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Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Astragalus membranaceus polysaccharide (APS) possesses excellent immunomodulatory activity. However, there are several studies on the structural characterization of APS. Here, we aimed to elucidate the repeating units of polysaccharides (APS1, 106.5 kDa; APS2, 114.5 kDa) obtained from different Astragalus membranaceus origins and further investigated their immunomodulatory activities. Based on structural analysis, types of the two polysaccharides were identified as arabinogalactan-I (AG-I) and arabinogalactan-II (AG-II), and co-elution of arabinogalactans (AGs) and α-glucan was observed. The backbone of AG-I was 1,4-linked β-Galp occasionally substituted by α-Araf at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Araf, which were attached to the O-3 of 1,6-linked β-Galp of the backbone. The presence of AGs in A. membranaceus was confirmed for the first time. The two polysaccharides could promote the expression of IL-6, IL-1β and TNF-α in RAW264.7 cells via MAPKs and NF-κB signaling pathways. The constants for APS1 and APS2 binding to Toll-like receptor 4 (TLR4) were 1.83 × 10 -5 and 2.08 × 10 -6 , respectively. Notably, APS2 showed better immunomodulatory activity than APS1, possibly because APS2 contained more AGs. Hence, the results suggested that AGs were the vital components of APS in the immunomodulatory effect., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Angelica sinensis polysaccharide (ASP) possesses diverse bioactivities; however, its metabolic fate following oral administration remains poorly understood. To intuitively determine its intestinal digestion behavior after oral administration, ASP was labeled with fluorescein, and it was found to accumulate and be degraded in the cecum and colon. Therefore, we investigated the in vitro enzymatic degradation behavior and identified the products. The results showed that ASP could be degraded into fragments with molecular weights similar to those of the fragments observed in vivo. Structural characterization revealed that ASP is a highly branched acid heteropolysaccharide with AG type II domains, and its backbone is predominantly composed of 1,3-Galp, →3,6)-Galp-(1→6)-Galp-(1→, 1,4-Manp, 1,4-Rhap, 1,3-Glcp, 1,2,3,4-Galp, 1,3,4,6-Galp, 1,3,4-GalAp and 1,4-GlcAp, with branches of Araf, Glcp and Galp. In addition, the high molecular weight enzymatic degradation products (ASP H) maintained a backbone structure almost identical to that of ASP, but exhibited only partial branch changes. Then, the results of ethanol-induced acute liver injury experiments revealed that ASP and ASP H reduced the expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and malondialdehyde (MDA) and increased the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels, thereby relieving ethanol-induced acute liver injury., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

It had been shown that lentinan (LNT) was mainly distributed in the liver after intravenous administration. The study aimed to investigate the integrated metabolic processes and mechanisms of LNT in the liver, as these have not been thoroughly explored. In current work, 5-([4,6-dichlorotriazin-2-yl] amino) fluorescein and cyanine 7 were used to label LNT for tracking its metabolic behavior and mechanisms. Near-infrared imaging demonstrated that LNT was captured mainly by the liver. Kupffer cell (KC) depletion reduced LNT liver localization and degradation in BALB/c mice. Moreover, experiments with Dectin-1 siRNA and Dectin-1/Syk signaling pathway inhibitors showed that LNT was mainly taken up by KCs via the Dectin-1/Syk pathway and promoted lysosomal maturation in KCs via this same pathway, which in turn promoted LNT degradation. These empirical findings offer novel insights into the metabolism of LNT in vivo and in vitro, which will facilitate the further application of LNT and other β-glucans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Polysaccharides have been widely used as biomaterials and drugs after oral administration due to their suitable physicochemical properties, good bioactivities and low toxicities. However, studies on their pharmacokinetics and absorption mechanism after oral administration are significantly restricted by the lack of polysaccharide detection methods. With the advancement of polysaccharide detection technologies such as immunoassays, fluorescent and isotopic labelling, the oral pharmacokinetics of polysaccharides have gradually been revealed. Here, paracellular pathway, transcellular pathways and M cell-mediated transport were analysed as mechanisms for oral absorption. The potential factors affecting the oral absorption of polysaccharides, including their charge, molecular weight, spatial structure and dose, as well as the species and physiological state of organisms, were analysed. Based on the absorption mechanism and influencing factors, we look forward to further investigating possible strategies for improving the oral absorption of polysaccharides., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum. Although galectin-3 (Gal-3) has been reported to play a proinflammatory role in UC, it is unknown whether pectic polysaccharide, a Gal-3 inhibitor in tumor metastasis, can alleviate UC by inhibiting Gal-3. The aim of this study was to investigate the anti-inflammatory effects and underlying mechanisms of SCLP, a pectic polysaccharide purified from Smilax china L. in our previous work, on dextran sulfate sodium-induced UC in BALB/c mice. The results showed that SCLP could significantly improve symptoms, alleviate histopathological damage and reduce the secretion of inflammatory mediators in mice with UC. Analysis of the anti-colitis mechanisms indicated that SCLP could inhibit the Gal-3/NLRP3 inflammasome/IL-1β pathway by suppressing the expression of Gal-3 and the interaction of Gal-3 and NLRP3. Our results suggested that SCLP could be a promising candidate for prevention and treatment of UC., (Copyright © 2021. Published by Elsevier Ltd.)

The elucidation of the oral absorption of natural polysaccharides contributes to their further research and utilization. Herein, to explore the absorption of a pectin-type polysaccharide from Smilax china L. (SCLP), SCLP was respectively fluorescently labeled with fluorescein-5-thioicarbazide (FSCLP) and Cyanine7 amine (Cy7-SCLP) for in vitro and in vivo tracking. The near-infrared imaging demonstrated that Cy7-SCLP was absorbable in the small intestine and distributed in the liver and kidney after oral administration. Subsequently, in vitro intestinal epithelial tissue experiments showed that the jejunum was the dominant site of FSCLP transport. Further transport studies in the Caco-2 cell monolayer illustrated that FSCLP was delivered across the monolayer via transcellular transport by caveolae-mediated endocytosis and macropinocytosis together with paracellular transport by reversibly affecting tight junctions. In summary, this work presents the oral absorption characteristics and mechanisms of SCLP through the intestinal epithelium, which will facilitate the further development of SCLP and pectin polysaccharides., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro. SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Lentinan (LNT), a typical triple helix β-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other β-glucans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Glycogen is a branched glucose polymer involved in sustaining blood glucose homeostasis. Liver glycogen comprises α particles (up to 300 nm in diameter) made of joined β particles (∼20 nm in diameter). Glycogen α particles in a mouse model for diabetes are molecularly fragile, breaking down into smaller β particles more readily than in healthy mice. Glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen degradation, is overexpressed in diabetic mice. This study shows that Metformin and Berberine, two common drugs, two common drugs used to treat diabetes, are able to revert the liver glycogen of diabetic mice to the stable structure seen in non-diabetic mice. It is also shown that these drugs reduce the GP level via the cAMP/PKA signaling pathway in diabetic livers and decrease the affinity of GP with the glycogen of db/db mice. These effects of these drugs may slow down the degradation of liver glycogen and improve glucose homeostasis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In recent years, the utilization of polysaccharides as targeted drug carriers has attracted considerable attention. Herein, Angelica sinensis polysaccharide (ASP), a plant polysaccharide with good biocompatibility, excellent aqueous solubility and intrinsic liver-targeted capability, was modified with hydrophobic group (deoxycholic acid) to fabricate amphiphilic conjugate (ASP-DOCA). Self-assembled nanoparticles were successfully developed for hepatoma-targeted delivery of therapeutic drug doxorubicin (DOX). The DOX loaded nanoparticles (DOX/ASP-DOCA NPs) were spherical in shape with a particle size of 228 nm and negatively charged around -17 mV. DOX was released from nanoparticles in a sustainable and pH-dependent manner. In vitro cellular uptake revealed that DOX/ASP-DOCA NPs were internalized into HepG2 cells through asialoglycoprotein receptor (ASGPR)-mediated endocytosis, resulting in a higher anti-proliferation effect than DOX-loaded dextran derivative DOX/DEX-DOCA NPs. Additionally, DOX/ASP-DOCA NPs showed higher inhibition on the growth of HepG2 multicellular spheroids (MCs) than DOX/DEX-DOCA NPs. In vivo imaging demonstrated that ASP-DOCA NPs specifically targeted HepG2 tumors via ASGPR, improving the accumulation of DOX/ASP-DOCA NPs in tumors and generating superior antitumor activity compared with free DOX and DOX/DEX-DOCA NPs. Taken together, ASP-DOCA NPs possess potential applications in drug delivery systems targeting liver cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A hyper branched (1→4)-α-d-glucan (RPS3) with degree of branching of 35% extracted from Rhizoma Panacis Japonici adopted a sphere-like conformation and showed little bioactivity. Three derivatives including sulfated (S-), phosphated (P-) and carboxymethylated (CM-) RPS3 were then synthesized and characterized by FTIR, (13)CNMR, and SEC-LLS-Vis-RI. As a result, the molecular weights of CM-RPS3, S-RPS3 and P-RPS3 decreased sharply in contrast to the original one, suggesting that chemical degradation has occurred. Moreover, the sphere-like conformation of RPS3 transferred into the random coil-like conformation according to the increased values of αη, αs and ρ. It was ascribed to the occurrence of the preferential degradation for the branches. In vitro and in vivo tests demonstrated that the negatively charged S-RPS3 and P-RPS3 with properly low molecular mass significantly inhibited H-22 tumor cells growth. This work offered valuable results for broadening the biological applications of α-d-glucans., (Copyright © 2014 Elsevier Ltd. All rights reserved.)