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Background: Pyroptosis, a form of inflammatory programmed cell death, has recently emerged as a pivotal factor in the pathogenesis of myocardial ischemia/reperfusion (MI/R) injury. Despite its significance, effective therapeutic strategies targeting MI/R-induced pyroptosis remain elusive in current clinical practice. Previous studies have demonstrated the promising anti-inflammatory effects of Angelica sinensis polysaccharide (ASP) in the context of certain inflammatory disorders. Objectives: We aimed to investigate the effects of ASP on pyroptosis in MI/R injury and elucidate the potential molecular mechanisms by combining transcriptomic analysis with complementary in vivo and in vitro experiments. Materials and methods: H9c2 cells were used to establish a hypoxia/reoxygenation (H/R) model, and MI/R injury was induced in rats by ligating and releasing the left anterior coronary artery. Myocardial tissue samples were harvested for transcriptomic sequencing and bioinformatic analyses. Cardioprotective effects were evaluated through electrocardiography, echocardiography, and histological examination. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify levels of inflammatory mediators. Biochemical assays were conducted to assess myocardial injury biomarkers and Caspase-1 activity. Western blotting was performed to analyze the protein expression levels of Fibronectin 1 (FN1), Nuclear factor kappa B (NF-κB) p65, phosphorylated NF-κB p65 (p-NF-κB p65), Nod-like receptor protein 3 (NLRP3), and Gasdermin-D (GSDMD). Results: Pretreatment with ASP conferred potent cardioprotective effects in a rat model of MI/R injury, as evidenced by significant attenuation of infarct size, myocardial enzyme levels, and ST-segment elevation on electrocardiography, alongside notable improvements in cardiac function. Transcriptomic profiling unveiled that differentially expressed genes modulated by ASP treatment were predominantly implicated in the pyroptosis-elicited inflammatory response. Concordantly, both in vivo and in vitro experiments substantiated that ASP treatment effectively attenuated MI/R-induced pyroptosis, as manifested by diminished levels of pyroptosis-related indicators, encompassing the proportion of TUNEL-positive cells, Caspase-1 activation, GSDMD cleavage, and the liberation of pro-inflammatory cytokines. Further mechanistic investigations revealed ASP inhibition of the FN1/NF-κB/NLRP3 signaling pathway. Conclusions: Our investigation, leveraging system-level transcriptomic profiling, demonstrates that ASP confers cardioprotective effects against MI/R injury through the suppression of cardiomyocyte pyroptosis, culminating from downregulation of the FN1/NF-κB/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: How to improve the hematopoietic microenvironment is a hot topic in the treatment of aplastic anemia. OBJECTIVE: To explore the action mechanism of Angelica sinensis polysaccharide in the treatment of aplastic anemia by combining GEO sequencing analysis, network pharmacology, and experimental validation. METHODS: Aplastic anemia-related differentially expressed genes were obtained from GEO database, and gene ontology and gene set enrichment analysis were performed. The active components and targets of Angelica sinensis polysaccharide were obtained by combining the literature with PubChem, SwissTargetPrediction, and PharmMapper databases. After the intersection targets were taken, STRING and Cytoscape were used to construct proteinprotein interaction network, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed. Mouse model of aplastic anemia was established, and the effect and action mechanism of Angelica sinensis polysaccharide on aplastic anemia were verified by blood cell analyzer, flow cytometry, ELISA, immunohistochemistry, immunofluorescence, and western blot assay. RESULTS AND CONCLUSION: (1) A total of 834 differentially expressed genes were screened, which were involved in biological processes such as cell development, hematopoiesis, and myeloid cell differentiation. (2) 347 targets related to Angelica sinensis polysaccharide were retrieved and 77 potential therapeutic genes were screened. Among them, the degree values of angiogenic, apoptotic, and immune-related factors such as VEGFA, EGLN1, Bcl-2, interferon-γ, interleukin-2, interleukin-4, and interleukin-6 were significant. (3) KEGG pathway enrichment analysis revealed that the therapeutic targets were mainly enriched in Th17 cell differentiation, NK-related cytotoxicity, cell adhesion factors such as interferon-γ, interleukin-2, and interleukin-4 related signaling pathways. (4) Animal experiments showed that Angelica sinensis polysaccharide significantly improved bone marrow haematopoiesis, increased peripheral blood cell, and bone marrow single nucleated cell counts, and improved the survival rate of mice. Compared with the model group, mice in the Angelica sinensis polysaccharide group showed a significant decrease in the ratio of Th1/Th2 cells (P < 0.01), a decrease in the expression level of interferon-γ (P < 0.01), an increase in the level of interleukin-4 (P < 0.05), a significant increase in the level of VEGFA (P < 0.01), a significant decrease in EGLN1 (P < 0.01), a significant decrease in apoptosis rate of bone marrow single nucleated cells and reactive oxygen species level (P < 0.01), and a significant increase in cleaved Caspase-3 protein expression (P < 0.01), and a significant decrease in Bcl-2/Bax ratio (P < 0.01). (5) These findings show that Angelica sinensis polysaccharide can improve hematopoiesis of aplastic anemia mice by regulating aberrant T-cell subsets and promoting angiogenesis to improve hematopoietic microenvironment, and inhibiting apoptosis of bone marrow mononuclear cells. [ABSTRACT FROM AUTHOR]

In the present study, the effect of ionization modification on the morphology and in vitro antioxidant activity of Angelica Sinensis polysaccharide (ASP) was researched. ASP was used as raw material to obtain phosphorylated Angelica Sinensis polysaccharide (ASP-P) and cationized Angelica Sinensis polysaccharide (ASP-N). The degree of phosphorylation and cationization of ASP were determined by experiments. Structural characterization and thermal stability testing of ionized ASP derivatives were explored by infrared spectroscopy, thermogravimetric analysis, X-red diffraction, dynamic light scattering, Congo-red test and scanning electron microscopy. The ionization modified ASP have better thermal stability, among which ASP-P has the best thermal stability. ASP-P and ASP-N showed more ordered structure in solid state and the ionized ASP-P and ASP-N in solution all maintain the triple helix architecture of ASP, but exhibited a larger size of stacked or curled sheet morphology in solidity. The scavenging assays of hydroxyl radical, ABTS and DPPH radical were used to evaluate the changes in the antioxidant capacity of ASP before and after ionization modification. The ionic modification products of ASP can significantly improve the scavenging ability in vitro. The above experimental results provide an experimental basis for further research on the derivatization of ASP. [ABSTRACT FROM AUTHOR]

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator‐activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT‐PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end‐labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA. [ABSTRACT FROM AUTHOR]

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]

Objective To establish in vivo and in vitro models of myocardial ischemia-reperfusion injury(MIRI ) in rats, to observe the improvement effect of Angelica polysaccharide(ASP ) on MIRI rats and to explore its mechanism. Methods In vivo study, adult SD rats were randomly divided into the sham group, MIRI group, low-dose ASP group and high-dose ASP group. Except the sham group, the MIRI models were established by ligation and reperfusion of the left anterior descending branch of coronary artery in the other groups. After modeling, the rats in the low-dose and high-dose ASP groups were given 50 and 100 mg/kg ASP by intragastric administration, once a day, for 4 weeks, respectively. Rats in the sham group and MIRI group were given the equal volume of normal saline. Serum markers of myocardial injury such as creatine kinase-MB(CK-MB ), lactate dehydrogenase(LDH ), tumor necrosis factor-α(TNF-α ), interleukin6(IL-6 ), and IL-1β were detected by ELISA. The expression levels of apoptotic proteins Bax, Bcl-2, cleaved Caspase-3, and TLR4/NF-κB pathway-related proteins TLR4, p-p65, and p-IκBα were detected by Western blotting. In vitro study, H/R cardiomycetes(derived from neonatal cell culture ) were divided into the control group, hypoxia reoxygenation(H/R ) group, low-dose H/R+ASP group and high-dose H/R+ASP group. The control group was cultured normally without treatment, and in vitro cardiomyocyte H/R models were established in the other three groups. After modeling, the low-dose and high-dose H/R+ASP groups were added with 5 and 10 µg/mL ASP, respectively, and the H/R group was not treated. MTT colorimetric assay was used to detect cardiomyocyte activity, and ELISA was used to detect inflammatory cytokines TNF- α, IL-6 and IL-1β. Western blotting was used to detect apoptotic proteins Bax, Bcl-2, cleaved Caspase-3, and TLR4/NFκB pathway proteins TLR4, p-p65, and p-IκBα in each group. Results In vivo, the levels of serum myocardial injury markers(LDH and CK-MB ) and serum inflammatory factors(TNF-α, IL-6 and IL-1β ) ranked from high to low: MIRI group, low-dose ASP group, high-dose ASP group, and sham group(all P<0. 05 ). Myocardial Bax and cleaved Caspase-3 protein expression ranked from high to low: MIRI group, low-dose ASP group, high-dose ASP group, sham group, and myocardial Bcl-2 protein expression ranked from high to low: sham group, high-dose ASP group, low-dose ASP group, MIRI group(all P<0. 05 ). The expression levels of TLR4/NF-κB pathway-related proteins TLR4, P-P65 and P-iκBα in the myocardial tissues were higher in the MIRI group than in the low-dose ASP group, which were higher than those of the high-dose ASP group, followed by the sham operation group(all P<0. 05 ). In vitro study, cardiomyocyte activity ranked from high to low: control group, high-dose H/R+ASP group, low-dose H/R+ASP group, and H/R group(all P<0. 05 ); the levels of cytokines TNF-α, IL-6 and IL-1β in H/R group were higher than those in H/R+ASP low-dose group, which were higher than those in the high-dose H/R+ASP group, followed by the control group(all P<0. 05 ). Bax and cleaved caspase-3 protein expression ranked from high to low： H/R group, low-dose H/R+ASP group, high-dose H/R+ASP group, and control group. Cardiac Bcl-2 protein expression ranked from high to low： control group, high-dose H/R+ASP group, low-dose H/R+ASP group, and H/R group(all P<0. 05 )； the expression levels of TLR4/NF-κB pathway-related proteins(TLR4, P-P65 and P-iκbα in cardiomyoma cells ) in the H/R group were higher than those in the low-dose H/R+ ASP, which were higher than those of the high-dose H/R+ASP group, and those were higher in the high-dose H/R+ASP group than the control group(all P<0. 05 ). Conclusion ASP can improve MIRI in both in vivo and in vitro ischemia-reperfusion models, and its mechanism may be related to inhibiting the activation of TLR4/NFκB pathway, alleviating inflammation, and reducing apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the ameliorative effect of Angelica sinensis polysaccharide (ASP) in myocardial ischemia-reperfusion injury (MIRI) rats through Toll-like receptor 4 (TLR4)/Nuclear factor κB (NF-κB) pathway. Methods: The MIRI rat model was established. Sprague-Dawley rats were randomized to sham, MIRI, and ASP low-dose (50 mg/kg) and high-dose (100 mg/kg) groups, and a model of hypoxiareoxygenation (H/R) injury was established. In in vitro studies, H/R cardiomycetes (derived from neonatal cell culture) were randomized to control, H/R, H/R + ASP low dose (5 μg/mL), H/R + ASP high dose (10 μg/mL), and ASP high dose + TLR4 activator groups. Results: After intragastric administration of ASP for 4 consecutive weeks, creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were reduced after ASP treatment in MIRI rats (p < 0.05). Both in vivo and in vitro, ASP reduced TNF-α, IL-6, and IL-1β expressions (p < 0.05), and alleviated inflammatory response. Apoptosis was inhibited by ASP, which also increased Bcl2, reduced Bax and cleaved caspase-3 expressions, while TLR-4, p-IκBα, and p-p65 were decreased. Conclusion: The cardioprotective effect of ASP on MIRI results in the inhibition of TLR4/NF-κB pathway. Thus, this study broadens the current body of knowledge on the pharmacological prevention of MIRI and the therapeutic potential of ASP. [ABSTRACT FROM AUTHOR]

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors.

Objective To investigate the effect and mechanism of Angelica sinensis polysaccharides (ASP) on the hematopoietic reconstitution of recipient mice after bone marrow transplantation. Methods Bone marrow cells were derived from 10 male C57BL/6J mice (20~25 g), and 30 female recipient mice (8~10 weeks old) were irradiated with 8.0 Gy lethal dose of X-ray. The bone marrow cells from donor mice were infused through tail vein to construct the mouse bone marrow transplantation model. The recipient mice were randomly divided into 3 groups with 10 mice in each group: control group (Ctrl): no bone marrow cells were transplanted in recipient mice; Bone marrow transplantation group (BMT): recipient mice were transplanted with bone marrow cells of donor mice (5×106/each); Bone marrow transplantation+Angelica sinensis polysaccharide group(TASP): radiation dose and the numbers of transplanted bone marrow cells were the same as those of BMT group. At the same time, the recipient mice were given the ASP by intraperitoneal injection (100 mg/kg×9 d). The change in body weight of recipient mice was measured dynamically. In the ninth day after bone marrow cells transplantation, Y chromosome genes in colony-forming cells in spleen and bone marrow cells of recipient mice were detected by PCR. Blood samples were collected from the orbit of the recipient mice to measure the number of WBC, RBC and PLT and the level of HGB. Femurs were taken after the recipient mice were killed, and the number of bone marrow nucleated cells (BMNC) in each femur was counted. The bone marrow cell cycle was detected by flow cytometry. Bone marrow stromal cells (BMSCs) were cultured in vitro. The adherent status of BMSCs was observed, cell proliferative capacity was detected by EDU, and colony forming unit-fibroblastic (CFU-F) numbers were counted. The contents of hematopoietic factors in serum and supernatant of BMSCs were determined by ELISA. Results All mice in the control group died within 7 d, and all animals in the other groups survived. The body weight of mice in the BMT and TASP groups decreased to the lowest level and began to recover after 5~6 d, and the TASP group showed a faster recovery in body weight (P < 0.05). Y chromosome genes were detected in colony-forming cells in spleen and bone marrow cells of recipient mice. The number of WBC, RBC and the level of HGB in the TASP group were increased compared with the BMT group (P < 0.01; P < 0.05). The number of BMNCs in each femur in the TASP group were significantly higher than those in the BMT group (P < 0.05). In the TASP group, the cell proportion decreased in the G0/G1 phase, and the cell proportion in the S and G2/M phase increased compared with the BMT group(P < 0.05); The adherent numbers of BMSCs, proliferation ability and CFU-F numbers in the TASP mice were also significantly higher than those in the BMT group (P < 0.05). The contents of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3) in serum and GM-CSF and stem cell factor (SCF) in supernatant of BMSCs were increased in the TASP group compared with the BMT group (P < 0.05). Conclusion ASP can promote hematopoietic reconstitution in recipient mice after bone marrow cells transplantation of donor mice, and the preliminary mechanism may be related to improving hematopoietic microenvironment and promoting secretion of hematopoietic factors.

Background: Extrinsic molecular mechanisms that regulate hematopoietic stem/progenitor cell (HSPC) aging are still poorly understood, and a potential protective medication needs to be explored. Materials and methods: The senescent parameters of hematopoietic cells and bone marrow stromal cells (BMSCs) including cell cycle analysis, senescence-associated SA-β-gal staining and signals, hematopoietic factors and cellular junction were analyzed in femur and tibia of rats. Furthermore, Sca-1+ HSPCs and BMSCs co-culture system was established to evaluate the direct effects of BMSC feeder layer to HSPCs. Oxidative DNA damage indicators in Sca-1+ HSCs and senescence-associated secretory phenotype (SASP) of BMSCs, gap junction intercellular communication between BMSCs, osteogenesis/adipogenisis differentiation balance of BMSCs were detected. Results: In the D-gal pre-administrated rats, ASP treatment rescued senescence of hematopoietic cells and BMSCs, reserved CFU-GEMM; also, ASP treatment attenuated stromal oxidative load, ameliorated SCF, CXCL12, and GM-CSF production, increased Connexin-43 (Cx43) expression. BMSCs and Sca-1+ HSPCs co-cultivation demonstrated that ASP treatment prevented oxidative DNA damage response in co-cultured Sca-1+ HSPCs induced by D-gal pre-administration of feeder layer and the underlying mechanism may be related to ASP ameliorating feeder layer dysfunction due to D-gal induced senescence via inhibiting secretion of IL-1, IL-6, TNF-α, and RANTES, enhancing Cx43-mediated intercellular communication, improving Runx2 expression whereas decreasing PPARγ expression in BMSCs. Conclusion: The antioxidant property of ASP may provide a stroma-mediated potential therapeutic strategy for HSPC aging. [ABSTRACT FROM AUTHOR]

Inappropriate treatment of chronic inflammation and infection can lead to serious consequences, with anemia being the most common secondary disease that often requires systematic treatment. However, the complex pathology and gastrointestinal irritation associated with oral iron supplements limit their effectiveness. To address this, a bioactive ingredient derived from natural herbs, Angelica sinensis polysaccharide (ASP), was utilized as an ideal adjuvant for regulating the size and stability of iron oxide nanoparticles (IONPs). Highly hydrophilic ASP-modified IONPs (IONPs@ASP) with a mesoporous structure were developed under the induction of microemulsion.The as-prepared IONPs@ASP exhibited enhanced stability, retention performance and controlled degradation in blood and lysosomal environments, respectively, which is beneficial for long-term intravenous iron maintenance in anemia treatment. After confirming the biosafety of IONPs@ASP, pharmacodynamic results showed that hemoglobin levels increased significantly and rapidly returned to normal levels in anemia model rats treated with IONPs@ASP, even surpassing the effects of IONPs or ASP monotherapy. Additionally, analysis of inflammatory factors in rat serum suggested that ASP effectively upregulated the expression of anti-inflammatory factors, indicating synergistic effects of iron-based nanomedicine and immune regulation in anemia treatment. These findings represent a significant advancement in anemia treatment and open new possibilities for developing versatile nanoparticles based on ASP. • ASP significantly enhances the stability and hydrophilicity of IONPs. • ASP improve the retention performance of IONPs in the bloodstream. • ASP involvement effectively prevents IONPs from crossing biological barriers. • ASP could enhance the synergistic anti-anemia effect of nanodrugs. • It opens new avenues for expanding the application of ASP in biomedicine. [ABSTRACT FROM AUTHOR]

Currently, the polluted wastewater discharged by industry accounts for the major part of polluted bodies of water. As one of the industrial wastewaters, dye wastewater is characterized by high toxicity, wide pollution, and difficulty in decolorization degradation. In this paper, a novel composite nanomaterial catalyst of silver was prepared by using Angelica sinensis polysaccharide (ASP) as a reducing and stabilizing agent. And the optimum reaction conditions explored are VAgNO3 = 5 mL (300 mM) and vASP = 7% (w/v) for 6 h at 90 °C. In addition, the ASP-Ag nanocatalyst was characterized by several techniques. The results demonstrated that ASP-Ag nanoparticles were successfully synthesized. Degradation rate, which provides a numerical visualization of the percentage reduction in pollutant concentration. With the wrapping of ASP, the ultrasonic catalytic degradation rates of different organic dyes including rhodamine B (RB), methylene blue (MB), and methyl orange (MO) were from 88.2%, 88.7%, and 85.2% to 96.1%, 95.2% and 93.5% at room temperature, respectively. After the experiments, when cdyes = 10 mg/L, the highest degradation rate can be observed under cAPS-AgNPs = 10 mg/L with the most powerful cavitation frequency f = 59 kHz. The effect of ultrasonic frequency on the acoustic pressure distribution in the reactor was investigated by using COMSOL Multiphysis@ software to propose the mechanism of ultrasonic degradation and the mechanism was confirmed by OH· radical trapping experiments. It indicates that OH· produced by the ultrasonic cavitation effect plays a determinant role in the degradation. And then, the intermediate products of the dye degradation process were analyzed by gas chromatography and mass spectrometry (GC–MS), and the possible degradation processes of dyes were proposed. The resulting products of degradation are SO42−, NH4+, NO3−, N2, CO2 and H2O. Finally, the recycling degradation experiments showed that catalyst maintains a high degradation rate within reusing 5 cycles. Thus, this catalyst is highly efficient and recyclable.

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 μg/mL to 3200 μg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis. [ABSTRACT FROM AUTHOR]

Angelica sinensis polysaccharide (ASP) is a biomacromolecule that isolated from the roots of Angelica sinensis. This study aims to investigate its protective effect on kidney injury and its influence on BMP-7/ Smads/TGF-β1 signal pathway in irradiated rats. Total 60 Sprague Dawley (SD) rats were randomly divided into 5 groups: the normal (normal saline), model (normal saline), and low, medium, high dose of ASP groups (9.0, 18.0 and 36.0 mg/mL, 2.0 mL/kg·d, intragastric gavage once a day for 14 days). On the 15th day, all other groups received 60Co γ-ray irradiation with a total dose of 4.0 Gy except the normal group. The levels of NO synthase (NOS) and NO in serum, the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney of each group were detected with ELISA after 24 h of irradiation, and the protein expression levels of TGF-β1, phosphorylated (p-)Smad2, p-Smad2, p-Smad1, p-Smad5 and BMP7 in kidney were detected by western blotting. In the results, compared with the model group, NOS, NO and MDA contents were decreased in the middle and high dose groups while SOD contents were increased in low, middle and high dose groups. The levels of TGF-β, p-Smad2 and p-Smad3 were increased in low, middle and high dose groups while the levels of BMP7, p-Smad1 and p-Smad5 were decreased in middle and high dose groups. In conclusion, ASP can reduce the expression levels of TGF-β, p-Smad2 and p-Smad3 in kidney of rats induced by radiation, increase the expression levels of BMP7, p-Smad1 and p-Smad5, and resist the body injury caused by radiation by regulating BMP-7/Smads/TGF-β1 signal pathway. [ABSTRACT FROM AUTHOR]

The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus -induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae&#95;NK4A136 while reducing Erysipelatoclostridium . Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus -induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.

Objective To explore the antagonistic effect of Angelica sinensis polysaccharide (ASP) on brain aging induced by D-galactose (D-gal) in rats. Methods SD rats were randomly divided into control group, ASP group, aging model group, and ASP aging model group. Their spatial learning and memory abilities were detected by water maze test. The aging of brain tissue cells were detectded by aging-related β-galactosidase (SA-β-Gal) staining. The contents of SOD, MDA and GSH in hippocampal homogenate were measured by chromatography, and those of IL-1β and IL-6 in hippocampal homogenate were detected by ELISA. Southern blotting and TRAP-PCR were used to detect telomere length and telomerase activity in the hippocampal cells. Neural stem cells (NSCs) were isolated, cultured and identified from the brain tissue of SD fetal rats. The third-generation NSCs were divided into control group, ASP group, aging model group, and ASP aging model group. The content of MDA in the cells was determined by chromatography. The intracellular ROS level was determined by flow cytometry. qRT-PCR was used to detect the mRNA expression of p19, p21 and p53 of senescence related genes. Results Compared with the aging model group, the injection of ASP significantly improved the spatial learning and memory abilities of aging rats. The number of SA-β-Gal positive cells in the brain tissue was decreased (P < 0.05). The contents of SOD and GSH in the hippocampus were increased, but that of MDA was decreased (P < 0.05). The secretion levels of IL-1β and IL-6 were decreased (P < 0.05). The telomere length and telomerase activity were increased (P < 0.05). NSCs were successfully isolated and identified. Compared with the aging group, the MDA content and ROS level were significantly reduced in the ASP aging group (P < 0.05), and the mRNA levels of senescence-related genes p19, p21, and p53 were decreased (P < 0.05). Conclusion ASP may regulate cell telomere length and telomerase activity, down-regulate the expression of aging-related genes, reduce the expression of inflammatory factors, improve the cell's antioxidant capacity, and then antagonize the degeneration effect of D-gal on NSCs and hippocampal cells.

Rheumatoid arthritis (RA) is an autoimmune disease with a high incidence. Recent studies have demonstrated that diet can contribute to the development and progression of RA. Indeed, non-starch polysaccharides (NSPs) were known to be related to the improvement of RA. In this study, the collagen-induced rats were administrated with Angelica sinensis polysaccharide (ASP) at 200 mg/kg (L), 400 mg/kg (M), or 800 mg/kg (H). Results showed that ASP could reduce joint swelling and significantly inhibit anti-CII-antibodies and pro-inflammatory factors in RA, H group showed the best treatment among them. Further analysis using 16S rDNA sequencing suggested that ASP could shape the gut microbiota composition. Several key bacteria, including norank_f__norank_o__Clostridia_UCG-014 , Lactobacillus , norank_f__Oscillospiraceae, and norank_f__Desulfovibrionaceae , were found to be related to the development of RA. The colonic transcriptome showed that ASP could restore RA-induced intestinal dysfunction, such as tight junction disarrangement, by upregulating Cldn5. The balance between osteoblasts and osteoclasts might be modified by regulating the expression of Slit3 and Rgs18 to alleviate RA, which may be correlated with gut microbiota. Our results suggested that ASP improved RA by regulating gut microbiota and gene expression, revealing a positive relationship between dietary patterns and RA. [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]

Cationic PLGA nanoparticles-based delivery systems have been extensively employed as nanocarriers for drugs and antigens in recent years. Herein, we investigated the effects of polyethylenimine-coated PLGA nanoparticles containing Angelica sinensis polysaccharide (ASP) system (ASP-PLGA-PEI) on dendritic cells (DCs) activation and maturation, and further explored the changes of transcriptome and underlying mechanism of DCs activation based on RNA-seq. Our results demonstrated that ASP-PLGA-PEI obviously promoted the activation and maturation of DCs. Meanwhile, RNA-seq analysis results exhibited 2812 differentially expressed genes (DEGs) between ASP-PLGA-PEI and control group, and the DCs activation by ASP-PLGA-PEI stimulation mainly related to phagosome, antigen processing and presentation, proteasome, lysosome, protein processing in endoplasmic reticulum and other pathways by KEGG pathways analysis. Furthermore, ASP-PLGA-PEI nanoparticles increased the levels of pJAK2 protein, and the expression of co-stimulatory molecules and cytokines induced by ASP-PLGA-PEI nanoparticles were decreased with the presence of the inhibitor of JAK2/STAT3 signaling pathway. In addition, the nanoparticles were internalized by DCs mainly through the clathrin-mediated endocytosis and micropinocytosis. These results suggested that the DCs activation and maturation stimulated by ASP-PLGA-PEI were regulated via a complex interaction network, in which the JAK2/STAT3 signaling pathway played a crucial role. [ABSTRACT FROM AUTHOR]

Background: This study investigated the anti-aging effects of Angelica sinensis polysaccharide (ASP) on mouse hematopoietic stem cells (HSCs) and related mechanisms. Methods: Seventy-two C57BL/6J mice were randomly divided into the following three groups (n = 24 per group): control group; aging group, in which mice were irradiated with X-ray uniformly to establish the aging model of HSCs; and ASP group, in which mice were given 200 mg/kg ASP during irradiation. HSCs were collected by immunomagnetic beads, transmission electron microscopy was used to examine the morphological changes in HSCs, SA-β-Gal staining was used to detect the aging cells, immunofluorescence staining was used to detect the reactive oxygen species (ROS), and western blotting was used to evaluate the expression levels of sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1). Results: HSCs in the control group had an intact cytoplasmic structure and many mitochondria. In the aging group, HSCs had many vacuoles in the cytoplasm, and few and irregular mitochondria. In the ASP group, HSCs had a normal cytoplasmic structure and more mitochondria compared with the aging group. The aging group had a significantly higher positive rate of HSCs SA-β-Gal staining and ROS production than the control group (p < 0.05), but had lower expression of Sirt1 and FoxO1 (p < 0.05). These patho(physio)logical changes were ameliorated by ASP treatment (all p < 0.05). Conclusions: ASP inhibits irradiation-induced oxidative stress and aging of HSCs at least in part by regulating the Sirt1/FoxO1 pathway, thereby delaying aging of HSCs in mice. [ABSTRACT FROM AUTHOR]

Abstract Objective Chondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism. Method Human primary chondrocytes isolated from the articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3) II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localization, and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile, activation of the ERK 1/2 pathway was determined by western blot. The autophagy inhibitors, 3-methyladenine (3-MA), chloroquine (CQ), and a specific inhibitor of ERK1/2, SCH772984, were used to confirm the autophagic effect of ASP. Results The results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocyte proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of the ERK1/2 pathway. Conclusion ASP markedly rescued SNP-induced apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP as a potential therapeutic supplementation for OA treatment.

Angelica sinensis (AS) can improve the haematopoietic function, but the treatment mechanism is unknown. Transfusion dependency was estimated by Kaplan-Meier survival analyses and Cox proportional-hazard model in AS treated apalstic anemia (AA) patients. After that, the AA GEO database was analysed, the up differentially expressed genes (DEGs) of AA were combined with AS targets for the intersection of targets. After the AA mouse model was established, the effect of AS was confirmed by haematopoietic function tests. The same experiment plus mitochondrial apoptotic pathway tests in vivo were performed in Angelica sinensis polysaccharide (ASP)-treated mice, the key ingredient in AS. For in vitro experiment, bone marrow nucleated cells (BMNCs) were tested. Clinical data confirmed that the level of transfusion dependency and IL17A were lower in AS-users compared to non-AS users ( p < 0.001). The intersection of targets between AA and AS most concentrated on inflammation and apoptosis. Then, the same effect was found in AS treated AA mice model. In both in vivo and in vitro tests, ASP demonstrated the ability to mitigate P38/MAPK-induced Bax-associated mitochondrial apoptosis, while also reducing the levels of activated Th17 cells and alleviating abnormal cytokine levels. So, the protective effect of AS and ASP on hematopoietic function lies in their ability to prevent apoptosis.

Although iron oxide (Fe3O4) nanoparticles have broad application prospects as magnetic resonance imaging (MRI) contrast agent, their biocompatibility and biotoxicity still need to be improved. In this study, we prepared Fe3O4@Angelica sinensis polysaccharide nanoparticles (Fe3O4@ASP NPs) with a 9 nm Fe3O4 core and ASP as the coating material. The Fe3O4@ASP NPs are superparamagnetic, can be taken up by liver and spleen macrophages in the circulatory system in vivo, and are a good-biocompatibility and low-toxicity transverse relaxation time (T2) and T2-star (T2*) magnetic resonance imaging (MRI) contrast agent for the liver. The cytotoxicity assessment using HeLa cells and the pathological tests in mice validate that Fe3O4@ASP NPs have low toxicity and good biocompatibility in vivo, which can be attributed to the ASP as a natural polysaccharide with good biocompatibility and its function of protecting the liver. Fe3O4@ASP NPs are a potential new MRI contrast agent with high signal intensity in vivo. [ABSTRACT FROM AUTHOR]

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 μg/mL to 3200 μg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.

Angelica sinensis polysaccharide (ASP) is one of the main active components of Angelica sinensis (AS) that is widely used in traditional Chinese medicine. ASP is water-soluble polysaccharides, and it is mainly composed of glucose (Glc), galactose (Gal), arabinose (Ara), rhamnose (Rha), fucose (Fuc), xylose (Xyl) and galacturonic acid (GalUA). The extraction methods of ASP include hot water extraction and ultrasonic wave extraction, and different extraction methods can affect the yield of ASP. ASP has a variety of pharmacological activities, including hematopoietic activity, promoting immunity, antitumor, anti-inflammatory, antioxidant, anti-aging, anti-virus, liver protection, and so on. As a kind of natural polysaccharide, ASP has potential application as drug carriers. This review provides a comprehensive summary of the latest extraction and purification methods of ASP, the strategies used for monosaccharide compositional analysis plus polysaccharide structural characterization, pharmacological activities and drug carrier applications, and it can provide a basis for further study on ASP. [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]

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.

Purpose: To evaluate a Angelica sinensis polysaccharide aqueous extract as a preventive agent in experimentally induced urolithiasis using in- vitro and vivo models. Material and methods: Angelica sinensis polysaccharide was investigated in vitro to determine its antilithiatic effects on the formation and morphology of calcium oxalate (CaOx) crystals and was analyzed in vivo to determine its ability to prevent CaOx urolithiasis in rats subjected to ethylene glycol-induced urolithiasis. Potassium citrate administration was used in the positive control group. The urolithiasis-related biochemical parameters were evaluated in the rats urine, serum and kidney homogenates. Kidney sections were subjected to histopathological and immunohistochemical analyses, and urolithiasis-related phospho-c-Jun NH2-terminal protein kinase and kidney injury molecule-1proteins were evaluated by Western blot analyses. Results: Angelica sinensis polysaccharide exhibited concentration-dependent inhibition of CaOx crystal formation. The in vitro assay revealed significant inhibition of crystal formation (6.99 ± 1.07) in the group treated with 4.0 mg/mL Angelica sinensis polysaccharide extract compared with the control group (58.38 ± 5.63; p .05). The rats administered the extract of Angelica sinensis polysaccharide showed significantly decreased pathological change and CaOx deposition (p

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

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]

Nonalcoholic fatty liver disease (NAFLD) is one of the prevalent and typical chronic liver diseases. In this study, we extracted a novel Angelica sinensis polysaccharide (ASP) with low molecular weight (MW) of 3.2 kDa through optimized "one‐step" purification process. The major monosaccharide components of ASP were mannose, rhamnose, glucuronic acid, galactose, arabinose, and xylose with weight ratio of 0.23:0.17:14.41:0.39:1.68:0.87, respectively. Herein, "small" ASP could serve as an effective therapeutic option for NAFLD both in free fatty acid‐induced L02 models and in high‐fat diet‐induced mice models. Results revealed that low MW ASP dose‐dependently decreased TG, TC in vitro and TG, TC, ALT, HDL‐C, and LDL‐C in vivo. Oil Red O‐positive area and Nile red fluorescence intensity decreased in ASP treatment groups both in vitro and in vivo which suggested ASP could reduce lipid accumulation and fatty regeneration. Hematoxylin–eosin staining results shown a decrease in hepatocytes ballooning indicating that ASP could ameliorate liver lipid degeneration. Briefly, a novel polysaccharide with low MW was successfully obtained which can prospectively act as NAFLD therapy. [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]

Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of lung fibroblasts and extracellular matrix deposition. Angelica sinensis polysaccharide (ASP), the major bioactive component that can extracted from roots of angelica, plays functional roles in immunomodulation, anti-tumor activity, and hematopoiesis. Emerging evidence has suggested that long noncoding RNAs (lncRNAs) play important roles in pathophysiological processes in various diseases. However, the roles of lncRNAs and ASP in IPF remain poorly understood. In the present study, we investigated the effects of ASP in IPF, as well as their functional interactions with lncRNA DANCR (differentiation antagonizing non-protein coding RNA). IPF models were established by treating Sprague-Dawley rats with BLM and treating alveolar type ? epithelial (RLE-6TN) cells with TGF-ß1. Our results showed that ASP treatment suppressed pulmonary fibrosis in rats and fibrogenesis in RLE-6TN cells. The lncRNA DANCR is downregulated after ASP treatment in both rat lung tissues and RLE-6TN cells, and DANCR overexpression dramatically reversed the suppressive effects of ASP in IPF. Mechanistically, DANCR directly binds with AUF1 (AU-binding factor 1), thereby upregulating FOXO3 mRNA and protein levels. Moreover, overexpression of AUF1 or FOXO3 reversed the functional effects induced by ASP treatment. In conclusion, our findings showed that DANCR mediates ASP-induced suppression of IPF via upregulation of FOXO3 protein levels in an AUF1-dependent manner. Therefore, DANCR could serve as a promising therapeutic target in IPF treatment with ASP. [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]

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]

Graphical abstract Abstract Nanoparticles (NPs)-based vaccine delivery systems are widely used for their ability to control the release of antigens and promote immune responses against cancer or infectious diseases. In this study, the immunopotentiator Angelica sinensis polysaccharide (ASP) and model protein antigen ovalbumin (OVA) were encapsulated into Poly(lactic-co-glycolic acid) (PLGA) to formulate the novel NPs-based vaccine delivery system (ASP-PLGA/OVA). These formulations were subcutaneously administered to mice, then the magnitude and kinetics of antibody and cellular immune responses were assessed. The ASP-PLGA/OVA NPs were pherical in shape with smooth surfaces, approximately 225.2 nm in average size, negatively charged (around −11.27 mV), and the encapsulation efficiency of OVA at around 66.28%, respectively. Furthermore, ASP-PLGA/OVA NPs could keep stable at 4 °C over 30 days and provide a sustained and controlled release of OVA from the NPs. The results demonstrated that mice immunized with ASP-PLGA/OVA NPs could significantly enhance lymphocyte proliferation and improve the ratio of CD4+ to CD8+ T cells, thereby ASP-PLGA/OVA NPs could induce a strong cellular immune response. Moreover, the ASP-PLGA/OVA NPs could induce vigorous and long-term IgG immune responses with a mixed Th1 and Th2 responses and up-regulate the levels of Th-associated cytokines. These results suggested that ASP-PLGA/OVA NPs, which stimulated strong and continuous antibody responses and induced cellular immune responses, could potentially serve as an efficient and safe vaccine delivery and adjuvant system against infections and diseases. [ABSTRACT FROM AUTHOR]

Combination of chemotherapy and immunotherapy has been a promising strategy in cancer treatment. Polysaccharides from Angelica sinensis (AP), a well-known Chinese herbal medicine, have been proved to have good immunomodulatory activity. In the present study, an enzyme-sensitive tumor-targeting nano drug delivery system (AP-PP-DOX (doxorubicin), PP stood for peptide) was constructed. In this system, Angelica polysaccharides act as not only carriers to targeted delivery of drugs to tumor tissue but also effectors to improve tumor microenvironment and enhance immune function, resulting in synergistic antitumor effect with chemotherapy drugs. The structure of this conjugate was confirmed by FI-IR and 1H-NMR. The particle size and zeta potential of the nanoparticles were 129.00 ± 3.32 nm and −28.45 ± 0.22 mV, respectively. Doxorubicin (DOX) and AP could be quickly released from the AP-PP-DOX under the presence of matrix metalloproteinase 2 (MMP2). The released DOX showed good antitumor efficacy in vitro. The treatment of released AP moiety increased the expression of IL-2, while that of IL-10 was decreased, showing potential in restoring Th1/Th2 immune balance in tumor microenvironment. In a word, this drug delivery system, with specific tissue targeting and tumor microenvironment improvement, will open a new avenue for combination treatment of cancer.

Purpose: To evaluate a Angelica sinensis polysaccharide aqueous extract as a preventive agent in experimentally induced urolithiasis using in- vitro and vivo models. Material and methods: Angelica sinensis polysaccharide was investigated in vitro to determine its antilithiatic effects on the formation and morphology of calcium oxalate (CaOx) crystals and was analyzed in vivo to determine its ability to prevent CaOx urolithiasis in rats subjected to ethylene glycol-induced urolithiasis. Potassium citrate administration was used in the positive control group. The urolithiasis-related biochemical parameters were evaluated in the rats urine, serum and kidney homogenates. Kidney sections were subjected to histopathological and immunohistochemical analyses, and urolithiasis-related phospho-c-Jun NH2-terminal protein kinase and kidney injury molecule-1proteins were evaluated by Western blot analyses. Results: Angelica sinensis polysaccharide exhibited concentration-dependent inhibition of CaOx crystal formation. The in vitro assay revealed significant inhibition of crystal formation (6.99 ± 1.07) in the group treated with 4.0 mg/mL Angelica sinensis polysaccharide extract compared with the control group (58.38 ± 5.63; p < .05). In vivo, after treatment with ethylene glycol for 28 days, urinary oxidative stress, oxalate, creatinine, urea and urolithiasis-related protein were significantly increased (p < .05), except for serum oxidative stress (p > .05). The rats administered the extract of Angelica sinensis polysaccharide showed significantly decreased pathological change and CaOx deposition (p < .05) compared with the urolithiatic rats. Significantly reduced levels of urinary oxidative stress, oxalate, creatinine, urea and urolithiasis-related protein were observed in the Angelica sinensis polysaccharide treatment groups (p < .05) compared with the nephrolithic rats. Conclusion: The results presented here suggest that Angelica sinensis polysaccharide has the potential to inhibit CaOx crystallization in vitro and may present anti-urolithiatic effects in vivo. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the oxidative stress in human osteoarthritis (OA) chondrocytes and the antioxidant effect of angelica sinensis polysaccharide (ASP) on it. Human OA chondrocytes and human normal chondrocytes induced by hydrogen peroxide (H 2 O 2 ) alone or treated with ASP were cultured, then they were measured with cell viability, levels of reactive oxygen species (ROS), nitric oxide (NO) and malondialdehyde (MDA) production, activities of inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD) and catalase (CAT), expression of related genes, such as collagen type II (Col2a1), Aggrecan, iNOS, SOD, CAT and peroxisome proliferator-activated receptor gamma (PPARγ). We found that the production of ROS, NO, and MDA and the activity of iNOS, SOD and CAT were significantly increased in OA chondrocytes compared with human normal chondrocytes. When treated with H 2 O 2 , human chondrocytes exhibited acute oxidative stress injure, which was similar to OA chondrocytes. Pretreatment with ASP before H 2 O 2 alleviated oxidative stress and protected human chondrocytes. The activity of PPARγ was decreased in OA chondrocytes and increased when treated with ASP. In conclusion, oxidative stress is an important pathogenesis of OA, and ASP inhibits H 2 O 2 -mediated injury in human chondrocytes. Our data also suggest that PPARγ participates in oxidation and anti-oxidation of OA. [ABSTRACT FROM AUTHOR]

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload. [ABSTRACT FROM AUTHOR]

Abstract: Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH‐SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA‐H19), microRNA (miR)‐675, and CD44 were assessed. Then, effects of miR‐675 overexpression on AP‐treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR‐675 was finally explored. Cell viability was reduced by 200–500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA‐H19 and miR‐675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH‐SY5Y cells through downregulating miR‐675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR‐675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR‐675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH‐SY5Y cells through miR‐675‐mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR‐675. [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]

Angelica sinensis polysaccharide (ASP) was prepared by hot water extraction. Then, high-performance liquid chromatography and ion chromatography analyses were conducted, and the results indicated that ASP is a heteropolysaccharide, has a molecular mass of 82,000 Da and consists of arabinose, galactose and glucose (molar ratio of 6:1:1). The effects of ASP on the nonspecific immunity of white shrimps ( Litopenaeus vannamei ) were investigated by feeding them with ASP-containing diets (0.5, 1 and 1.5 g/kg) during a 12-week breeding experiment. Oral ASP administration significantly improved the survival rate, phenoloxidase activity, superoxide dismutase activity, glutathione peroxidase level, disease resistance against V. alginolyticus, total haemocyte count and number of hyaline cells, semigranular cells and granular cells ( p  < .05). ASP exhibits immunostimulatory effects on Pacific white shrimps ( L. vannamei ) and may thus be used as a diet supplement for them. [ABSTRACT FROM AUTHOR]

Scaffolds made from single hydroxyapatite (HAp) possess neither biological properties of bone nor functions of promoting vascularization and inhibiting immune rejection. To overcome these drawbacks of HAp,Angelica sinensispolysaccharide (ASP)/HAp composite scaffolds were prepared and its application possibility in bone tissue engineering was studied. The scaffolds were examined by mechanical test, releasing test, degradation test, and histological evaluation. The results showed that the scaffolds had good degradation and ASP releasing. The histological examination indicated that ASP/HAp material could effectively promote vascularization, hematopoiesis, and osteogenesis in mice. In conclusion, the composite material could be used for bone tissue engineering with good prospect. [ABSTRACT FROM PUBLISHER]

In this study, angelica sinensis polysaccharide (ASP) was encapsulated into the Poly (lactic-co-glycolicacid) (PLGA) to constitute the ASP-PLGA. The aim of the study is to obtain optimal encapsulation efficiency of ASP-PLGA by optimizing the preparation conditions and investigate the immunological enhancement activity of ASP-PLGA. To obtain the optimal processing parameters, the parameters, such as the ratio of organic phase (o) to internal water phase (w 1 ), the ratio of external water phase (w 2 ) to organic phase (o) and the concentration of Pluronic F68 (F68) (w/v) were examined through response surface methodology (RSM). The optimum preparation conditions of ASP-PLGA for maximizing encapsulation efficiency (EE) was as follows:ratio of organic phase (o) to internal water phase (w 1 ) at 10:1, ratio of external water phase (w 2 ) to organic phase (o) at 11:1, the concentration of F68 at 0.8% and the experimental EE 67.89 ± 0.48% was achieved. In addition, the results showed that ASP-PLGA could significantly promote the lymphocytes proliferation and increase the ratio of CD4 + to CD8 + T cells compared with ASP and blank PLGA. This study provided strong evidence that the immunological enhancement of ASP was significantly improved through establishing a drug delivery system with PLGA. [ABSTRACT FROM AUTHOR]