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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.)

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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2023. Published by Elsevier B.V.)

Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 10 7 vs. 2.13 ± 0.52 × 10 7 ) and butyrate (1.83 ± 1.31 × 10 7 vs. 6.39 ± 1.44 × 10 7 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine-choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD., (© 2023 John Wiley & Sons Ltd.)

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., (Copyright © 2022. Published by Elsevier B.V.)

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.)

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.)

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.

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]