Recent efficacy and long-term survival of Astragalus polysaccharide combined with gemcitabine and S-1 in pancreatic cancer

BACKGROUND Pancreatic cancer is a highly malignant tumor with a rapid progression rate and a high susceptibility to infiltration and metastasis.Astragalus polysaccharide(APS),a pure Chinese medicine preparation primarily made from the traditional Chinese herb Astragalus,plays a positive role in the treatment of many malignant tumors.AIM To explore the recent efficacy of APS combined with gemcitabine plus tegafur gimeracil oteracil potassium capsule(S-1)(GS)regimen in the treatment of pancreatic cancer and assess its effect on the immune function and long-term survival of patients.METHODS A total of 97 patients who were diagnosed with pancreatic cancer and received GS chemotherapy at The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)from March 2021 to December 2021 were included in the retrospective analysis.Among them,41 patients received APS combined with GS chemotherapy,and 56 patients received GS chemotherapy only.The recent efficacy,immune function,adverse reactions,and long-term survival were compared among these patients.RESULTS After 4 cycles of treatment,the objective response rate of patients receiving the combined therapy of APS and GS was 51.22%,and the disease control rate(DCR)was 56.10%,higher than those of patients receiving the monotherapy with GS alone(30.36%and 35.71%,respectively).Besides,the percentages of CD3+T cells(50.18%±9.57%)and CD4+T cells(31.52%±5.33%)in the peripheral blood of patients receiving the combined therapy of APS and GS were higher compared with those treated with GS regimen alone[(44.06%±8.55%)and(26.01%±7.83%),respectively].Additionally,the incidences of leukopenia,thrombocytopenia,and fatigue in patients receiving the combined therapy of APS and GS were significantly lower than those in patients receiving the monotherapy of GS alone(17.07%,9.76%,31.71%vs 37.50%,28.57%,60.71%).Moreover,the median survival time of patients receiving the combined therapy of APS and GS was 394 days,significantly longer than that of patients receiving the mono-therapy of GS alone(339 days)(hazard ratio:0.66;95%CI:0.45-0.99;P=0.036).All these differences were statistically si-gnificant(P<0.05).CONCLUSION The combined therapy of APS and GS improved the recent efficacy and long-term survival of patients with pancreatic cancer and alleviated chemotherapy-induced immune suppression and adverse reactions.

Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice

AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.

Effect of Astragalus polysaccharides on Erythrocyte Immune Adherence of Chickens Inoculated with Infectious Bursal Disease Virus

Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.

Synergistic protection of astragalus polysaccharides and matrine against ulcerative colitis and associated lung injury in rats

BACKGROUND Ulcerative colitis(UC)is a main form of inflammatory bowel disease.Due to complicated etiology and a high rate of recurrence,it is quite essential to elucidate the underlying mechanism of and search for effective therapeutic methods for UC.AIM To investigate the effects of astragalus polysaccharides(APS)combined with matrine on UC and associated lung injury.METHODS UC was induced in rats by colon mucosal tissue sensitization combined with trinitro-benzene-sulfonic acid-ethanol.Then,the effects of the treatments of salazopyrine,APS,matrine,and APS combined with matrine on histopathological changes of lung and colon tissues,disease activity index(DAI),colon mucosal damage index(CMDI),serum endotoxin(ET)level,serum diamine oxidase(DAO)activity,the contents of tumor necrosis factor-αand interleukin-1β,and the activities of myeloperoxidase,superoxide dismutase,and malondialdehyde in lung tissues,as well as the protein expression of zonula occludens(ZO)-1,Occludin,and trefoil factor 3(TFF3)were detected in UC rats.RESULTS The treatments of salazopyrine,APS,matrine,and APS combined with matrine reduced DAI scores and improved histopathological changes of colon and lung tissues,as well as decreased CMDI scores,ET levels,and DAO activities in UC rats.Moreover,in lung tissues,inflammatory response and oxidative stress injury were relieved after the treatments of salazopyrine,APS,matrine,and APS combined with matrine in UC rats.Furthermore,the expression of ZO-1,Occludin,and TFF3 in lung and colon tissues was increased after different treatments in UC rats.Notably,APS combined with matrine exerted a better protective effect against UC and lung injury compared with other treatments.CONCLUSION APS combined with matrine exert a synergistic protective effect against UC and lung injury,which might be associated with regulating TFF3 expression.

Desulfovibrio vulgaris,a potent acetic acid-producing bacterium,increased by Astragalus polysaccharides to attenuate nonalcoholic fatty liver disease in mice

OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

Influence of astragalus polysaccharide on kidney status and fibrosis indices of a ratmodel of streptozotocin-induced diabetic nephropathy

Object： To examine the effect of astragalus polysaccharide （APS） on kidney status and fibrosis indices of rats withdiabetic nephropathy. Methods： 72 male rats were randomly divided into three groups： negative control group （NC, n =24）; diabetic nephropathy model group （DNM, n = 24）; and diabetic nephropathy model with APS group （DNM ＋ APS,n = 24）. Rats of the DNM and DNM ＋ APS groups were subjected to both unilateral nephrectomy and administeredstreptozotocin （STZ） injection （65 mg/kg）. DNM ＋ APS group rats were administered 50 IU/kg/d APS by subcutaneousinjection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected withan identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group wererandomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day beforesacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats fromeach group were randomly selected to measure body weight and kidney index. Blood was collected to measure bloodglucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results：Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerularmesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induceddiabetic nephropathy rats treated with APS （50 IU/kg/d） showed significantly improved histological results, suggestingthat APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relievedrenal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reducedand the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.Conclusion： APS significantly improved renal tubular interstitial injury in DNM rats and the early stage of renalfunction damage. The mechanism may be related to downregulation of the expression of TGF-β1 and α-SMA whichdelays the progression of renal interstitial fibrosis in DNM rats.

Effects of Astragalus polysaccharide on immune function in B16 melanoma mice

Objective:To examine the effects of Astragalus polysaccharide on immune function in B16 melanoma mice.Method:Forty male C57BL/6 mice were divided equally into a control group,model group,Astragalus polysaccharide low-dose group,and Astragalus polysaccharide high-dose group,with 10 mice per group.B16 cells were used to develop a mouse model of melanoma.After B16 engraftment,40 mg/kg and 80 mg/kg Astragalus polysaccharide was administered by gavage every day to the Astragalus polysaccharide low-dose group and Astragalus polysaccharide high-dose group,respectively.Splenic index,thymic index,tumor growth curves,and tumor inhibition rates were measured.Flow cytometry was used to measure proportions of peripheral blood T lymphocyte subsets.Hematoxylin and eosin staining was used to examine histopathological changes in tumors.Immunofluorescence double staining was used to identify myeloid-derived suppressor cells in tumor tissues.Results:In the Astragalus polysaccharide high-dose group,splenic and thymic indices were significantly increased and tumor growth was inhibited in melanoma mice.Flow cytometry demonstrated increased CD4^(+)and CD4^(+)/CD8^(+)T-cell ratios in the high-dose Astragalus polysaccharide group.HE staining demonstrated significantly decreased numbers of tumor cells among mice with melanoma in the high-dose Astragalus polysaccharide group.Immunofluorescence double staining demonstrated significantly decreased numbers of myeloid-derived suppressor cells in tumor tissues in the high-dose Astragalus polysaccharide group.Conclusion:Astragalus polysaccharide inhibits tumor growth,increases splenic and thymic indices,increases CD4^(+)and CD4^(+)/CD8^(+)T-cell ratios,and decreases myeloid-derived suppressor cell numbers in melanoma mice.Our results indicate Astragalus polysaccharide may enhance immune function resulting in inhibition of tumorigenesis and tumor progression.

Extraction of Astragalus Polysaccharides and Ganoderma lucidum Mycelia Polysaccharides and Their in Vitro Antioxidative Effects

[Objectives]To explore the extraction and in vitro antioxidant effects of astragalus polysaccharides(APS)and Ganoderma lucidum mycelia polysaccharides(GLMPS).[Methods]By studying the polysaccharides of the herbal medicinal material Astragalus membranaceus and the fungal medicinal material Ganoderma lucidum mycelia,two polysaccharides were mixed according to different proportions and concentrations by using the principle of traditional Chinese medicine compound combination.The effect of polysaccharides on the scavenging ability of hydroxyl radical system was determined by salicylic acid method.[Results]When the compound ratios of GLMPS and APS were 1∶1,1∶4,1∶5,4∶1,and 5∶1,the scavenging effect of compound polysaccharides was better than that of single-component polysaccharides,and with the increase of concentration,the scavenging effect increased.When the ratio of GLMPS and APS was 5∶1,the hydroxyl radical scavenging rate of the compound polysaccharide reached 59.77%,which was 18.72%higher than that of single GLMPS and 28.58%higher than that of single APS.The scavenging effect of compound polysaccharide is closely related to the compound ratio and concentration.[Conclusions]APS and GLMPS can obtain better hydroxyl radical scavenging ability than single-component polysaccharides through compounding in appropriate proportions.In addition,within a suitable concentration range,as the concentration increases,the scavenging ability also increases.

Advances in anti-tumor mechanism and clinical application of Astragalus polysaccharides

Astragalus polysaccharide has the beneficial effect of Qi-deficiency,and it also has several anti-tumor mechanisms,including pharmacological actions and clinical functions.Through literature review,this work concluded anti-tumor mechanism and clinical application of astragalus polysaccharide,which was of considerable significance to expand and optimize its anti-tumor function and clinical application.

The related effects of astragalus polysaccharides on the improvement of bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer

Objective:To investigate the effects of astragalus polysaccharides(APS)on bone marrow suppression and hematopoietic stem cells during chemotherapy in elderly patients with lung cancer.Methods:120 elderly patients with lung cancer treated in the first hospital of Xingtai city from January 2019 to early December 2019 were divided into the treatment group and the control group by the random number table method,all of whom received pemetrexed+carboplatin chemotherapy,and the treatment group was treated with APS at the same time.The efficacy was evaluated after 2 cycles of chemotherapy,bone marrow suppression was observed,and levels of TCM symptoms score,peripheral blood T lymphocyte subgroup index,L-selectin(CD62L)and macrophage differentiation antigen-1(Mac-1)were measured before and after 2 cycles of chemotherapy.Results:The response rate(RR)was 56.67%in the treatment group and 45.00%in the control group,with no statistically significant difference(P>0.05);The disease control rate(DCR)in the treatment group was 81.67%,which was significantly higher than 65.00%in the control group(P<0.05);The reduction degree of leukopenia in the treatment group was significantly lower than that in the control group(P<0.05);The treatment group had a platelet reduction of grade 1+2 at a rate of 40.00%,and hemoglobin reduction of grade 1+2 at a rate of 28.33%,which were significantly lower than the control group at 65.00%and 58.33%(P<0.05);Compared with those before chemotherapy,the total score of TCM symptoms,serum CD62L and Mac-1 levels in the two groups all decreased significantly after chemotherapy,and they were significantly lower in the treatment group than in the control group(P<0.05);After chemotherapy,CD3+,CD4+and CD4+/CD8+in the treatment group increased significantly and they were all higher in the treatment group than in the control group,while CD8+decreased significantly and was lower in the treatment group than in the control group(P<0.05).There was no statistically significant difference in T lymphocyte subsets before and after chemotherapy in the control group(P>0.05).Conclusion:Astragalus polysaccharide can improve the chemotherapy effect and improve the bone marrow suppression in elderly patients with lung cancer,which may be related to its obvious enhancement of immune function and decrease of CD62L and Mac-1 levels.

Effects of astragalus polysaccharides on ventricular remodeling and miRNA-21 in rats with acute myocardial infarction

Objective:To investigate the effect of Astragalus polysaccharides(APS)on myocardial remodeling and expression of miR-21 after myocardial infarction.Methods:Sixty SPF grade healthy male rats were divided into the sham operation group,the model group,astragalus polysaccharide low,medium and high dose groups and atorvastatin group randomly with 10 rats in each group.The left anterior descending coronary artery(LAD)was ligated to establish myocardial infarction model in rats,and the corresponding drug intervention was given for 4 weeks.The changes of myocardial morphology and collagen were observed by HE and Masson staining.The levels of IL-1β,IL-6,TNF-αand IL-10 were detected by ELISA.The mRNA expressions of miR-21,MMP2,TIMP-2,Col-I,and Col-III was detected by RT-PCR.The protein expressions of TLR4,MyD88 and NF-κB p65 were detected by Western blot.Results:Compared with the model group,APS could improve the pathological morphology of myocardial tissue,increase the level of IL-10 in myocardial tissue,reduce the staining area of collagen and the contents of IL-1β,IL-6 and TNF-α(P<0.05).At the same time,APS could decreased the expression of MMP2,Col-I and Col-ⅢmRNA and the ratio of MMP2/TIMP-2,and increased the expression of TIMP-2 mRNA and miR-21 significantly(P<0.05).Furthermore,APS could significantly reduce the expression of TLR4,p-NF-κB p65 and MyD88 protein in myocardial tissue of rats with myocardial infarction,and the differences were statistically significant when compared with the model group(P<0.05).Conclusion:APS can inhibit the activation of TLR4/MyD88/NF-κB signaling pathway by upregulating the expression of miR-21,which plays a therapeutic role in ventricular remodeling after acute myocardial infarction.

Antitumor effect of combination treatment of Astragalus polysaccharide and PD-L1 antibody on mice with Lewis lung carcinoma

Objective:To investigate the antitumor effect of combination treatment of Astragalus polysaccharide and PD-L1 antibody on mice with Lewis lung carcinoma.Methods:Forty male C57BL/6 mice were selected and divided equally into Model group,PD-L1 group,APSgroup,and APS+PD-L1 group.Lewis lung carcinoma cells were used to establish the lung carcinoma mouse model.After successful modeling,the PD-L1 group was injected with 200μg of PD-L1 antibody intraperitoneally on day 0/4/8/12;the APS group was gavaged with 80 mg/kg of APS daily for 14 days;the APS+PD-L1 group was gavaged with 80 mg/kg of APS daily for 14 days,and in addition,200μg of PD-L1 antibody was injected intraperitoneally on day 0/4/8/12.The spleen and thymus indices of each group of mice were observed,to plot the tumor growth curve and calculate the tumor suppression rate.The ratio of T-lymphocyte subsets in peripheral blood was measured by flow cytometry;the level of T cell-related cytokines in peripheral blood was detected by ELISA;MTT assay was used to detect the tumor-killing function of spleen lymphocytes in vitro.Results:PD-L1,APS,and APS+PD-L1 groups significantly increased spleen and thymus indices and inhibited tumor growth in lung carcinoma mice;flow cytometry results showed that PD-L1,APS,and APS+PD-L1 groups increased CD4^(+)T-cell ratio and CD4^(+)/CD8^(+)T-cell ratio;ELISA results showed that PD-L1,APS,and APS+PD-L1 groups significantly increased T cell-associated cytokine levels;MTT results showed that PD-L1,APS,and APS+PD-L1 groups enhanced the tumor-killing function of splenic lymphocytes in vitro.Conclusions:Astragalus polysaccharide can inhibit tumor growth,increase spleen and thymus indices,increase CD4^(+)T-cell ratio and CD4^(+)/CD8^(+)T-cell ratio,aswell as improve T-cell-related cytokine levels and splenic lymphocyte tumor-killing function in vitro in a mouse model of lung carcinoma,essentially inhibiting tumorigenesis and progression.

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy:a novel delivery system candidate for tumor vaccines

The study of tumor nanovaccines(NVs)has gained interest because they specifically recognize and eliminate tumor cells.However,the poor recognition and internalization by dendritic cells(DCs)and insufficient immunogenicity restricted the vaccine efficacy.Herein,we extracted two molecular-weight Astragalus polysaccharides(APS,12.19 k D;APSHMw,135.67 k D)from Radix Astragali and made them self-assemble with OVA257–264directly forming OVA/APS integrated nanocomplexes through the microfluidic method.The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability.APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy.The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution.The FITC-OVA in APS-NVs could be effectively taken up by DCs,and APS-NVs could stimulate the maturation of DCs,improving the antigen cross-presentation efficiency in vitro.The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4.Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c.injection.Smaller APS-NVs could easily access the lymph nodes.Furthermore,APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells.In addition,APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group.The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region.Subsequently,the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs.Therefore,this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Background and Aims:Voriconazole(VRC),a widely used antifungal drug,often causes hepatotoxicity,which presents a significant clinical challenge.Previous studies demonstrated that Astragalus polysaccharide(APS)can regulate VRC metabolism,thereby potentially mitigating its hepatotoxic effects.In this study,we aimed to explore the mechanism by which APS regulates VRC metabolism.Methods:First,we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale.Second,we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism.Various in vitro and in vivo assays,including cytokine profiling,immunohistochemistry,quantitative polymerase chain reaction,metabolite analysis,and drug concentration measurements,were performed using a lipopolysaccharideinduced rat inflammation model.Finally,experiments such as intestinal biodiversity analysis,intestinal clearance assessments,and Bifidobacterium bifidum replenishment were performed to examine the ability of B.bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.Results:The results indicated that APS does not have a direct effect on hepatocytes.However,the assessment of gut microbiota function revealed that APS significantly increases the abundance of B.bifidum,which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism.The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway.Conclusions:The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage,highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Astragalus polysaccharide orβ-glucan combined with inactivated vaccine markedly prevent CyHV-2 infection in Carassius auratus gibelio

Herpesviral hematopoietic necrosis disease caused by cyprinid herpesvirus 2(CyHV-2)results in huge economic losses for the gibel carp(Carassius auratus gibelio)aquaculture industry.A vaccination strategy is a feasible method to prevent CyHV-2 infection and the resulting economic losses.In this study,inactivators(includingβ-propiolactone,formaldehyde and binary ethylenimine)were used to prepare an inactivated vaccine.The optimal inactivated CyHV-2 vaccine(0.2%β-propiolactone inactivates CyHV-2 for 48 h)mixed withβ-glucan,anisodamine,chitosan,and astragalus polysaccharide(APS)adjuvants were injected into gibel carp.Theβ-glucan and APS combined with inactivated vaccine significantly improved the relative immune protection rate of gibel carp against CyHV-2 infection.The highest specific antibody levels inβ-glucan and APS groups were found in serum by ELISA assay and antibody neutralization titer.Furthermore,adjuvant addition groups produced better results for lysozyme,total superoxide dismutase,and complement C3 in serum.β-glucan and APS combined with vaccine treatment effectively enhanced mRNA expressions of important immune genes(IL-1β,IgM,IL-2 and IFN-γ2).Minimal tissue lesions(gill,spleen,and head kidney)and virus replication were seen in theβ-glucan and APS groups by histopathological examination and expression analysis of CyHV-2 TK gene.These results indicated that the combination of inactivated vaccine and adjuvantβ-glucan or APS is an effective method against CyHV-2 infection and provided a case study reference for prevention of fish viral diseases using inactivated vaccines.

Inhibiting effect of Astragalus polysaccharides on the functions of CD4＋CD25^highTreg cells in the tumor microenvironment of human hepatocellular carcinoma

Background Astragalus polysaccharides （APS）, the main active extract from Astragalus membranaceus （a traditional Chinese medicinal herb）, is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma （HCC） and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4＋CD25^highTreq cells in tumor site of HCC.

Protective effects of emodin and astragalus polysaccharides on chronic hepatic injury in rats

Background Chinese medicine plays an important role in hepatoprotective treatment. This study was conducted to investigate the protective effects of emodin and astragalus polysaccharides （APS） in a rat model of chronic hepatic injury. Methods Chronic hepatic injury was induced by hypodermic injection of an olive oil solution containing 40% carbon tetrachlodde （CCI4） twice a week, in addition to a diet of 79.5% maizena, 20% fat, 0.5% cholesterol, and 10% alcohol in the drinking water ad libitum for 12 weeks. Meanwhile, the rats were exposed to different concentrations of emodin （40 mg·kg^-1·d^-1）, APS （200 mg·kg^-1·d^-1）, combination drug （emodin 40 mg·kg^-1·d^-1 combined with APS 200 mg·kg^-1·d^-1） and colchicine （0.1 mg·kg^-1·d^-1） in parallel by oral gavage （once a day for 12 weeks）. At the end of 12 weeks, blood serum and liver tissue were taken. Serum was collected to determine the levels of total bilirubin （TBIL）, alanine transaminase （ALT）, aspartate transaminose （AST）, and albumin （ALB）. Liver and spleen indexes were assayed, followed by the measurements of the liver associated enzyme superoxide dismutase （SOD） and malondialdehyde （MDA）. Histopathological changes were studied using optical microscopy. Results Splenohepatomegalia was alleviated and serum levels of TBIL and ALT were reduced in the groups treated with emodin and APS when compared to the control group. In addition, the ALB level in the APS and combination groups was higher. Similarly, the SOD activity of liver homogenates was significantly higher in the groups treated with emodin and APS, while administration of the herbal derivatives prevented the elevation in MDA levels. Histological analysis showed that the APS and combination groups significantly ameliorated the hepatic injury. Conclusions Co-administration of emodin and APS demonstrated a synergistic action in reducing ALT and restoring ALB in the serum from a rat model of chronic hepatic injury. Emodin and APS may ameliorate the CCI4-induced hepatic injury in rats by elevating antioxidant-enzyme activities and reducing lipid peroxidation.

Influence of Different Extraction and Purification Methods on Astragalus Polysaccharides and Pharmacological Evaluation

Objective To clarify the influence on component and pharmacological action of Astragalus polysaccharides(APS) as complementary therapeutic agents prepared by different extraction and purification techniques.Methods Components of APS prepared by different extraction and purification techniques were analyzed,and these APS were used for synergy and attenuation of chemotherapy,radiotherapy treatment with H22 liver cancer and Lewis lung cancer of tumor-bearing mice,and also used for the regulation of immune function to immunosuppression mice.Results Experimental data were analyzed by means of statistical method to get pharmaco-result:A3(extracted by microwave assistance and purified by membrane separation)>A4(extracted by refluxing and purified by membrane separation)>A1(extracted by refluxing and no purification)≈A2(extracted by microwave assistance and no purification).There were no significant differences on pharmacodynamic action between A1 and A2.However,compared with A1 and A2,it was worth noting that A3 and A4 exhibited good pharmacodynamic action.Then A3-in and A4-in,the samples in dialyzer after dialysis,were separated and purified to get homogeneous APS,which were the principal constituents of APS in dialyzer,with the molecular weight(Mw) of 7669 and 14142 determined by HPGPC,respectively.The average Mw of APS outside of the dialyzer,A3-out was 3102 and A4-out 3256,which were the main compositions of A3 and A4,accounted for 79.63% and 53.92%,respectively.Conclusion APS with Mw about 5000 Da exhibit better antitumor effect and immunological activity.Refluxing,microwave assistance extractions,and membrane enrichment techniques bring different cases on Mw distribution,components and pharmacodynamic action,and obviously exhibit relationship among component,Mw distribution,and pharmacological action.

Angiogenesis effect of Astragalus polysaccharide combined with endothelial progenitor cells therapy in diabetic male rat following experimental hind limb ischemia

Background Diabetes mellitus （DM） is a common disease accompanied with a high incidence of hind limb ischemia （HLI）.In recent years,numerous studies demonstrated that endothelial progenitor cells （EPCs） are involved in angiogenesis and maintenance of vascular integrity following HLI.On the other side,it has been proved that Astragalus polysaccharide （APS） could promote angiogenesis.In the present study,we aimed to evaluate the effect of APS and EPCs on enhancing angiogenesis after experimental HLI caused by femoral artery ligation in rats with streptozotocin （STZ）-induced diabetes.Methods Rats （n=110） were randomly assigned to the following groups：sham group,ischemia group,APS group,EPCs group and APS＋EPCs group.APS,EPCs or an equal volume of vehicle was administered intramuscularly after HLI induction,and 6 rats were assessed by angiography at 28 days after induction of HLI,6 rats were sacrificed at the same time point to take histological studies,biochemical tests were also performed at that point in the rest rats.Results APS or EPCs treatment induced an increase,respectively,in the protein expression of vascular endothelial growth factor （VEGF） （36.61%,61.59%）,VEGF receptor-1 （VEGFR-1） （35.50%,57.33%）,VEGFR-2 （31.75%,41.89%）,Angiopoietin-1 （Ang-1） （37.57%,64.66%） and Tie-2 （42.55%,76.94%） （P 〈0.05）,after HLI injury.And combined therapy of APS and EPCs enhanced the effort of angiogenesis after HLI induction in diabetic rats,through elevating protein expression of VEGF （99.67%）,VEGFR-1 （105.33%）,VEGFR2 （72.05%）,Ang-1 （114.30%） and Tie-2 （111.87%） （P〈0.05）.Similarly,mRNA expression of VEGF,VEGFR-1,VEGFR2,Ang-1,Tie-2 also show similar trends as well as protein expression （P〈0.05）.Conclusion APS or EPCs could enhance angiogenesis,and the combined treatment leads to better effort,at least,partially via VEGFNEGFR and Ang-1/Tie-2 signaling pathway.