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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 × 107 vs. 2.13 ± 0.52 × 107) and butyrate (1.83 ± 1.31 × 107 vs. 6.39 ± 1.44 × 107). 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. [ABSTRACT FROM AUTHOR]

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. Unlabelled Image [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]

Graphical abstract Highlights • ASP administration could improve the hyperglycemia and hyperlipoidemia. • ASP protects pancreatic islets against high-fat diet and streptozotocin-induced injury. • ASP inhibits the apoptosis of β-cells by regulating extrinsic and intrinsic pathways. • ASP increases the insulin levels and promotes the insulin secretion. Abstract Type 2 diabetes mellitus (T2DM) is becoming an expanding global health concern, closely linked to the islet dysfunction. This study aimed to investigate the protective effects of Angelica sinensis polysaccharide (ASP), derived from the roots of Angelica sinensis (Oliv.) Diels, on pancreatic islets of T2DM mice. Our research showed that ASP could ameliorate hyperglycemia, restore lipid profile changes and protect against liver injury. ASP increased the Bcl-2/Bax ratio to block caspase-9-caspase-3 cascade in islet β-cells. Simultaneously, the suppression of a caspase-8-driven extrinsic apoptotic pathway further inhibited the activation of subsequent substrate proteins, such as PARP. Results of immunohistochemistry and immunocytochemistry indicated that ASP could increase cell insulin stores. Additionally, ASP could promote the secretion of insulin to attenuate the glucotoxicity by stimulating the insulin gene expression. Taken together, this study suggested that ASP might be applied as a functional food or additive to treat diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [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]

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-1β, 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. [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]

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. [ABSTRACT FROM AUTHOR]