Screening of polysaccharides from the differently processed products of Angelica sinensis with the best liver protection effect on chicken and the intervention mechanism study based on tandem mass tag proteomics and multiple reaction monitoring approach.

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.

Angelica Sinensis Polysaccharide-Based Nanoparticles for Liver-Targeted Delivery of Oridonin.

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.

Angelica sinensis polysaccharides prevents hematopoietic regression in D-Galactose-Induced aging model via attenuation of oxidative stress in hematopoietic microenvironment.

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-ß-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.

Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through PPARγ/SOD2/ROS pathways.

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.

Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen-related receptor α expression in liver.

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.

Angelica sinensis Polysaccharide and Astragalus membranaceus Polysaccharide Accelerate Liver Regeneration by Enhanced Glycolysis via Activation of JAK2/STAT3/HK2 Pathway.

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.

A Nano Drug Delivery System Based on Angelica sinensis Polysaccharide for Combination of Chemotherapy and Immunotherapy.

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.

Rational Design of PLGA Nanoparticle Vaccine Delivery Systems To Improve Immune Responses.

Nanoparticle-based vaccine delivery systems have been extensively used to promote and induce immune responses to protein antigens. The properties of the nanoparticles, such as size, surface charge, and antigen loading mode, have been proved to significantly influence the adjuvant effect and immunoreactivity of nanoparticle-based vaccine delivery systems. The purpose of the study was to investigate how the surface charge and antigen loading mode of nanoparticles impact the immune responses. In this study, three ovalbumin (OVA)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles with different surface charges and antigen loading modes were developed. The three nanoparticles were designed as antigen encapsulated with negatively charged (Angelica sinensis polysaccharide (ASP)-PLGA/OVA), antigen encapsulated with polyethylenimine (PEI)-coated (ASP-PLGA/OVA-PEI), and antigen adsorbed on PEI-coated (ASP-PLGA-PEI-OVA) nanoparticles. The Angelica sinensis polysaccharide (ASP) was used as the immunopotentiator and encapsulated into three nanoparticles. The results demonstrated that both PEI-coated (positively charged) nanoparticles promoted the antigen escape from the endosome, which led to the cytoplasmic antigen delivery to generate cross presentation, compared to negatively charged nanoparticles. In addition, PEI-coated nanoparticles activated the DCs in lymph nodes 5 days after the primary vaccination. In vivo experiments demonstrated that both antigen-encapsulated nanoparticles induced more potent and long-term antigen-specific antibody responses, compared to that of antigen-adsorbed nanoparticles. Thus, the PEI-coated and antigen-encapsulated nanoparticles (ASP-PLGA/OVA-PEI) as a vaccine adjuvant delivery system have the potential to induce strong and long-term humoral and cellular immune responses.

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 polysaccharide inhibits proliferation, migration, and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y.

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 ß (KIF1Bß) 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, KIF1Bß might be a target of miR-675.

Stimulating effects of polysaccharide from Angelica sinensis on the nonspecific immunity of white shrimps (Litopenaeus vannamei).

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.

Protective potential of Angelica sinensis polysaccharide extract against ethylene glycol-induced calcium oxalate urolithiasis.

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.

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 ß-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.

Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation.

Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP response element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer.

Polysaccharides from Angelica and Astragalus exert hepatoprotective effects against carbon-tetrachloride-induced intoxication in mice.

This study aimed to investigate the effects of polysaccharide from Angelica and Astragalus (AAP) on carbon tetrachloride (CCl4) induced liver damage in mice. A total of 120 Kunming mice were randomly distributed among 6 groups comprising (i) the normal control mice, (ii) the CCl4 treatment group, (iii) the bifendate treatment group, (iv) the AAP treatment group, (v) the Angelica sinensis polysaccharide (ASP) treatment group, and (vi) the Astragalus membranaceus polysaccharide (AMP) treatment group. AAP, ASP and AMP were administered to mice treated with CCl4. The activities of alanine transaminase (ALT) and aspartate transaminase (AST) in the serum, and superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver tissues were quantified, as well as the liver index. Hepatic histological changes were observed by staining liver sections with hematoxylin and eosin. Our results show that bifendate, AAP, ASP, and AMP significantly decreased the activities of MDA, AST, and ALT, and enhanced the activity of SOD in CCl4-treated mice. Bifendate, AAP, ASP, and AMP consistently ameliorated the liver injuries induced with CCl4. Notably, the hepatoprotective effect of AAP was stronger than that of bifendate, ASP, or AMP. In addition, AAP alleviated liver inflammation and decreased the liver indexes of mice induced with CCl4. These effects were at least partly due to the antioxidant properties of AAP in scavenging free radicals to ameliorate oxidative stress and to inhibit lipid peroxidation.

Angelica sinensis polysaccharide combined with cisplatin reverses cisplatin resistance of ovarian cancer by inducing ferroptosis via regulating GPX4.

Cisplatin (DDP) resistance poses a significant challenge in the treatment of ovarian cancer. Studies have shown that the combination of certain polysaccharides derived from plants with DDP is an effective approach to overcoming drug resistance in some cancers. Angelica sinensis (Oliv.) Diels has been used for centuries in China to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis, can inhibit various forms of cancer. However, the impact of ASP on ovarian cancer remains unexplored. Through both in vitro and in vivo experiments, our study revealed the capability of ASP to effectively reversing DDP resistance in cisplatin-resistant ovarian cancer cells, while exhibiting acceptable safety profiles in vivo. To elucidate the mechanism underlying drug resistance reversal, we employed RNA-seq analysis and identified GPX4 as a key gene. Considering the role of GPX4 in ferroptosis, we conducted additional research to explore the effects of combining ASP with DDP on SKOV3/DDP cells. In summary, our findings demonstrate that the combination of ASP and DDP effectively suppresses GPX4 expression in SKOV3/DDP cells, thereby reversing their resistance to DDP.

Degradation of Angelica sinensis polysaccharide: Structures and protective activities against ethanol-induced acute liver injury.

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.

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.

Exploring the mechanism by which Angelica sinensis improves haematopoietic function in aplastic anaemia.

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.

Preparation and evaluation of Angelica sinensis polysaccharide-modified chitosan sponge for acute liver injury protection.

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 CCl4-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.