Effects Of Angelica Sinensis Polysaccharide Research Articles

Angelica sinensis Polysaccharide Suppresses Pyroptosis in Myocardial Ischemia/Reperfusion Injury via the FN1/NF-κB/NLRP3 Pathway

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.

Protective effect of Angelica sinensis polysaccharide on pregnant rats suffering from iron deficiency anemia via regulation of the hepcidin-FPN1 axis

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.

Angelica sinensis polysaccharide ameliorates myocardial ischemia-reperfusion injury in rats by inhibiting TLR4/NF-κB

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 hypoxia-reoxygenation (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.

Polysaccharide from Angelica sinensis with medicinal and edible purposes ameliorated NAFLD by the bile acids mediated activation of FXR

Liver and gut communicates with each other through metabolites and the gut-liver axis plays a crucial role in lipid metabolism. Enterohepatic bile acid circulation is an important constitution of gut-liver axis. Farnesoid X receptor (FXR)，a bile acid mediated nuclear receptor, is promising therapeutic targets for the non-alcoholic fatty liver disease (NAFLD). More and more studies have confirmed the effects of Angelica sinensis polysaccharide (ASP) on liver protection and lipid regulation. However, little attention has been paid to the role of ASP on the gut-liver axis, which is crucial to clarify how ASP play a role in liver protection after oral administration. In vivo and in vitro models of NAFLD were established to examine the effect of ASP on hepatic fat accumulation. Our results showed that ASP could alleviate liver fat accumulation. However, the expression of FXR was not changed when ASP directly acting on hepatocytes, while ASP could change the expression of FXR in liver and intestine of mice after oral administration. In addition, our results showed that ASP could promote the excretion of bile acids, thereby increasing cholesterol metabolism. Our research provided a new concept for the mechanism of ASP regulating liver lipid metabolism and exerting liver protection.

Angelica Sinensis Polysaccharide Suppresses the Aging of Hematopoietic Stem Cells Through Sirt1/FoxO1 Signaling.

This study investigated the anti-aging effects of Angelica sinensis polysaccharide (ASP) on mouse hematopoietic stem cells (HSCs) and related mechanisms. 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). 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). 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.

Angelica Sinensis Polysaccharide Mediates Sirtl to Inhibit P53/P21 Pathway and Delay Hematopoietic Stem Cell Aging

To study the effect of Angelica sinensis polysaccharide (ASP) on the expression of Sirt1/p53/p21 in radiation-induced aging hematopoietic stem cells (HSCs) of mice, and to explore the possible mechanism of ASP regulating the aging of HSCs. Methods: C57BL/6J mice were randomly divided into control group, model group and ASP group. The model group was irradiated with X-ray 3.0Gy/8F to establish the aging model of HSCs in mice. ASP group was given ASP intragastric administration during irradiation; The control group and the model group were given equal volume of normal saline. HSCs were sorted by immunomagnetic beads, and cell cycle was detected by flow cytometry The aging cells were observed by α-galactosidase staining. The directional differentiation ability of HSCs was observed by mixed colony culture (CFU-Mix). The expression of Sirtl, p53 and p21 protein was detected by Western blot. Results: Compared with the control group. X-ray can significantly increase the proportion of HSCs Gi cells, the rate of SA-α-Gal positive cells and the expression of p53 and p21 protein in aging group (P&lt;0.05).The expression of Sirtl and mixed colony forming ability were decreased (P&lt;0.05). Compared with the model group, ASP inhibited the increase of aging HSCs Gicell ratio, SA-fJ-Gal positive cell rate and p53 and p21 protein expression (P&lt;0.05). At the same time, Sirtl expression and mixed colony forming ability were increased (P&lt;0.05). conclusion: ASP may inhibit p53/p21 pathway and delay the aging of mouse HSCs by regulating Sirtl.

Angelica sinensis Polysaccharide Alleviates Myocardial Fibrosis and Oxidative Stress in the Heart of Hypertensive Rats

This research is aimed at studying the effect of Angelica sinensis polysaccharide (ASP) extracted from the Lixinshui prescription on cardiac disease induced by hypertension in rats. Rat models of cardiovascular disease were established, and the associated factors were measured. The data showed that ASP treatment increased the ejection fraction and short axis shortening rate, while decreasing the LV end-diastolic diameter, LV end-systolic diameter, LV end-diastolic volume, and LV end-systolic volume in HHD rats. ASP downregulated the expression level of TGF-β1, alpha-smooth muscle actin (α-SMA), collagen I, fibronectin, vimentin, Bax, cleaved caspase-9, and cleaved caspase-3 and upregulated the expression level of Bcl-2 in LV of HHD rats. Meanwhile, ASP increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the level of malondialdehyde (MDA), tissue endogenous hydrogen peroxide (H2O2), and reactive oxygen species (ROS). Our findings indicated that ASP could prevent hypertensive heart disease by inhibiting myocardial fibrosis, suppressing the myocardial apoptosis, and alleviating oxidative stress.

Regulatory Effect of Angelica sinensis Polysaccharide on Bcl-2/Bax/Caspase-3 Signal Pathway in Spleen of Rats with Radiation Injury

To investigate the protective effect of Angelica sinensis polysaccharide (ASP) on spleen injury and its influence of Bcl-2/Bax/Caspase-3 signal pathway in radiation rats, 60 Sprague Dawley (SD) rats were divided into 5 groups randomly: the normal group, the model group, low-, middle- and high- dose of ASP groups. On the 15th day after the appropriate medication, all the rats except the normal group received the 60Co γ-ray irradiation once with a total dose of 4.0Gy. The levels of NF-kBp65 and IKKa in serum, the contents of MDA, GSH and SOD in spleen of each group were detected with ELISA after 24 h of irradiation, and the protein expression levels of Bcl-2, Bax, Caspase-3, HSPBP1 and TIMM8B in spleen of each group were detected by western blotting. The results showed that compared with the model group, NF-kBp65, IKKa and MDA contents were decreased while GSH and SOD contents were increased in the middle and high dose groups. The level of Bcl-2 and TIMM8B were increased while Bax, caspase-3 and HSPBP1 were decreased in all groups. In conclusion, Angelica sinensis polysaccharide can reduce the expression levels of Bax and caspase-3, while increase the level of Bcl-2 in spleen of rats induced by radiation and antagonize the body injury caused by radiation by regulating Bcl 2/Bax/Caspase 3 signaling pathway.

Effect of Angelica sinensis polysaccharide on the osteogenic differentiation of bone marrow mesenchymal stem cells of rats with high glucose levels

This study aims to evaluate the effect of Angelica sinensis polysaccharide (ASP) on the osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) of rats with high glucose levels. Rat BMSCs were isolated and identified by osteogenic and adipogenic differentiation. Then, the BMSCs were divided into three groups as follows: normal control group (5.5 mmol·L⁻¹ glucose), high glucose group (25.5 mmol·L⁻¹ glucose), and ASP+high glucose group (25.5 mmol·L⁻¹ glucose +40 mg·L⁻¹ ASP). The proliferation activities of the BMSCs were detected by CCK8. Alizarin red staining, and alkaline phosphatase activity were used in the examination of osteogenic activity. Quantitative real time-polymerase chain reaction was used to detect the expression levels of the osteogenic genes (Runx2, Osx, OCN, Col-Ⅰ) and the key factors of Wnt/β-catenin signal pathway (CyclinD1, β-catenin). In vivo, a type 2 diabetes rat model was established. The rats were divided into three groups, namely, the normal control group (normal rats), diabetes group (diabetic rats), diabetes+ASP group (diabetic rats, ASP feeding). Then, the tibia bone defect was established. The repair of bone defects in each group was observed through histological examination. The proliferation of BMSCs was higher in the high glucose group and ASP+high glucose group than in the normal control group (P<0.05). No significant difference was observed between the high glucose group and ASP+high glucose group (P>0.05). The number of calcium nodules of BMSCs; alkaline phosphatase activity; and the mRNA expression of Runx2, OCN, Osx, Col-Ⅰ, CyclinD1, β-catenin in the high glucose group were lower than those in the normal control and ASP+high glucose groups (P<0.05). No significant difference was observed between the normal control and ASP+high glucose groups (P>0.05). The bone mass was significantly lower in the bone defect of the diabetes group than in the bone defect of the normal control or diabetes+ASP group (P<0.05). No statistical difference was found between the normal control and diabetes+ASP groups (P>0.05). ASP can promote the osteogenic differentiation of rat BMSCs under high glucose culture and induce bone regeneration in rats with type 2 diabetes. These features may be related to the activation of the Wnt/β-catenin signaling pathway.

Oral administration of Angelica sinensis polysaccharide protects against pancreatic islets failure in type 2 diabetic mice: Pancreatic β-cell apoptosis inhibition

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.

Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction.

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent–target–disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo. In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion: In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP’s effects could be mediated via the activation of AMPK-PGC1α pathway.

Correction of Anemia in Chronic Kidney Disease With Angelica sinensis Polysaccharide via Restoring EPO Production and Improving Iron Availability.

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

Oxidative stress in osteoarthritis and antioxidant effect of polysaccharide from angelica sinensis

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 (H2O2) 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 H2O2, human chondrocytes exhibited acute oxidative stress injure, which was similar to OA chondrocytes. Pretreatment with ASP before H2O2 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 H2O2-mediated injury in human chondrocytes. Our data also suggest that PPARγ participates in oxidation and anti-oxidation of OA.

Angelica sinensis polysaccharide protects against acetaminophen-induced acute liver injury and cell death by suppressing oxidative stress and hepatic apoptosis in vivo and in vitro

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.

The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice

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 Polysaccharides Ameliorate Stress-Induced Premature Senescence of Hematopoietic Cell via Protecting Bone Marrow Stromal Cells from Oxidative Injuries Caused by 5-Fluorouracil.

Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells. Tumor-suppressive doses of 5-FU inhibited the growth of HS-5 in a dose-dependent and time-dependent manner. 5-FU induced HS-5 apoptosis and also accumulated cellular hallmarks of senescence including cell cycle arrest and typical senescence-associated β-galactosidase positive staining. The intracellular reactive oxygen species (ROS) was increased in 5-FU treated HS-5 cells and coinstantaneous with attenuated antioxidant capacity marked by superoxide dismutase and glutathione peroxidase. Oxidative stress initiated DNA damage indicated by increased γH2AX and 8-OHdG. Oxidative damage of HS-5 cells resulted in declined hematopoietic stimulating factors including stem cell factor (SCF), stromal cell-derived factor (SDF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), however, elevated inflammatory chemokines such as RANTES. In addition, gap junction channel protein expression and mediated intercellular communications were attenuated after 5-FU treatment. Significantly, co-culture on 5-FU treated HS-5 feeder layer resulted in less quantity of human umbilical cord blood-derived hematopoietic cells and CD34+ hematopoietic stem/progenitor cells (HSPCs), and SIPS of hematopoietic cells. However, it is noteworthy that ASP ameliorated SIPS of hematopoietic cells by the mechanism of protecting bone marrow stromal cells from chemotherapeutic injury via mitigating oxidative damage of stromal cells and improving their hematopoietic function. This study provides a new strategy to alleviate the complication of conventional cancer therapy using chemotherapeutic agents.

RETRACTED: Polysaccharide from Angelica sinensis ameliorates high-fat diet and STZ-induced hepatic oxidative stress and inflammation in diabetic mice by activating the Sirt1–AMPK pathway

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief because of duplication of data already published in the following paper in Food & Function: “Protective effects of Angelica sinensis polysaccharide against hyperglycemia and liver injury in multiple low-dose streptozotocin-induced type 2 diabetic BALB/c mice” by Wang K et al. in Food Funct 2016; 7; 4889-4897. The following data are the same in both papers: 1 The results of liver slices of oil red O staining in JNB Figure 1 are the same as Figure 6 in Food & Function. 2 JNB Figures 1 A and B are the same as Figure 7 B in the paper in Food & Function. 3 JNB Table 1 is the same as data presented in Figures 6 A-D and parts of Figure 3 A in the paper in Food & Function.

Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model.

Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1) ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS), 8-OHdG, and 4-HNE were declined, (2) ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs) marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3) ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice.

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

Protective effect of Angelica sinensis polysaccharide against liver injury induced by D-galactose in aging mice and its mechanisms

To investigate the protective effect of Angelica sinensis polysaccharide (ASP) against liver injury induced by D-galactose in aging mice and its mechanisms. Male C57BL/6J were randomly divided into three groups with 10 mice in each group. In the D-galactose model group, the mice were subcutaneously injected with D-galactose (120 mg/kg) qd×42; in the ASP+D-galactose group, from the 8th day of the establishment of D-galactose model, the mice were subcutaneously injected with ASP (120 mg/kg) qd×35. In the normal control group, the mice were subcutaneously injected with isotonic saline of the same volume at the same time point. On the 2nd day after the injection was finished, the ocular blood was collected to prepare serum and measure the content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil). The liver tissue homogenate was prepared to measure the content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and advanced glycation end products (AGEs). A paraffin section of liver tissue was prepared; HE staining was performed to observe the pathomorphological changes of the liver, periodic acid-Schiff staining (PAS) was used to observe the changes in glycogen in the liver, and a transmission electron microscope was used to observe the hepatocyte ultrastructure. The D-galactose model group had increased content of ALT, AST, and TBil, reduced activities of SOD and GSH-Px, an increased content of MDA, and severe liver injuries; the hepatocytes showed degenerative changes, the amount of glycogen in the liver decreased, and the accumulation of AGEs increased. The ASP+D-galactose group had reduced content of ALT, AST, and TBil, increased activities of SOD and GSH-Px, and reduced content of MDA and AGEs; the amount of glycogen in the liver increased, and liver injury and hepatocyte injury were alleviated. ASP can antagonize the liver injury induced by D-galactose in aging mice, and its mechanism may be related to the inhibition of oxidative stress.