|Year : 2020 | Volume
| Issue : 3 | Page : 99-104
Immuno-potentiating effects of Astragalus polysaccharides: A mini-literature review
Hung- Chih Lai1, Jo- Pai Chen2
1 Department of Hematology and Oncology, Shin-Kong Wu Ho.Su Memorial Hospital, Taipei, Taiwan
2 Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
|Date of Submission||08-Aug-2019|
|Date of Decision||21-Jan-2020|
|Date of Acceptance||11-Feb-2020|
|Date of Web Publication||1-Sep-2020|
Dr. Jo- Pai Chen
Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, No. 95, Xuefu Rd., Huwei Township, Yunlin 632
Source of Support: None, Conflict of Interest: None
Objective: Astragalus polysaccharides (APS) is a promising therapeutic agent because of its long history in ethnopharmacology, extensive research, wide application, and few side effects. Among its diversified properties, APS has been widely investigated for its immuno-potentiating effects such as stimulating T- and B-cell proliferation, regulating the expression of cytokines, activating macrophages, inducing the expression of surface antigens on lymphocytes, and promoting the production of antibodies. Data Sources: In this article, we review the research progress of APS focusing on its immuno-potentiating effects. Results: Based on the existing studies, APS appears to be a promising adjuvant to anticancer therapy, vaccines, antibiotics, and antiviral therapy. The information provided in this mini-review will provide a useful quick reference for its rational clinical utilization and in planning further research. Further studies are needed to evaluate its dose optimization, mechanism of action, and therapeutic combination strategies. Conclusion: APS may be another successful example of the standardization and modernization of Traditional Chinese herbal medicine.
Keywords: Adjuvant anti-tumor, Astragalus membranaceus, Astragalus polysaccharides, Astragalus, cytokines, immunomodulation, immunopotentiation, T-cells
|How to cite this article:|
Lai HC, Chen JP. Immuno-potentiating effects of Astragalus polysaccharides: A mini-literature review. J Cancer Res Pract 2020;7:99-104
|How to cite this URL:|
Lai HC, Chen JP. Immuno-potentiating effects of Astragalus polysaccharides: A mini-literature review. J Cancer Res Pract [serial online] 2020 [cited 2020 Oct 1];7:99-104. Available from: http://www.ejcrp.org/text.asp?2020/7/3/99/294019
| Introduction|| |
Astragalus species has a long history of use in Traditional Chinese medicine.Astragalus polysaccharides (APS) is the main active extract of Astragalusmembranaceus (also known as Radix Astragali or Huangqi). APS is a well-tolerated therapeutic agent and is approved as an injectable Class II Chinese herb. It is comprised polysaccharides, including mannose, D-glucose, D-galactose, xylose, and L-arabinose and glycoproteins. It exhibits a variety of bioactivities including antioxidant, immunomodulatory, anti-tumor, anti-inflammatory, and antiviral activities.,, APS is promising because of its long history in ethnopharmacology, extensive research, wide application, and few side effects.
A few studies have indicated that APS can alter the composition of breast milk, and thus, its use should be avoided in pregnant and nursing women. Tan et al. reported in a preclinical study that dietary supplementation of APS significantly enhanced the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), epidermal growth factor, and insulin-like growth factor-1 in 0 h-colostrum (P < 0.001), and the blocking rates of classical swine fever virus antibody were increased. APS also has galactogog properties; however, no scientifically valid clinical trials support this clinical use. Finally, since dietary supplements do not require extensive premarketing approval from the U. S. Food and Drug Administration and manufacturers do not need to strictly prove the safety and effectiveness of dietary supplements before they are marketed, such dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. This warrants caution with regard to its use in pregnant and nursing women.
Among its diverse properties, APS has been widely investigated for its immuno-potentiating effects such as stimulating T- and B-cell proliferation, regulating the expression of cytokines, activating macrophages, inducing the expression of surface antigens on lymphocytes, and promoting the production of antibodies. In this article, we review the research progress of APS, focusing on its immuno-potentiating effects. This information will provide a useful reference for its rational clinical utilization and in planning further research.
| Cytokine Expression|| |
The immuno-potentiating effects of APS are largely attributable to regulating the production of cytokines. APS upregulates the production of cytokines interleukin (IL)-1α, IL-1 β, IL-2, IL-3, IL-6, tissue necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), fas ligand (FasL) and GrB, immunoglobulins including IgM, IgG, immunoglobulin A, and growth factors including granulocyte monocyte colony-stimulating factor. This APS-induced upregulation has been shown to be dose-dependent for cytokines IL-1 β, TNF-α, and lysozyme-C. It has been shown to inhibit CD4+ CD25+ Foxp3+ T regulatory (Treg) cells in liver cancer patients, IL-10, stromal cell-derived factor 1 in human hepatocellular carcinoma (HCC) cells, and immunoglobulin IgE. Overall, APS can restore the cytokine balance in the tumor microenvironment. It has also been shown to have synergistic anti-tumor effects with doxorubicin in inducing cell death in HL-60 cells. Further, by modulating cytokine release, APS has been shown to inhibit tumor cell growth in Kunming mice with Ehrlich's ascites carcinoma, in rats with gastric cancer, improve the activity of intraepithelial γδT cells in tumor-bearing mice, and to have a synergistic anti-tumor effect with chemotherapy. Owing to its cytokine modulating properties, APS has been shown in preclinical studies (in vivo and in vitro) to inhibit viral replication, act as an adjuvant to anti-viral vaccines, and enhance the immune response in liver inflammatory conditions such as chronic hepatitis, cirrhosis, and liver cancer.
Astragalus polysaccharide (PG2) injection is an approved drug in Taiwan for cancer-related fatigue (CRF). CRF has been reported to be the most frequent and debilitating symptom in 60%–90% of cancer patients. It is a systemic disease, potentially resulting from many underlying mechanisms. Further fatigue and depression may co-exist and show an overlap of symptoms. The impact of APS on cytokine profile and thereby CRF is still under investigation.
Yeh and Wang reported thatin vivo injections of A. membranaceus can suppress the proliferation and differentiation of autoreactive T-cells by elevating Treg IL-10 and reducing IL-6. It has also been shown to further regulate the effects of Thl/Th2 imbalance and secreted cytokines as well as promote the phenotypic and functional maturation of dendritic cells. In another study, APS was reported to regulate the inflammatory response by reducing TNFα secretion in Caco2 cells. However, high dose APS may increase the Th17 cell population, which is known to promote the production and secretion of proinflammatory cytokines. This is an interesting finding, and further studies are required to clarify the mechanism of APS in relieving CRF. Another example of the dose-dependent contradictory effect of APS was observed in a study by Chen et al. which evaluated the impact of different doses of APS on the functional status and phenotype of T-cells during polymicrobial sepsis. They observed that lower doses of APS (100 or 200 mg/kg body weight) downregulated the percentages of circulating Th2 cells and Treg cells, and that the percentage of Th17 cells in blood was upregulated in the group receiving a high dose of APS of 400 mg/kg body weight.
Clinically, APS has also been proven to be a complementary and palliative medicine for treating CRF. In a randomized, double-blind, placebo-controlled trial, PG2 administration resulted in greater improvements in fatigue-improvement response rates, enhanced mood, and enjoyment of life for cancer patients. Therefore, PG2 is the first fatigue modulator to relieve fatigue-related psychosocial distress with minimal adverse risks compared with normal saline injections. Among the varied mix of cancer patients included in the study, breast cancer patients benefitted the most from PG2 treatment. Wang et al. conducted the first large-scale randomized clinical trial to study the efficacy and safety of pharmacological treatment for CRF with over 300 advanced cancer patients enrolled. They demonstrated that PG2 injection could effectively relieve fatigue in advanced cancer patients.
| Regulating Gene Expression in Tumor Cells|| |
APS has been shown to inhibit the gene expression of notch1 and notch3 in nonsmall-cell lung cancer (NSCLC), CD44 in mice with Lewis lung carcinoma, p65, p50, NF-κB, CyclinD1 and Bcl-xL protein in A549 and NCI-H358 cells, FOXP3 in human HCC cells, the NF-κ B pathway in porcine circovirus type 2 (PCV2) and multi-drug-resistant 1 mRNA, Bcl-2 and P-glycoprotein (MRP1)-efflux pump in H22/ADM hepatoma cells. Gene upregulating effects of APS have been reported in p53, p21, p16, Bax, and caspase-8 of NSCLC, in p53 and PTEN of breast cancer cell line MDA-MB-468, and in Bax/Bcl-2 ratio and caspase of nasopharyngeal carcinoma cell lines, xenograft model and hepatoma cells. APS has been shown to regulate pathways such as p53/murine double minute 2 positive and negative feedback loops in MDA-MB-468 breast cancer cells, Toll-like receptor 4 (TLR4)-mediated MyD88-dependent signaling pathway in macrophage RAW 264.7 and EAC tumor-bearing mice owing to these mechanisms, APS has dose-dependent anti-proliferative and apoptotic effects on tumors and exhibits chemosensitization effects. Wu et al. were the first to report the antitumor activity of APS in human NSCLC cells independently of the immunomodulatory effects.
There are some clinical data to support the efficacy and safety of APS in various malignancies. Duan and Wang observed the effect of intravenous APS on enhancing chemotherapy and reducing the toxicity in 120 patients with various malignant tumors. The treated group had a lower progressive incidence, lesser decrease in peripheral white blood cell, and platelet count (P < 0.05), accompanied with a significant decrease in CD8 (P < 0.05), significant increase in CD4/CD8 ratio (P < 0.01), and significant increases in IgG and IgM levels (P < 0.05) and Karnofsky scores elevated compared to the control group. Another meta-analysis of 22 studies including 1409 patients indicated that the combination of Astragalus-based Chinese medicines and chemotherapy may increase the efficiency of tumor response rate for the treatment of colorectal cancer patients, improve their life quality based on Karnofsky Performance Status (KPS), and reduce adverse reactions including neutropenia, anemia, thrombocytopenia, nausea, vomiting, and neurotoxicity. Another meta-analysis from Wang et al. showed that Astragalus-containing Chinese herbal formulae plus platinum-based chemotherapy was more effective than platinum-based chemotherapy alone in patients with NSCLC. These findings were further validated by Cao et al.
| Dendritic Cells and T Cell Polarization|| |
APS induces the differentiation and maturation of dendritic cells (DCs) and enhances their antigen-presenting ability., Similarly,in vitro studies have shown that APS induces the differentiation of splenic DCs to IL-12-producing CD11chigh CD45RBlow DCs, and further mediates the activation of immune function of CD4+ T-cells with shifting of Th2 to Th1. It is noteworthy that this effect was not associated with the inhibition of IL-10 production in CD11c (low) CD45RB (high) DCs. APS has been shown to inhibit Th2 polarization, enhance the gene expression of Th1 cytokines (IFN-γ and IL-2) and its transcript factor (T-bet) and reduce those of Th2 cytokines, and increase CD4(+)/CD8(+) T cell ratio in lung cancer and Aeromonas hydrophila-infected mice. Thus, APS reverses Th2 polarization-induced immunosuppression and has potential clinical application in conditions with an imbalance in Th1/Th2 cytokine ratios such as tumors, thermal injury, and bacterial infections.
| Natural Killer Cell|| |
Natural killer cells (NK cells) are an important component in the antiviral immune response and are typically activated in response to IL-2, IL-12, IL-15, IL-18, and CCL5. After being treated with APS 15 mg/ml for 48 h, the cytotoxicity of NK cells against leukemic cell line HL-60 cells was shown to be enhanced at different effect-to-target, and the gene and protein expressions in major histocompatibility complex (MHC) Class I chain-related HL-60 cells were upregulated. A study conducted in 1992 by Zhao evaluating the effects of A. membranaceus and Tripterygium hypoglancum on NK cell activity of peripheral blood mononuclear cells in patients with systemic lupus erythematosus showed that preincubation with APS considerably stimulated NK cytotoxicity both in systemic lupus erythematosus patients and healthy donors. However, no recent study has evaluated this combination.
| T Regulatory Cells|| |
APS has been shown to bind to TLR4 on Tregs, decrease the expression of Foxp3, inhibit CD4(+) CD25(+) Tregs, and resolve infection-induced immunosuppression in burned mice with Pseudomonas aeruginosa infection. Indeed, anti-TLR4 antibodies can block the effect of APS on Treg cell immune function. However, high-dose APS (400 mg APS/kg) may excessively repress Treg response and cause excessive polarization toward the proinflammatory Th1 and Th17 lineages and may aggravate sepsis-induced organ injury., At a dose of 100 and 200 mg APS/kg, APS has been shown to reduce the number of Treg cells, elicit a balanced Th1/Th2 response, and further attenuate immunosuppression in polymicrobial sepsis. Hence, dose optimization is warranted.
| Macrophages|| |
APS stimulates macrophage activity by triggering TLR4-mediated signaling pathways which upregulate the expressions of p-p38, p-ERK, and p-JNK, induce IκB-α degradation and NF-κB translocation, then finally enhance the production of TNF-α, IL-6, and nitric oxide. Hence, APS has high clinical potential in the management of infection caused by bacteria, including Mycobacterium tuberculosis, viruses, or fungi such as Candida albicans., APS demonstrates an interesting dose-response relationship with macrophage phagocytotic activity, wherein phagocytosis is initially enhanced, but with further increases in the dose, high levels of cytokines are produced which downregulates phagocytic function. This again implies the need for dose-optimization studies, particularly in sepsis.
| Toll-Like Receptors|| |
APS can induce the TLR4 expression in bladder epithelial cellsin vivo and in vitro, thereby enhancing innate immune response. This finding establishes the use of APS as an alternative option for urinary tract infection treatment. Similarly, APS has been shown to increase immune organ indexes through the activation of the TLR4-mediated MyD88-dependent signaling pathway, thereby reducing tumor weight in EAC breast tumor-bearing mice. However, APS has also been shown to activate B-lymphocytes through membrane Ig in a TLR4-independent manner.
| Potential Immune Adjuvant To Vaccines|| |
APS as an adjuvant has been shown to improve the immunogenicity of hepatitis B virus subunit vaccines through humoral and cellular immune responses, affect the TLR4 signaling pathway, inhibit negative regulators such as transforming growth factor-beta (TGF-β) and Treg cells, produce a high level of cytotoxic T lymphocyte (CTL) response and increase IFN-γ production in CD8+ T cells and IFN-γ, IL-2, and production in CD4+ T-cells, and upregulate the expressions of, Gra B, FasL, and Fas in CD8+ T cells. It has also been shown to lead to the dose-dependent upregulation of serum anti-IBV antibody titers in response to IBV vaccination. In anin vivo model of immunization with foot-and-mouth disease virus vaccine, APS could upregulate both cellular and humoral immune responses. Similarly, APS could resist the immunosuppression in a chicken model induced with cyclophosphamide by promoting T-lymphocyte proliferation and raising the serum levels of antibody titers. Moreover, in chickens infected with Newcastle disease, APS liposome was shown to promote lymphocyte proliferation and enhance antibody titers. APS may also have the potential to be an effective component in vaccines against classical swine fever virus (CSFV) by inhibiting increases in TF, TGF-β, and IL-8 and inhibiting the upregulation of TLR4 in porcine endothelial cells caused by CSFV.
| General Anti-Oxidant Effects|| |
APS reduces reactive oxygen species and endoplasmic reticulum stress, and thus exhibits antioxidant activity. This function has been observed in PCV2 infection in vitro and A. hydrophila-infected micein vivo. Related to this, an improvement in the quality of life has been observed with APS administration in patients with advanced NSCLC, respiratory system tumors, and gastric tumors. Further, in patients with advanced NSCLC, APS injection with vinorelbine and cisplatin has been shown to reduce fatigue, nausea, vomiting, pain, and loss of appetite. Similar benefits have been achieved in combination with radiotherapy in esophageal cancer.
A summary of the immune-potentiating effects of APS is depicted in [Figure 1] and [Figure 2].
|Figure 1: Pathways and activated downstream proteins or cells affected by Astragalus polysaccharides|
Click here to view
|Figure 2: Summary of the immuno-potentiating effects of Astragalus polysaccharides|
Click here to view
| Conclusion|| |
Based on the existing studies, APS appears to be a promising adjuvant to anti-cancer therapy, vaccines, antibiotics, and anti-viral therapy. It may be another successful example of the standardization and modernization of traditional Chinese herbal medicine. Further studies are needed to evaluate the dose optimization, mechanism of action, and therapeutic combination strategies. Caution must be taken in patients who are on immunosuppressive drugs, in pregnant and nursing women, and in patients with immune system disorders.
The authors would like to acknowledge the medical writing support provided by Dr. Pratishtha Banga from WriterMD Medical Writing Consultancy. They would also like to acknowledge the funding of medical writing provided by Phytohealth Corporation. The funding organization had no role in the preparation of the manuscript or interpretation of data.
Financial support and sponsorship
The medical writing of this paper was funded by Phytohealth Corporation.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tian QE, Li HD, Yan M, Cai HL, Tan QY, Zhang WY. Astragalus
polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice. World J Gastroenterol 2012;18:7079-86.
Luo Z, Zhong L, Han X, Wang H, Zhong J, Xuan Z. Astragalus
membranaceus prevents daunorubicin-induced apoptosis of cultured neonatal cardiomyocytes: Role of free radical effect of Astragalus
membranaceus on daunorubicin cardiotoxicity. Phytother Res 2009;23:761-7.
Fu J, Wang Z, Huang L, Zheng S, Wang D, Chen S, et al
. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus
membranaceus (Huangqi). Phytother Res 2014;28:1275-83.
Jiang J, Wu C, Gao H, Song J, Li H. Effects of Astragalus
polysaccharides on immunologic function of erythrocyte in chickens infected with infectious bursa disease virus. Vaccine 2010;28:5614-6.
Jiang JB, Qiu JD, Yang LH, He JP, Smith GW, Li HQ. Therapeutic effects of Astragalus
polysaccharides on inflammation and synovial apoptosis in rats with adjuvant-induced arthritis. Int J Rheum Dis 2010;13:396-405.
Li R, Chen WC, Wang WP, Tian WY, Zhang XG. Antioxidant activity of Astragalus
polysaccharides and antitumour activity of the polysaccharides and siRNA. Carbohydr Polym 2010;82:240-4.
Liu P, Zhao H, Luo Y. Anti-aging implications Astragalus
membranaceus (huangqi): A well-known Chinese tonic. Aging Dis 2017;8:868-86.
Tan L, Wei T, Yuan A, He J, Liu J, Xu D, et al
. Dietary supplementation of Astragalus
polysaccharides enhanced immune components and growth factors EGF and IGF-1 in sow colostrum. J Immunol Res 2017;2017, Article ID 9253208.
Scott CR, Jacobson H. A selection of international nutritional and herbal remedies for breastfeeding concerns. Midwifery Today Int Midwife 2005;75:38-9.
Kallon S, Li X, Ji J, Chen C, Xi Q, Chang S, et al
polysaccharide enhances immunity and inhibits H9N2 avian influenza virusin vitro
and in vivo
. J Anim Sci Biotechnol 2013;4:22.
Yuan C, Pan X, Gong Y, Xia A, Wu G, Tang J, et al
. Effects of Astragalus
polysaccharides (APS) on the expression of immune response genes in head kidney, gill and spleen of the common carp, Cyprinus carpio
L. Int Immunopharmacol 2008;8:51-8.
Li Q, Bao JM, Li XL, Zhang T, Shen XH. Inhibiting effect of Astragalus
polysaccharides on the functions of CD4+CD25 highTreg cells in the tumor microenvironment of human hepatocellular carcinoma. Chin Med J (Engl) 2012;125:786-93.
Kuo YL, Chen CH, Chuang TH, Hua WK, Lin WJ, Hsu WH, et al
. Gene expression profiling and pathway network analysis predicts a novel antitumor function for a botanical-derived drug, PG2. Evid Based Complement Alternat Med 2015;2015, Article ID 917345.
Li J, Bao Y, Lam W, Li W, Lu F, Zhu X, et al
. Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus
polysaccharides on tumor-bearing mice. Immunopharmacol Immunotoxicol 2008;30:771-82.
Sun S, Zheng K, Zhao H, Lu C, Liu B, Yu C, et al
. Regulatory effect of Astragalus
polysaccharides on intestinal intraepithelial γδT cells of tumor bearing mice. Molecules 2014;19:15224-36.
Du X, Chen X, Zhao B, Lv Y, Zhang H, Liu H, et al
polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor β and the frequency of regulatory T cells. FEMS Immunol Med Microbiol 2011;63:228-35.
Yeh CT, Wang LS. Potential pathophysiological mechanism of cancer-related fatigue and current management. Formos J Surg 2014;47:173-82.
Wang X, Li Y, Yang X, Yao J. Astragalus
polysaccharide reduces inflammatory response by decreasing permeability of LPS-infected Caco2 cells. Int J Biol Macromol 2013;61:347-52.
Hou YC, Wu JM, Wang MY, Wu MH, Chen KY, Yeh SL, et al
. Modulatory effects of Astragalus polysaccharides on T-cell polarization in mice with polymicrobial sepsis. Mediators Inflamm 2015;2015, Article ID 826319.
Chen HW, Lin IH, Chen YJ, Chang KH, Wu MH, Su WH, et al
. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: A phase II double-blind, randomized placebo-controlled study. Clin Invest Med 2012;35:E1-11.
Wang CH, Lin CY, Chen JS, Ho CL, Rau KM, Tsai JT, et al
. Karnofsky performance status as a predictive factor for cancer-related fatigue treatment with Astragalus
polysaccharides (PG2) injection-a double blind, multi-center, randomized phase iv study. Cancers (Basel) 2019;11:128.
Zhang JX, Han YP, Bai C, Li Q. Notch1/3 and p53/p21 are a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines. Int J Clin Exp Med 2015;8:12539-47.
Ming H, Chen Y, Zhang F, Wang Q, Dong X, Gu J, et al
polysaccharides combined with cisplatin decreases the serum levels of CD44 and collagen type IV and hyaluronic acid in mice bearing Lewis lung cancer. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2015;31:909-13.
Wu CY, Ke Y, Zeng YF, Zhang YW, Yu HJ. Anticancer activity of Astragalus
polysaccharide in human non-small cell lung cancer cells. Cancer Cell Int 2017;17:115.
Xue H, Gan F, Zhang Z, Hu J, Chen X, Huang K. Astragalus
polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway. Int J Biol Macromol 2015;81:22-30.
Tian QE, De Li H, Yan M, Cai HL, Tan QY, Zhang WY. Effects of Astragalus
polysaccharides on P-glycoprotein efflux pump function and protein expression in H22 hepatoma cells in vitro
. BMC Complement Altern Med 2012;12:94.
Ye MN, Chen HF, Zhou RJ, Liao MJ. Effects of Astragalus
polysaccharide on proliferation and Akt phosphorylation of the basal-like breast cancer cell line. Zhong Xi Yi Jie He Xue Bao 2011;9:1339-46.
Zhou Z, Meng M, Ni H. Chemosensitizing effect of Astragalus
polysaccharides on nasopharyngeal carcinoma cells by inducing apoptosis and modulating expression of Bax/Bcl-2 ratio and caspases. Med Sci Monit 2017;23:462-9.
Zhou L, Liu Z, Wang Z, Yu S, Long T, Zhou X, et al
. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro
and in vivo
. Sci Rep 2017;7:44822.
Duan P, Wang ZM. Clinical study on effect of Astragalus
in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002;22:515-7.
Wang SF, Wang Q, Jiao LJ, Huang YL, Garfield D, Zhang J, et al
-containing traditional Chinese medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: A systemic review and meta-analysis. Curr Oncol 2016;23:e188-95.
Cao A, He H, Wang Q, Li L, An Y, Zhou X. Evidence of Astragalus
injection combined platinum-based chemotherapy in advanced nonsmall cell lung cancer patients: A systematic review and meta-analysis. Medicine (Baltimore) 2019;98:e14798.
Shao P, Zhao LH, Zhi-Chen, Pan JP. Regulation on maturation and function of dendritic cells by Astragalus
mongholicus polysaccharides. Int Immunopharmacol 2006;6:1161-6.
Liu QY, Yao YM, Zhang SW, Sheng ZY. Astragalus
polysaccharides regulate T cell-mediated immunity via CD11c(high)CD45RB(low) DCs in vitro
. J Ethnopharmacol 2011;136:457-64.
Wei H, Sun R, Xiao W, Feng J, Zhen C, Xu X, et al
. Traditional Chinese medicine Astragalus
reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients. Oncol Rep 2003;10:1507-12.
Abuelsaad AS. Supplementation with Astragalus
polysaccharides alters aeromonas-induced tissue-specific cellular immune response. Microb Pathog 2014;66:48-56.
Zeng PY, Deng LL, Yue LL, Zhang LS. Effect of Astragalus
polysaccharide on sensitivity of leukemic cell line HL-60 to NK cell cytotoxicity and its mechanism. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2012;20:880-3.
Zhao XZ. Effects of Astragalus
membranaceus and Tripterygium
hypoglancum on natural killer cell activity of peripheral blood mononuclear in systemic lupus erythematosus. Zhongguo Zhong Xi Yi Jie He Za Zhi 1992;12:669-71, 645.
Liu QY, Yao YM, Yu Y, Dong N, Sheng ZY. Astragalus
polysaccharides attenuate postburn sepsis via inhibiting negative immunoregulation of CD4+ CD25(high) T cells. PLoS One 2011;6:e19811.
Paust HJ, Turner JE, Steinmetz OM, Peters A, Heymann F, Hölscher C, et al
. The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. J Am Soc Nephrol 2009;20:969-79.
Shao BM, Xu W, Dai H, Tu P, Li Z, Gao XM. A study on the immune receptors for polysaccharides from the roots of Astragalus
membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun 2004;320:1103-11.
Xu HD, You CG, Zhang RL, Gao P, Wang ZR. Effects of Astragalus
polysaccharides and astragalosides on the phagocytosis of Mycobacterium tuberculosis
by macrophages. J Int Med Res 2007;35:84-90.
Akira S, Takeda K, Kaisho T. Toll-like receptors: Critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-80.
Yin X, Chen L, Liu Y, Yang J, Ma C, Yao Z, et al
. Enhancement of the innate immune response of bladder epithelial cells by Astragalus
polysaccharides through upregulation of TLR4 expression. Biochem Biophys Res Commun 2010;397:232-8.
Zhang N, Li J, Cheng G, Zhu X, Liu F, Zhang Y, et al
. Effects of Astragalus
polysaccharide on the immune response to foot-and-mouth disease vaccine in mice. Carbohyd Polym 2010;82:680-6.
Guo L, Liu J, Hu Y, Wang D, Li Z, Zhang J, et al
polysaccharide and sulfated epimedium polysaccharide synergistically resist the immunosuppression. Carbohydr Polym 2012;90:1055-60.
Fan Y, Hu Y, Wang D, Liu J, Zhang J, Zhao X, et al.
Effects of Astragalus
polysaccharide liposome on lymphocyte proliferation in vitro
and adjuvanticity in vivo
. Carbohyd Polym 2012;88:68-74.
Zhuge Z, Dong Y, Li L, Jin T. Effects of Astragalus
polysaccharide on the adhesion-related immune response of endothelial cells stimulated with CSFV in vitro
. PeerJ 2017;5:e3862.
Xue H, Gan F, Qian G, Hu J, Hao S, Xu J, et al
polysaccharides attenuate PCV2 infection by inhibiting endoplasmic reticulum stressin vivo
and in vitro
. Sci Rep 2017;7:40440.
Guo L, Bai SP, Zhao L, Wang XH. Astragalus
polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: Effects on quality of life and survival. Med Oncol 2012;29:1656-62.
Wang JC, Tian JH, Ge L, Gan YH, Yang KH. Which is the best Chinese herb injection based on the FOLFOX regimen for gastric cancer? A network meta- analysis of randomized controlled trials. Asian Pac J Cancer Prev 2014;15:4795-800.
Ge L, Mao L, Tian JH, Shi FY, Lou Li-li, Qiu X, et al
. Network meta-analysis on selecting Chinese medical injections in radiotherapy for esophageal cancer. Zhongguo Zhong Yao Za Zhi 2015;40:3674-81.
[Figure 1], [Figure 2]