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Natural polysaccharides exhibit a wide range of biological activities, which are closely related to their structural characteristics, including their molecular weight distribution, size, monosaccharide composition, glycosidic bond types and spatial conformation, etc. Size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4), as two potent separation techniques, both harbor potential for continuous development and enhancement. This manuscript reviewed the fundamental principles and separation applications of SEC and AF4. The structural information and spatial conformation of polysaccharides can be obtained using SEC or AF4 coupled with multiple detectors. In addition, this manuscript elaborates in detail on the shear degradation of samples such as polysaccharides separated by SEC. In addition, the abnormal elution that occurs during the application of the two methods is also discussed. Both SEC and AF4 possess considerable potential for ongoing development and refinement, thereby offering increased possibilities and opportunities for polysaccharide separation and characterization., 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. Published by Elsevier B.V.)

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.)

Acute alcoholic liver injury (AALI) is a threat to human health. Dendrobium officinale polysaccharide (DOP) has the potential to protect the liver by enhancing the anti-oxidative system to maintain the relative balance of ROS (active oxygen species) and antioxidants in AALI mice. However, the dynamic improvement effect of DOP on AALI is still not clear and accurate medication guidance is not available, which limits the clinical application of DOP. Because of the advantages of high sensitivity, noninvasiveness, and visualization, near-infrared (NIR) fluorescence imaging has been widely studied in biochemistry and biomedicine. As the glutathione (GSH) level in the liver is closely related to the progression of AALI, herein, an NIR fluorescent probe for GSH, HCG was used to dynamically evaluate the effect of DOP on AALI mice. In this study, DOP was proven to maintain the relative balance of GSH content in the liver to protect it from damage. To the best of our knowledge, it is the first time to assess the effect of DOP on AALI mice through a NIR fluorescence imaging technique. This study may also provide a potential NIR imaging agent for the clinical research to improve the management of liver injury-related diseases., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Due to their good physicochemical properties, high biocompatibility and low toxicity, polysaccharides have been widely used as biomaterials in the fields of medicine and biology. However, in vivo investigations of their pharmacokinetics are significantly restricted by the difficulty in detection of polysaccharides. To date, polysaccharide labeling has become one of the most promising approaches for tracking polysaccharides in vivo. Here, we review fluorescent and radioisotopic labeling methods for polysaccharides and their applications in tracking polysaccharides in vivo, and compare the advantages and disadvantages of different labeling methods. The potential factors affecting the pharmacokinetics of polysaccharides in vivo were summarized, including the monosaccharide composition, charge, molecular weight and dosage of polysaccharides, as well as the physiological state of the organism. This review also prospects the applications of polysaccharides in medicine based on the reported pharmacokinetic characteristics in vivo., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Angelica sinensis polysaccharide (ASP) has hepatoprotective effects in liver injury models. However, its role and mechanism in chronic liver fibrosis have not been fully elucidated. In this study, a carbon tetrachloride (CCl 4 )-induced chronic liver fibrosis mouse model was established. The results showed that ASP treatment reduced serum alanine aminotransferase by approximately 50% and liver fibrosis areas by approximately 70%. Hepatic stellate cell (HSC) activation was inhibited in ASP-treated mice. Furthermore, the mechanism was studied in-depth, focusing on the interleukin 22/signal transducer and activator of transcription 3 (IL-22/STAT3) axis. Concentrations of 50 μg/ml and 100 μg/ml ASP induced the secretion of IL-22 in vitro, which further increased at a concentration of 200 μg/ml. Moreover, in vivo data showed that ASP significantly promoted IL-22 production in splenocytes and liver tissues. The antifibrotic effects of ASP were abolished after IL-22 neutralization. In addition, ASP activated the STAT3 pathway in the liver, as demonstrated by a 2-fold increase compared to that of the CCl 4 group, which was abrogated by the IL-22 antibody. Subsequently, we showed that the antifibrotic effects of ASP were abrogated by blocking STAT3 with S3I-201. In conclusion, ASP effectively alleviates chronic liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway., Competing Interests: Declaration of competing interest All the authors declared no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

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.)

Studies have confirmed that Angelica sinensis , which is a famous medicinal food in China, can effectively alleviate the symptoms of ulcerative colitis (UC) in rats. However, as the major water-soluble ingredient, the specific effects of A. sinensis polysaccharide (ASP) on UC and potential mechanisms were uncertain. In this study, we aimed to elucidate the protective effects of ASP on dextran sulfate sodium (DSS)-induced UC and to further explore the mechanisms. ASP could significantly ameliorate the symptoms of weight loss, disease activity index score, and colon shortening caused by DSS. ASP treatment also significantly suppressed the myeloperoxidase activity in colon tissues. Furthermore, after ASP administration, the expression of the proinflammatory cytokines (interleukin [IL]-6, IL-1 β , and tumor necrosis factor alpha) induced by DSS was remarkably suppressed, and there was a definite improvement in the expressions of tight junction proteins, such as zona occludens 1, occludin, and claudin-1. In addition, the results of apoptosis experiments showed that the apoptotic events were noticeably reduced after ASP treatment. Taken together, these results suggested that ASP may be a potential natural agent against UC.

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver-targeting drug delivery carrier with applications in acute alcoholic liver damage (ALD). Amphipathic cholesteryl hemisuccinate-ASP (ASP-CHEMS) conjugate was synthesized by an esterification reaction and characterized by conventional methods. ASP-CHEMS self-assembled nanoparticles (ACNPs) and Curcumin-loaded ACNPs (Cur/ACNPs) were fabricated with a roughly spherical shape, and their sizes were ranged from 200 to 260 nm in aqueous solution. Compared with free Cur, Cur/ACNPs displayed enhanced solubility, good photostability, and a sustained release of Cur over 72 h. In the in vivo cellular uptake behavior study and in vivo bioimaging experiments, the ACNPs showed excellent liver-targeting capability because of the specific recognition by the asialoglycoprotein receptor (ASGPR) overexpressed on the hepatocyte membrane. The tissue distribution of Cur/ACNPs in mice further demonstrated that ACNPs could distinctly enhance the distribution of Cur into the liver. Furthermore, Cur/ACNPs protected the liver from acute ALD by attenuating oxidative stress and were superior to the protective effects of free Cur and the Cur-loaded CHEMS modified-dextran derivative. According to the results, ACNPs may serve as a promising liver-targeting drug delivery carrier for liver disease prevention., 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 © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dendrobium officinale polysaccharide (DOP) is the main active ingredient of Dendrobium officinale Kimura & Migo, which is a precious traditional Chinese medicine and often used in treatment of hepatitis, diabetes, obesity and rheumatoid arthritis., Aim of the Study: DOP exhibits significant hypoglycemic activity, while its mechanism remains unclear. The present study aims to investigate the hypoglycemic mechanisms of DOP based on the glucagon-mediated signaling pathways and the liver glycogen structure, which catalyze hepatic glucose metabolism, and provide new knowledge about the antidiabetic mechanism of DOP and further evidence for its clinical use for diabetes., Materials and Methods: DOP were obtained from the dry stems of Dendrobium officinale by water extraction and alcohol precipitation method. T2DM mice model was established by high-fat diet combined with streptozotocin. Liver histopathological changes were observed by H&E and PAS straining. Pancreatic histology was studied by H&E staining and immunofluorescence analysis. The levels of glucagon and insulin were detected by Elisa Kit and the hepatic glycogen content was detected by GOPOD. The expressions of the hepatic glycogen-related metabolism enzymes, hepatic gluconeogenesis enzymes, and the related protein in cAMP-PKA and Akt/FoxO1 signaling pathways were detected by western blots. Liver glycogen was extracted from the liver tissues by sucrose density gradient centrifugation, and size exclusion chromatography (SEC) was used to analyze the structure of liver glycogen., Results: DOP could significantly affect the glucagon-mediated signaling pathways, cAMP-PKA and Akt/FoxO1, to further promote hepatic glycogen synthesis, inhibit hepatic glycogen degradation and hepatic gluconeogenesis. Moreover, DOP could reverse the instability of the liver glycogen structure and thus probably suppressed glycogen degradation. Thus, DOP finally would ameliorate hepatic glucose metabolism via glucagon-mediated signaling pathways and modifying liver-glycogen structure in diabetic mice., Conclusions: The hypoglycemic mechanism of DOP might be associated with the regulation of glucagon-mediated hepatic glycogen metabolism and gluconeogenesis, and of liver glycogen structure, contributing to improved hepatic glucose metabolism in diabetic mice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Decolourization of polysaccharides is one of the crucial procedures that affects their structure, which is closely related to their bioactivity. Here, Grifola frondosa polysaccharide (GFP) was decolourized with H2O2 and AB-8 macroporous resin. Then, two main fractions, named DGFP and SGFP, were obtained by purification with Sepharose CL-4B. The molecular weights of these two polysaccharides were determined to be 6.306 × 106 (±0.410%) Da and 1.174 × 107 (±0.299%) Da by HPSEC. Monosaccharide analysis indicated that DGFP was composed of glucose, mannose, and galactose (32.20 : 1.00 : 1.75), while SGFP consisted entirely of glucose. Despite a backbone →4)-α-Glcp-(1→ in two polysaccharides, reducing ends Rα →3)-α-Glcp and Rβ →4)-β-Glcp were observed in DGFP by 1D/2D NMR. The results suggested that decolourization with low concentrations of H2O2 might alter the structure of GFP and generate new reducing ends. In vitro antioxidant results implied that DGFP exhibited a higher ability to scavenge DPPH and hydroxyl radicals and reduced the over-generated ROS levels in a concentration-dependent manner. These results suggested that the antioxidant effects of GFP could be activated by decolourization with H2O2. Therefore, DGFP might be a more promising natural antioxidant than SGFP.

Smilax china L. is a traditional Chinese medicine mainly used for the treatment of pelvic inflammation. Polysaccharide might be one of the anti-inflammatory components of Smilax china L. Based on this hypothesis, this work aimed at extraction, purification and structural elucidation of Smilax china L. polysaccharides and their preliminary anti-inflammatory effects were also studied. Two polysaccharides named SCLP1 (Smilax china L. polysaccharide 1, 42.1kDa) and SCLP3-2 (Smilax china L. polysaccharide 3-2, 16.8kDa) were for the first time purified from Smilax china L. The structures of SCLP1 and SCLP3-2 were elucidated by chemical and spectral analysis. The results revealed that SCLP1 was a neutral polysaccharide composed of glucose and mannose (54.5:1.0). Its backbone was 1,4‑linked α‑Glcp interspersed with 1,2‑linked α‑Glcp and Manp; the branches were 1,6‑linked α-Glcp and terminated with α‑Glcp. SCLP3-2 was composed of galacturonic acid, arabinose, galactose and rhamnose (23.3:2.1:1.7:1.0) and was a pectin-type polysaccharide with an α‑1,4‑linked homogalacturonan backbone which was partially methyl-esterified and slightly acetylated. The side chains consisted of α‑Rhap, β‑Galp and α‑Araf. SCLP1 and SCLP3-2 could inhibit the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells via NF-κB and MAPKs (ERK1/2, JNK) pathways, indicating that they possessed a potential anti-inflammatory activity., (Copyright © 2019 Elsevier B.V. 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.)

Acetaminophen (APAP)-induced hepatic damage is prevalent in western countries. The present study aimed to investigate the hepatoprotective effects of Angelica sinensis polysaccharide (ASP), an active constituent derived from a water extract of Angelica sinensis, in rats exposed to an APAP overdose. The mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters including alanine aminotransferase (ALT), aspartate transaminase (AST), glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) were evaluated, and key proteins involved in hepatic apoptosis, including cleaved caspase-3, Bax and Bcl-2 were quantified. In vivo, H&E staining reveals that ASP reduces the degeneration of hepatocytes and the amount of cytoplasmic vacuolation in rats exposed to an overdose of APAP. ASP markedly alleviated liver injury via an increase in GSH levels and the inhibition of hepatic apoptosis. In vitro, ASP significantly elevated the survival rate of rat primary hepatocytes exposed to an overdose of APAP. The beneficial effect might be, at least in part, due to the amelioration of lipid peroxidation and oxidative stress, along with the inhibition of apoptosis. Taken together, our findings reveal that ASP has potential to be used as a hepatoprotective agent for the management of APAP-induced liver injury., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia. Furthermore, ASP inhibited NF- κ B p65 activation via the I κ B kinases- (IKKs-) I κ B α pathway, thereby reducing the secretion of interleukin-6 (IL-6) and TNF- α , which is known to inhibit erythropoiesis. Our findings indicate that ASP is a potential treatment option for patients suffering from ACD.

Angelica sinensis polysaccharide (ASP), one of the major active ingredients isolated from the roots of Angelica sinensis (Oliv.) Diels, possesses numerous bioactivities. The aim of the present study was to explore the mechanisms of ASP-mediated hypoglycemic effects in type 2 diabetic BALB/c mice induced by multiple low-dose streptozotocin (STZ) injections plus a long-term high-fat diet (HFD) feeding. The potential mechanism explicating the hepatoprotective effect was also considered. Specifically, serum and hepatic biochemical parameters were determined, as well as the key proteins involved in glucose metabolism and apoptosis. The multiple low-dose STZ injection plus HFD treatment induced significant hyperglycemia, hyperlipidemia and marked liver injury. Our results showed that ASP had beneficial effects in preventing hyperglycemia, stimulating insulin secretion, promoting hepatic glycogen synthesis, regulating adipokine release, reducing liver fat accumulation, and attenuating liver injury. Moreover, mechanistic studies illustrated that ASP could upregulate the expression of PPARγ and liver insulin signaling proteins, including IRS-2, PI3K, Akt, p-Akt and GLUT2, increase anti-apoptotic protein Bcl-2, decrease pro-apoptotic protein Bax expressions, and protect the mice against hepatic damage. These findings revealed the potential mechanisms of ASP-mediated therapeutic effects in diabetic mice. It suggested that ASP might be used in prescriptions or functional foods for the prevention or treatment of diabetes and liver diseases.

This study aimed to investigate the therapeutic effects of Angelica sinensis polysaccharide (ASP), an active component derived from a water extract of Angelica sinensis, in high-fat diet (HFD)-fed BALB/c mice. The potential mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters were evaluated, and key proteins involved in the lipid/glucose metabolism were analyzed. Long-term feeding with a HFD induced severe fatty liver and hyperglycemia. Histological examination clearly showed that ASP reduced lipid accumulation in the liver and attenuated hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and liver lipid disorders and fatty liver via the upregulation of PPARγ expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress, demonstrating that ASP might attenuate nonalcoholic fatty liver disease via a "two-hit" mechanism. In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs.

Angelica sinensis polysaccharide (ASP), extracted from the roots of A. sinensis (Oliv.) Diels, is a β-D-pyranoid polysaccharide with an average molecular weight of 72,900 Da. In this study, we investigated the protective effects of ASP against concanavalin A-induced liver failure and the underlying mechanisms. Concentrations of ASP ranging from 5 to 125 μg/mL could inhibit concanavalin A (ConA)-induced lymphoproliferative response. The potential hepatoprotective activity of ASP was demonstrated by the significant decrease in serum transaminase (ALT and AST) levels and the attenuation of liver inflammation damage exhibited by H&E stain of the liver. Furthermore, ASP pretreatment significantly decreased proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-6) and alleviated oxidative stress by reducing MDA and ROS levels and by enhancing SOD activity after ConA administration in mice. Results of Western blot analysis indicated that ASP attenuated Caspase-3-dependent apoptosis by Caspase-8 and JNK-mediated pathway and inhibited the activation of IL-6/STAT3 and NF-κB signaling pathways in ConA-induced liver damage in mice. In conclusion, ASP pretreatment could attenuate concanavalin A-induced liver injury through its anti-inflammatory and anti-oxidant actions in mice., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The crude polysaccharide was obtained from the root of Angelica sinensis (AS) to investigate its effect on tumor growth and iron metabolism in H22-bearing mice. In our study, we showed that Angelica sinensis polysaccharide (ASP) was mainly composed of arabinose, glucose and galactose in a molar ratio of 1:1:1.75, with a molecular weight of 80,900 Da and a sugar content of 88.0%. Animal experimental results revealed that three doses of ASP all had anti-tumor effects with inhibition ratios of 27.11%, 31.65% and 37.05%. With respect to iron metabolism, the mean levels of serum hepcidin, interleukin-6 (IL-6), ferritin, transferrin (Tf), transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2) in H22-bearing mice were promoted, and serum iron concentration decreased significantly. After treatment with ASP, these iron-related indicators recovered in different degrees. The findings suggested that the anti-tumor activity of ASP may be affected by its regulation on iron metabolism in H22-bearing mice.

The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-α in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes.

A crude polysaccharide was obtained by water extraction and ethanol precipitation from the root of Angelica sinensis (AS) to investigate its suppressive effect on hepcidin expression in rats with iron deficiency anemia (IDA). In this study, we showed that the Angelica sinensis polysaccharide (ASP) was mainly composed of arabinose, glucose and galactose in a molar ratio of 1 : 2.5 : 7.5, with the molecular weight of 72 900 Da and the sugar content of 95.1%. ASP markedly decreased hepcidin expression by suppressing the expression of JAK1/2, phospho-JAK1/2, phospho-SMAD1/5/8, phospho-ERK1/2, and promoting the expression of SMAD7 in the liver. These findings suggest that ASP can prevent the janus-kinase (JAK), son of mother against decapentaplegic (SMAD) and extracellular signal-regulated kinase (ERK) pathways to down-regulate hepcidin expression in IDA rats, and may be useful for the treatments of diseases induced by hepcidin over-expression.

This study compared a new type of polysaccharide-coated magnetic nanoparticles (in which the polysaccharide is derived from Angelica sinensis) with the dextran magnetic nanoparticles in terms of preparation, biocompatibility and tissue distribution in vivo and in vitro in order to examine the potential application of Angelica polysaccharide as a novel carrier in magnetic drug targeting (MDT). Magnetic nanoparticles were prepared by chemical co-precipitation. Their physical and chemical properties were determined by using the transmission electron microscope (TEM), laser particle size analyzer (DLS) and vibrating sample magnetometer (VSM), and their purity and structure by using X-ray diffractometer (XRD) and Fourier transform infrared spectroscopy (FTIR). The atomic absorption spectrometric method was performed for quantification of the iron content in different tissues. Histological sections were stained by Prussian blue staining to observe the disposition of magnetic nanoparticles in the liver and kidney. The results showed that both kinds of magnetic nanoparticles possessed small particle size, good dispersion and good magnetic properties. XRD showed the main component of the two magnetic nanoparticles was Fe(3)O(4) crystals, and FTIR proved Fe(3)O(4) was successfully coated by each polysaccharide, respectively. In vivo, Fe(3)O(4)-dextran accumulated in the liver, spleen and lung and Fe(3)O(4)-Angelica polysaccharide only in the spleen and lung. It was concluded that Angelica polysaccharide may be applied as a novel carrier in the preparation of magnetic nanoparticles.

Context: Polysaccharide purified Lentinus edodes (Berk.) Sing (Tricholomataceae) has been reported to attenuate oxidative stress in vitro., Objective: This study investigated whether polysaccharides from L. edodes with different molecular weight have protective effects against oxidative stress induced by D-galactose (D-gal) in vivo, and determined the specific relationship between molecular weight and antioxidant activity., Materials and Methods: In the present study, we successfully obtained three purified polysaccharides, coded as LT1, LT2, and LT3, and their molecular weights were 25.5, 306.2, and 605.4 kDa, respectively. The D-gal-treated mice received three polysaccharides once daily for 60 days. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of malondialdehyde (MDA), and erythrocyte membrane fluidity were measured to evaluate the changes of the antioxidant ability., Results: It was demonstrated that the administration of LT1, LT2, and LT3 could improve the antioxidant status to different levels. Furthermore, LT2 exhibited the highest antioxidant ability among these samples in vivo. Indeed, LT2 significantly decreased the content of MDA in liver (15.91 ± 0.31 versus 23.79 ± 1.18 nmol/mg protein for the model group, p < 0.05), enhanced the fluidity of erythrocyte membrane (2.458 ± 0.023 versus 2.167 ± 0.024 for the model group, p < 0.05), and increased the activities of SOD (147.19 ± 4.90 versus 82.26 ± 5.55 units/mg protein for the model group, p < 0.05) and GSH-Px (310.91 ± 6.24 versus 243.64 ± 6.77 units/mg protein for the model group, p < 0.05) in liver., Discussion and Conclusion: The LT2 had a potential to be used as a novel natural antioxidant.

Dendrobium catenatum Lindl. has been long used in China as a functional food and traditional Chinese medicine and polysaccharides from Dendrobium catenatum Lindl. (DOP) exhibited extensive bioactivities. However, studies on the structure-activity relationship of DOP are rarely reported. Here, two polysaccharides named DOP-1 and DOP-2 were obtained, which differed in the ratio of monosaccharide composition and molecular weight. Structural characteristics were elucidated by spectral and chemical analysis. The main structures of DOPs were the linkage of β-(1→4)-D-Manp, with some attached 2-O- or 3-O-acetylated groups. Additionally, the DPPH, hydroxyl and superoxide radicals scavenging assays of DOP-1 and DOP-2 showed that DOP-2 exhibited the higher antioxidant activity, which might be related to its lower molecular weight, higher mannose proportion and lower degree of acetylation, and higher phenolic content. Our results provide a more accurate basis for the application of DOPs in the pharmaceutical and food industries. [ABSTRACT FROM AUTHOR]

The alleviation of oxidative stress is considered an effective treatment for acetaminophen (APAP)-induced acute liver injury (AILI). However, it remains unknow whether the potential antioxidant Smilax china L. polysaccharide (SCLP) protects against AILI. In this study, in vitro and in vivo experiments were conducted to verify the hepatoprotective effect of SCLP against AILI and explore the potential mechanism. We found that SCLP relieved liver histopathological changes; reversed the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and reactive oxygen species (ROS); reversed the change in liver myeloperoxidase (MPO) activity; and enhanced liver antioxidant (GSH, GSH-Px, and t-SOD) levels in APAP-treated mice, thereby significantly reducing APAP-induced liver toxicity. SCLP rescued the cell viability and alleviated oxidative stress in H2O2-treated mouse AML12 (Alpha mouse liver 12) hepatocytes. The results of the mechanistic studies showed that SCLP upregulated nuclear factor E2 related factor (Nrf2) expression, promoted Nrf2 nuclear translocation, and enhanced the ability of Nrf2 to bind antioxidant response elements (AREs). Furthermore, SCLP activated Nrf2-ARE pathway, thus upregulating the expression of oxidative stress-related proteins heme oxygenase 1(HO-1), NAD(P)H quinone dehydrogenase 1(NQO-1) and glutamic acid cysteine ligase catalytic subunit (GCLC). In conclusion, this study confirmed the close correlation between liver protection by SCLP upon exposure to APAP and activated of the Nrf2-ARE pathway. These findings suggest that SCLP is an attractive therapeutic candidate drug for the treatment of AILI. [ABSTRACT FROM AUTHOR]

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-Gal p occasionally substituted by α-Ara f at O-2 and/or O-3. AG-II was a highly branched polysaccharide with long branches of α-Ara f , which were attached to the O-3 of 1,6-linked β-Gal p 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. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, a porous sponge material was formed by physically mixing chitosan (CS) and Angelica sinensis polysaccharide (ASP). After removing the water by freeze-drying, the CS/ASP sponge was obtained. The prepared sponges exhibited excellent swelling properties, thermal stability and biocompatibility as well as improvements over the insufficient mechanical properties of pure chitosan sponges. Notably, the ASP released from the CS/ASP sponge could be effectively absorbed by the liver, which endowed the CS/ASP sponge with effective liver-protective effects against CCl 4 -induced acute liver injury; these protective effects surpassed those of both blank CS and CS/Dextran sponges. The underlying protective mechanism may involve the activation of the Nrf2-mediated antioxidant signaling pathway and the inhibition of hepatocyte apoptosis. Understanding CS/ASP sponges may provide new insights and inspire new methods for the clinical application of ASP. At the same time, we hope to suggest future directions for the development of polysaccharide preparations. • Chitosan (CS)/ Angelica sinensis polysaccharide (ASP) sponges were prepared. • ASP released from the sponges could be absorbed efficiently by the liver. • The sponges showed liver-protective effects against CCl 4 -induced acute liver injury. [ABSTRACT FROM AUTHOR]

As typical acetylated glucomannans, Dendrobium officinale polysaccharides (DOPs) from different origins differ in their structural characteristics and some of their physicochemical properties. To rapidly select D. officinale plants, we systematically investigate the differences among DOPs from different origins and analyzed the structural characteristics, such as the degree of acetylation and monosaccharide composition; the physicochemical properties, such as solubility, water absorption and apparent viscosity; and the lipid-lowering activity of the obtained DOPs. Principal component analysis (PCA), a method for analyzing multiple variables, was used to analyze the relationship between the physicochemical and structural properties, and lipid-lowering activity. It was found that the structural and physicochemical characteristics had significant effects on lipid-lowering activity, and DOPs with a high degree of acetylation, high apparent viscosity and large D-mannose-to- d -glucose ratio were associated with greater lipid-lowering activity. Therefore, this study provides a reference for the selection and application of D. officinale. [ABSTRACT FROM AUTHOR]

Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of Angelica sinensis polysaccharide (ASP) and its underlying mechanism in the treatment of renal anemia. In the present study, we found that ASP could enhance hypoxic induction of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF-2α protein. In parallel, ASP rescued the inhibition of EPO, induced by proinflammatory factor TNF-α through blocking GATA2 and NF-κB activation. In a rat model of adenine-induced anemia of CKD, oral administration of ASP corrected anemia and alleviated renal damage and inflammation. By increasing the accumulation of HIF-2α protein and reducing the expression of NF-κB and GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and hepatic EPO production, and resulted in an elevation of serum EPO. The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and increased serum iron. These findings demonstrate that ASP elicits anti-anemic action by restoring EPO production and improving iron availability in the setting of CKD in rats. [ABSTRACT FROM AUTHOR]

To investigate the absorption and delivery of ASP in gastrointestinal (GI) tract, cASP was successfully synthesized by chemically modifying with succinic anhydride and then conjugating with a near infrared fluorescent dye Cy5.5. Then, the capacity of oral absorption of cASP was evaluated. The results demonstrated that cASP had low toxicity and no disruption on the integrity of cell membrane. The endocytosis of cASP into the epithelial cells was time- and energy-dependent, which was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes. Otherwise, the actin filaments played a relatively weak role at the same time. The transport study illustrated that cASP could penetrate through the epithelial monolayer and mainly mediated by the same routes as that in the endocytosis experiment. Moreover, bothin vitroUssing chamber andin vivoligated intestinal loops models indicated that cASP could be diffused through the mucus barriers and be absorbed in the whole small intestine. Finally, near-infrared fluorescence imaging presented that cASP could be absorbed and circulated into the blood, then distributed into various organs after oral administration. In conclusion, ASP could be absorbed after oral administration through endocytosis process mainly mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes, then be absorbed and circulated into blood. This study presents a comprehensive understanding of oral delivery of cASP, which will provide theoretical basis for the clinical application of ASP. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sulfated Grifola frondosa polysaccharide was prepared and characterized. • Sulfation and degradation could exist concurrently during the sulfation reaction. • S-GFP is a noncompetitive inhibitor of α-glucosidase. • S-GFP could significantly quench the endogenous fluorescence of α-glucosidase. Sufalted modification of Grifola frondosa polysaccharide (GFP) was performed using the chlorosulfonic acid-pyridine (CSA-Pyr) method. The chemical structure and α-glucosidase inhibitory activity of sulfated Grifola frondosa polysaccharide (S-GFP) were investigated. FT-IR and NMR spectra both revealed C-6 as the main substituted position owing to steric hindrance. Molecular weight (Mw) analysis indicated that sulfation and degradation could exist concurrently during the sulfation reaction given that the Mw of S-GFP was different from that of natural GFP. Inhibition test of α-glucosidase activity implied that S-GFP is a noncompetitive inhibitor of α-glucosidase. S-GFP effectively inhibited the activity of α-glucosidase with an IC 50 value of 3.353 µg mL−1. The results of inhibitory mechanism indicated that S-GFP quenched the endogenous fluorescence of α-glucosidase and changed the backbone structure of the protein. Circular dichroism (CD) analysis showed that treatment with S-GFP changed the conformation of α-glucosidase, increased the content of the α-helix structure, and destroyed the hydrogen bond system of the enzyme. This experiment aims to elucidate the potential α-glucosidase inhibitory activity of sulfated polysaccharides and to provide new insights into the targets of their bioactivities. [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

Angelica sinensis polysaccharide (ASP) has presented increasingly recognized lipid regulation and antioxidant abilities. However, there is little direct evidence to explain why ASP possesses the observed lipid-lowering and anti-oxidation effects. In vivo and in vitro models of alcoholic fatty liver disease (AFLD) were established to examine the direct effect of ASP on hepatic fat accumulation. Our results showed that the lipid-lowering effect of ASP might result from the dual inhibition of lipid synthesis and CD36-mediated lipid uptake. The antioxidation of ASP might be attributed to the reversal of alcohol metabolic pathways from CYP2E1 catalysis to ADH catalysis. Taken together, the study demonstrated the direct role of ASP in lipid metabolism for the first time and revealed the underlying mechanism of reducing ROS, providing an available strategy for ASP as a potential agent to treat AFLD. [Display omitted] • The improvement effect of ASP on AFLD was confirmed for the first time. • ASP could reduce the hepatic levels of ACC and FAS to suppress lipid synthesis. • ASP could return hepatic CD36 content to normal levels to inhibit lipid uptake. • ASP could promote alcohol metabolism by enhancing ADH pathway in AFLD mice. [ABSTRACT FROM AUTHOR]

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. [Display omitted] [ABSTRACT FROM AUTHOR]

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with deleterious maternal and fetal outcomes. Angelica sinensis polysaccharide (ASP) has been shown to reduce hepcidin expression in IDA rats. However, the role of ASP in the treatment of IDA during pregnancy and its potential mechanisms have not been investigated. Moreover, the effect of ASP on duodenal iron absorption is not clear. The aim of this study was to investigate the preventive efficacy of ASP against IDA during pregnancy and clarify the underlying mechanisms. Our results showed that ASP improved maternal hematological parameters, increased serum iron, maternal tissue iron, and fetal liver iron content, and improved pregnancy outcomes. Additionally, ASP combated oxidative stress caused by iron deficiency by improving the body's antioxidant capacity. Western blot results demonstrated that ASP downregulated hepcidin expression by blocking the BMP6/SMAD4, JAK2/STAT3 and TfR2/HFE signaling pathways, which in turn increased the expression of FPN1 in the liver, spleen, and duodenum and promoted iron cycling in the body. Furthermore, ASP increased the expression of DMT1 and Dcytb in the duodenum, thereby facilitating duodenal iron uptake. Our results suggest that ASP is a potential agent for the prevention and treatment of IDA during pregnancy. [Display omitted] • ASP improved anemia symptoms and adverse pregnancy outcomes in IDA pregnant rats. • ASP regulated iron homeostasis in IDA pregnant rats via the hepcidin-FPN1 axis. • ASP enhanced the absorption of dietary iron by increasing DMT1 and Dcytb levels. • ASP facilitated iron recycling in senescent erythrocytes by increasing HO-1 levels. [ABSTRACT FROM AUTHOR]

Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • A novel capsule polysaccharide (CPS-605) is obtained from Lactobacillus plantarum LCC-605. • AM is successfully conjugated with CPS-605 to generate CPS-AM NPs. • CPS-AM NPs significantly reduce the working concentration of amikacin. • CPS-AM NPs exhibit excellent antibacterial activity against Gram-negative strains. • CPS-AM NPs show great biofilm inhibition and disruption abilities. [ABSTRACT FROM AUTHOR]

Despite the great progress in the treatment of hepatocellular carcinoma, combination chemotherapy is still the main choice of treatment for patients with unresectable metastatic or recurrent hepatocellular cancer. Lentinan, which has been used as an immunomodulator in the treatment of cancer, possesses anti-tumor activities. However, the mechanisms by which Lentinan inhibits hepatocellular carcinoma remain unknown. Our study showed that Lentinan has a significantly synergistic anti-tumor effect with oxaliplatin against HepG2 cells in vitro and in H22 tumor-bearing mice through the mitochondria pathway and for the inhibition of NF-κB, Stat3 and survivin signaling. Moreover, Lentinan moderated side effects induced by oxaliplatin. These findings suggested that Lentinan may be an ideal agent for the combination therapy of oxaliplatin against hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Highlights: [•] A water-soluble hyper-branched α-glucan RPS3 was firstly derivatized. [•] SEC-MALLS-Vis-RI combination instrument was used to characterize the polysaccharides. [•] The derivatives exhibited more extended chain conformation than the native RPS3. [•] α-Glucan RPS3 could show anti-tumor activity after derivatization. [ABSTRACT FROM AUTHOR]