neutrophil isolation, transwell, migration and infiltration neutrophil, flow cytometry, and protein binding assaysIn vivo in mouse and in vitroInhibited in vitro migration of human neutrophils, impacted
the migratory behavior of neutrophils, reduced the migrated distance and aver-
age velocity of RDPA1-treated cells. Impaired in vivo
neutrophil infiltration in the peritonitis mice. Exhibited significant blocking capacity of the inter-
action between 2 integrins, and ICAM-1 evaluated and in vitro protein binding assay		[49]
* Astragalus
(PG-2)		Root
(PhytoHealth Corporation,
Taiwan, ROC)		301Glucose,
Arabinose,
Fucose,
Xylose,
Galactose		Composed of α-D-(1,4)-Glc and (1,6)-α-D-Glcp backbone and a branch point at O-6.Review of patients with lung cancer that used PG-2 as treatmentLung cancer patientsPG2 could normalize the neutrophil-to-lymphocyte ratio (NLR) in patients with lung cancer receiving immune inhibitor treatment[50]
* Astragalus
membranaceus		Herb12.3Glucose,
Arabinose,
Fucose,
Xylose,
Galactose		Composed of β-(1→4)-linked d-galactopyranosyl residuesLymphocyte subsets in blood, macrophage pinocytosis, and cytotoxicity assaysSpleen
lymphocytes and mouse tumor		Reduces IL-1B and TNFα and enhances T-cell and B-cell activity[51,75,86]
** Hedyotis diffusa
(HD-PS-3)		Herb
Chinese medicine		742.2Mannose,
Rhamnose,
Glucose,
Galactose,
Arabinose		Composed of →4,6)-α-Glcp-(1→, →3,4)-α-Glcp-(1→, →4)-
α-Glcp-(1→, →4,6)-α-Galp-(1→, →5)-α-Araf-(1→, α-Rhap-(1→, α-Araf-(1→, α-GlcpA-(1→, →4)-β-Manp-(1→,
β-Manp-(1→ and →3)-β-Manp-(1→		In vivo LPS-induced lung inflammation, histology, biochemistry, and immunoblottingMouseAttenuated LPS-induced lung injured and inflammatory parameters through inhibition of complement activation[52]
CarrageenanRed algae200–800Rhamnose,
Mannose,
Glucose, Fucose, Xylose		Composed of (1,3)-linked galactopyranose-4-sulphate and (1,4)-linked 3,6-anhydrogalactopyranose residuesBiochemistry analysis and intestinal microbiota analysisIn vivo mouseImproved fecundity, showed antioxidant effect, reduced MDA and repressed NF-kB gene, and increased diversity gut microbiota[53]
Cordyceps
cicadae		Fungi128Glucose,
Mannose,
Arabinose,
Galactose		Composed of β-glucans and heteropolysaccharidesAntioxidant activity assays (DPPH, hydroxyl radical, superoxide anion, FRAP) and cell-based studies (ROS, senescence markers), antioxidant enzyme activities, lipid peroxidation, histopathology, and behavioral changesMacrophage and mouseReduced pro-inflammatory cytokines (TNFα, IL-6) and enhanced macrophage phagocytosis and NK cell activity[54,55,81]
** Panax
ginseng		Root207Glucose,
Arabinose, Rhamnose,
Galactose		Composed of β-(1→3) and β-(1→6) linkagesAntibacterial activity assay, Western blot, cytokine assays, Caenorhabditis elegans using physiological, microbiomics, and transcriptomic approachesBacteria,
macrophages, Caenorhabditis elegans		Inhibited NF-kB and MAPK pathways and enhanced lymphocyte proliferation and cytokine production[9,56,81]
** Avena sativaOats134–4100Glucose,
Arabinose, Mannose		Composed of linear β-glucans with mixed β-(1→3) and β-(1→4) linkagesELISA to measure cytokines, flow cytometry to assess cell activation, and 16S rRNA sequencing to investigate gut microbiotaMacrophages and mouseReduced TNFα and IL-6, enhanced gut microbiota and immune response, and activated monocytes via dectin-1 receptors[57,58,79]
Lentinula edodesMushroom2.384–2.387Glucose, Mannose,
Xylose,
Galactose,
Arabinose		Composed of β-glucans with β-(1→3) and β-(1→6) linkagesCytotoxicity assays, flow cytometry, and immunofluorescence to assess cells activation and assessment of immune response markers in mouse blood and tissueMacrophages and mouseInhibited NF-kB pathway, enhanced macrophage activity, and activated monocytes, enhancing phagocytosis and cytokine production[59,79,85]
Fucus
vesiculosus		Brown
seaweed		735Galactose,
Glucose, Fucose, Xylose,
Arabinose		Composed of α-(1→3) and α-(1→4) linkagesCytokines assays, cell viability assay, Western blotting analysis, and RT-PCRMacrophages, microglial cells, and Caco-2 cellsReduced TNFα and IL-1B, activated dendritic cells, and activated monocytes[60,87]
Undaria
pinnatifida		Brown
seaweed		97.9Galactose,
Fucose, Xylose, Mannose,
Arabinose, Rhamnose		Composed of α-(1→3) and α-(1→4) linkagesCartilage and bone destruction, tissue infiltration with inflammatory cells, and cytokines assayT-cells, NK cells, mice, and breast cancer in ratsInhibited NF-kB pathway, enhanced NK cell activity, and activated monocytes[61,88,89]
Chondrus
crispus		Red
seaweed		0.12237Galactose,
Glucose, Xylose, Arabinose, Mannose		Composed of k- and γ-carrageenanEnhancement of macrophage activity and ELISAMacrophages and Caco-2 cellsReduced TNFα and IL-1B and enhanced macrophage activity[62,90,91,92]
Flammulina
velutipes		Mushroom7473.14Fucose, Glucose, Mannose,
Xylose,
Arabinose		Composed of β-glucansMTT assay, macrophage activity, cytokine assay, and antioxidant activityMacrophages and mouseReduced TNFα and IL-6 and enhanced T-cells activity[63,85]
Sparassis
crispa		Mushroom75Galactose, Rhamnose,
Mannose		Composed of β-glucans with β-(1→3) and β-(1→6) linkagesMitochondrial function, macrophage activity, anti-inflammatory, and antioxidant activityMacrophages and mouseInhibited NF-kB pathway and enhanced macrophage activity[64,93]
** Cucurbita
moschata		Pumpkin18Glucose,
Galactose,
Mannose,
Arabinose		Composed of α-(1→4)- linked galacturonic acid residuesIntragastric injection of polysaccharide, 16S rRNA gene sequencing, and analysis of SCFARatsModulated gut microbiota and enhanced gut-associated lymphoid tissue[65,82]
** Hordeum
vulgare		Cereal grain0.2120885Glucose, Xylose, ArabinoseComposed of linear β-(1→3) and β-(1→4) linkagesAntioxidant activity, gut microbiota modulation, cytokine measurement, antibody production, and histopathological analysisMacrophages and mouseReduced TNFα and IL-6, modulated gut microbiota, and activated monocytes via dectin-1 receptors[66,94,95,96]
* Fragaria
x ananassa		Strawberry<50Glucose,
Galactose,
Arabinose,
Xylose,
Rhamnose		Composed of backbone of α-(1→4) linked galacturonic acid residuesPro-/anti-inflammatory cytokine levels secreted by LPS-stimulated macrophages cultured
with SP and MP for 48 h were determined using ELISA method to evaluate anti-inflammatory
effects of SP and MP. The Bcl-2/Bak (anti-/pro-apoptotic) protein levels in the cells were determined using
Western blotting method to evaluate anti-apoptotic effects		MacrophagesReduced TNFα and IL-1B and enhanced macrophage activity[67,97]
* Morus albaMulberry1.408–7.812Glucose,
Galactose,
Arabinose,
Xylose,
Rhamnose,
Mannose		Composed of various glycosidic linkagesPro-/anti-inflammatory cytokine levels secreted by LPS-stimulated macrophages cultured
with SP and MP for 48 h were determined using ELISA method to evaluate anti-inflammatory
effects of SP and MP. The Bcl-2/Bak (anti-/pro-apoptotic) protein levels in the cells were determined using
Western blotting method to evaluate anti-apoptotic effects		MacrophagesReduced TNFα and IL-6 and enhanced macrophage activity[68,97,98]
Dendrobium spp.Orchid136Glucose,
Galactose,
Arabinose,
Xylose,
Rhamnose,
Mannose		Composed of glucomannans with β-(1→4)-linked backbonesCell culture-based assays to evaluate cell viability, anti-inflammatory effects, antioxidant activity, enzyme inhibition, pharmacokinetics, and toxicity assaysMacrophages and mouseInhibited NF-kB pathway, enhanced T-cell activity, and activated monocytes and cytokine production[69,99,100]
Amorphophallus konjacKonjac≈1400–950Glucose,
Mannose		Composed of β-(1→4)-linked D-mannose and D-glucose units with acetyl groupsAnalysis of NK cell lethality, cell proliferation, pinocytic activity of mouse macrophages, serum levels, cytokines assay, and protein levels assayMacrophages and mouseReduced TNFα, IL-1B, and IL-6, inhibited NF-kB and MAPK pathway, and enhanced macrophage activity[101,102,103]
* arabinose as a major compound; ** arabinose as a second major compound.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Newman, P.P.; Schmitt, B.L.; Maurmann, R.M.; Pence, B.D. Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging. Molecules 2025, 30, 1178. https://doi.org/10.3390/molecules30051178

AMA Style

Newman PP, Schmitt BL, Maurmann RM, Pence BD. Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging. Molecules. 2025; 30(5):1178. https://doi.org/10.3390/molecules30051178

Chicago/Turabian Style

Newman, Patricia Pantoja, Brenda Landvoigt Schmitt, Rafael Moura Maurmann, and Brandt D. Pence. 2025. "Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging" Molecules 30, no. 5: 1178. https://doi.org/10.3390/molecules30051178

APA Style

Newman, P. P., Schmitt, B. L., Maurmann, R. M., & Pence, B. D. (2025). Polysaccharides with Arabinose: Key Players in Reducing Chronic Inflammation and Enhancing Immune Health in Aging. Molecules, 30(5), 1178. https://doi.org/10.3390/molecules30051178

Article Metrics

Back to TopTop