Immunomodulatory Effects of Astragaloside and Other Triterpenoid Saponins: Advances and Mechanistic Insights
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v7i1.4905
Abstract
Astragalus membranaceus, a treasured herb in traditional Chinese medicine, has garnered extensive attention for its immunomodulatory properties in both clinical and experimental settings. Among its bioactive constituents, triterpenoid saponins such as astragaloside are recognized as the principal agents underlying its therapeutic efficacy. This review systematically summarizes the current research progress on the immunoregulatory effects of astragaloside and related triterpenoid saponins derived from Astragalus. We begin by outlining the historical and pharmacological background of Astragalus and its key active components. Subsequently, the review delves into the modulation of innate and adaptive immune responses by astragaloside, highlighting the molecular mechanisms and signaling pathways involved. Additionally, recent pharmacological findings and potential clinical applications are discussed to provide a comprehensive understanding of these compounds’ roles in immune regulation. This synthesis aims to offer a theoretical framework to guide future investigations and the development of Astragalus-based immunotherapeutics.
Keywords
Astragalus; astragaloside; triterpenoid saponins; immunomodulation; innate immunity; adaptive immunity
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[2] Zhang J, Wu C, Gao L, Du G, Qin X. Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects. Adv Pharmacol. 87:89-112. doi:10.1016/bs.apha.2019.08.002 https://pubmed.ncbi.nlm.nih.gov/32089240/
[3] Lin C, Liu H, Dong S, et al. Beyond Traditional Use: The Scientific Evidence for the Role of Astragali radix in Organ Protection via Modulating Oxidative Stress, Cell Death, and Immune Responses. Pharmaceuticals (Basel). 2025;18(10). Published 2025 Sep 26. doi:10.3390/ph18101448 https://pubmed.ncbi.nlm.nih.gov/41155562/
[4] Xu L, Li Y, He Z, Chen W, Li Y. Astragaloside IV ameliorates experimental autoimmune myasthenia gravis through multi-target regulation of immune-microbiota-metabolism network and ferroptosis inhibition. Pathol Res Pract. 282:156423. Published online Feb 24,2026. doi:10.1016/j.prp.2026.156423 https://pubmed.ncbi.nlm.nih.gov/41795502/
[5] Yang L, Han X, Yuan J, et al. Early astragaloside IV administration attenuates experimental autoimmune encephalomyelitis in mice by suppressing the maturation and function of dendritic cells. Life Sci. 249:117448. doi:10.1016/j.lfs.2020.117448 https://pubmed.ncbi.nlm.nih.gov/32087232/
[6] Wang D, Cui Q, Yang YJ, Liu AQ, Zhang G, Yu JC. Application of dendritic cells in tumor immunotherapy and progress in the mechanism of anti-tumor effect of Astragalus polysaccharide (APS) modulating dendritic cells: a review. Biomed Pharmacother. 155:113541. doi:10.1016/j.biopha.2022.113541 https://pubmed.ncbi.nlm.nih.gov/36127221/
[7] Zhao C, Yang X, Yao M, Song X, Dai J, He P. Cycloastragenol in inflammation-related diseases: mechanisms, pharmacokinetics, and translational prospects. Front Pharmacol. 16:1732996. Published 2025 None. doi:10.3389/fphar.2025.1732996 https://pubmed.ncbi.nlm.nih.gov/41601951/
[8] Yang L, Huang H, Fan Y, et al. Astragaloside IV ameliorates Parkinson’s disease by inhibiting TLR4/NF-κB-dependent neuroinflammation. Int Immunopharmacol. 160:114972. doi:10.1016/j.intimp.2025.114972 https://pubmed.ncbi.nlm.nih.gov/40449268/
[9] Liu Y, An T, Que Z, et al. Inhalable Herbal Nano-Liposomes Co-Delivering Astragaloside IV and Polyphyllin VII Reprogram Immunosuppressive Microenvironment To Overcome Anti-PD-1 Resistance in NSCLC. Biol Proced Online. 2025;27(1):43. Published 2025 Nov 10. doi:10.1186/s12575-025-00302-4 https://pubmed.ncbi.nlm.nih.gov/41214544/
[10] Shi Y, Ma P. Pharmacological effects of Astragalus polysaccharides in treating neurodegenerative diseases. Front Pharmacol. 15:1449101. Published 2024 None. doi:10.3389/fphar.2024.1449101 https://pubmed.ncbi.nlm.nih.gov/39156112/
[11] Song K, Yu JY, Li J, Li M, Peng LY, Yi PF. Astragaloside IV Regulates cGAS-STING Signaling Pathway to Alleviate Immunosuppression Caused by PRRSV Infection. Viruses. 2023;15(7). Published 2023 Jul 20. doi:10.3390/v15071586 https://pubmed.ncbi.nlm.nih.gov/37515271/
[12] Liu S, Zhang Y, Lv J, Zhou L. Traditional Chinese Medicine for Allergic Rhinitis: Mechanisms, Evidence, and Gut-Immune Axis Targets. J Asthma Allergy. 19:1-23. Published 2026 None. doi:10.2147/JAA.S571460 https://pubmed.ncbi.nlm.nih.gov/41541602/
[13] Chen N, Li L, Han Y, Chen Z. The Role of Gut Microbiota in the Modulation of Pulmonary Immune Response to Viral Infection Through the Gut-Lung Axis. J Inflamm Res. 18:11755-11781. Published 2025 None. doi:10.2147/JIR.S525880 https://pubmed.ncbi.nlm.nih.gov/40901024/
[14] Fan N, Zhang Y, Ge Z, et al. A safe saponin-based nano-strategy for manganese-mediated STING activation. J Control Release. 2025;388(Pt 1):114303. doi:10.1016/j.jconrel.2025.114303 https://pubmed.ncbi.nlm.nih.gov/41077145/
[15] Kong C, Sun J, Hu X, Li G, Wu S. A tumor targeted nano micelle carrying astragaloside IV for combination treatment of bladder cancer. Sci Rep. 2024;14(1):17704. Published 2024 Jul 31. doi:10.1038/s41598-024-66010-3 https://pubmed.ncbi.nlm.nih.gov/39085255/
[16] D’Avino D, Cerqua I, Ullah H, et al. Beneficial Effects of Astragalus membranaceus (Fisch.) Bunge Extract in Controlling Inflammatory Response and Preventing Asthma Features. Int J Mol Sci. 2023;24(13). Published 2023 Jun 30. doi:10.3390/ijms241310954 https://pubmed.ncbi.nlm.nih.gov/37446131/
[17] Gong G, Yu H, Zheng Y, et al. Astragaloside IV, a saponin from Astragalus membranaceus var. mongholicus, induces expressions of heme recycle proteins via signaling of Nrf2/ARE in cultured macrophages. J Ethnopharmacol. 265:113389. doi:10.1016/j.jep.2020.113389 https://pubmed.ncbi.nlm.nih.gov/32920134/
[18] Lim SM, Park HB, Jin JO. Polysaccharide from Astragalus membranaceus promotes the activation of human peripheral blood and mouse spleen dendritic cells. Chin J Nat Med. 2021;19(1):56-62. doi:10.1016/S1875-5364(21)60006-7 https://pubmed.ncbi.nlm.nih.gov/33516452/
[19] Sheik A, Kim K, Varaprasad GL, et al. The anti-cancerous activity of adaptogenic herb Astragalus membranaceus. Phytomedicine. 91:153698. doi:10.1016/j.phymed.2021.153698 https://pubmed.ncbi.nlm.nih.gov/34479785/
[20] Zhang X, Qu X, Zou Y. The Effect of Astragalus on Humoral and Cellular Immune Response: A Systematic Review and Meta-Analysis of Human Studies. Complement Med Res. 2023;30(6):535-543. doi:10.1159/000534826 https://pubmed.ncbi.nlm.nih.gov/37952511/
[21] Ding C, Wang Q, Yuan S, et al. Astragalus polysaccharides enhance the immune response and resistance of grass carp against grass carp reovirus. Int J Biol Macromol. 352:151046. Published online Feb 21,2026. doi:10.1016/j.ijbiomac.2026.151046 https://pubmed.ncbi.nlm.nih.gov/41730448/
[22] Tang Z, Cheng L, Li M, Huang C. Astragaloside IV Alleviates Systemic Lupus Erythematosus by Modulating ITGB1/PTK2/p38 Pathway: Integrated Network Pharmacology and Experimental Validation. Drug Des Devel Ther. 19:8967-8984. Published 2025 None. doi:10.2147/DDDT.S554510 https://pubmed.ncbi.nlm.nih.gov/41058946/
[23] Xu Z, Xu H, Zhang L, et al. Astragalus polysaccharide (APS) improves the immune function in diet-induced obese (DIO) mice. Pak J Pharm Sci. 2024;37(3):613-620. https://pubmed.ncbi.nlm.nih.gov/39340852/
[24] Liu X, Wang S, Wu X, et al. Astragaloside IV Alleviates Depression in Rats by Modulating Intestinal Microbiota, T-Immune Balance, and Metabolome. J Agric Food Chem. 2024;72(1):259-273. doi:10.1021/acs.jafc.3c04063 https://pubmed.ncbi.nlm.nih.gov/38064688/
[25] Chen Y, Wei X, Rui B, et al. Probiotic Fermentation of Astragalus membranaceus and Raphani Semen Ameliorates Cyclophosphamide-Induced Immunosuppression Through Intestinal Short-Chain Fatty Acid-Dependent or -Independent Regulation of B Cell Function. Biology (Basel). 2025;14(3). Published 2025 Mar 19. doi:10.3390/biology14030312 https://pubmed.ncbi.nlm.nih.gov/40136568/
[26] Chen XY, Han HF, He ZY, Xu XG. Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study. Evid Based Complement Alternat Med. 2021:2252832. Published 2021 None. doi:10.1155/2021/2252832 https://pubmed.ncbi.nlm.nih.gov/34567206/
[27] Yao J, Liu J, He Y, et al. Systems pharmacology reveals the mechanism of Astragaloside IV in improving immune activity on cyclophosphamide-induced immunosuppressed mice. J Ethnopharmacol. 313:116533. doi:10.1016/j.jep.2023.116533 https://pubmed.ncbi.nlm.nih.gov/37100262/
[28] Zhu Y, Su Y, Zhang J, et al. Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR‑mediated autophagy. Mol Med Rep. 2021;23(6). doi:10.3892/mmr.2021.12076 https://pubmed.ncbi.nlm.nih.gov/33846768/
[29] Zhong Y, Liu W, Xiong Y, et al. Astragaloside Ⅳ alleviates ulcerative colitis by regulating the balance of Th17/Treg cells. Phytomedicine. 104:154287. doi:10.1016/j.phymed.2022.154287 https://pubmed.ncbi.nlm.nih.gov/35752072/
[30] Chen JL, Liu XJ, Zhao HY, Zhao GH, Gao MD. Network pharmacology identifies AKR1C3 and KYNU as potential targets of Astragalus Membranaceus and Ephedra in pediatric obesity-associated asthma. Sci Rep. 2025;16(1):1817. Published 2025 Dec 9. doi:10.1038/s41598-025-31533-w https://pubmed.ncbi.nlm.nih.gov/41366037/
[31] Chen Q, Chen P, Bi C, et al. Screening immunomodulatory Q-markers in Astragali Radix based on UHPLC-QTOF-MS analysis and spectrum-effect relationship. Biomed Chromatogr. 2024;38(12):e6015. doi:10.1002/bmc.6015 https://pubmed.ncbi.nlm.nih.gov/39385660/
[32] Zhang J, Huang J, Lan J, et al. Astragaloside IV protects against autoimmune myasthenia gravis in rats via regulation of mitophagy and apoptosis. Mol Med Rep. 2024;30(1). doi:10.3892/mmr.2024.13253 https://pubmed.ncbi.nlm.nih.gov/38785143/
[33] Xu H, Yang J, Zhang Y, et al. Targeting mitochondrial permeability and cytosolic mtDNA release: Astragaloside IV suppresses cGAS-STING signaling pathway to protect against cadmium-induced hepatotoxicity. Free Radic Biol Med. 246:239-251. doi:10.1016/j.freeradbiomed.2026.01.027 https://pubmed.ncbi.nlm.nih.gov/41565084/
[34] Ye D, Zhao Q, Ding D, Ma BL. Preclinical pharmacokinetics-related pharmacological effects of orally administered polysaccharides from traditional Chinese medicines: A review. Int J Biol Macromol. 252:126484. doi:10.1016/j.ijbiomac.2023.126484 https://pubmed.ncbi.nlm.nih.gov/37625759/
[35] Qu T, Suo S, Yan L, Wang L, Liang T. Anti-Inflammatory Effects of Astragaloside IV-Chitosan Nanoparticles and Associated Anti-Inflammatory Mechanisms Based on Liquid Chromatography-Mass Spectrometry Metabolomic Analysis of RAW264.7 Cells. Chem Biodivers. 2025;22(6):e202402234. doi:10.1002/cbdv.202402234 https://pubmed.ncbi.nlm.nih.gov/39891602/
[36] Wu S, Zhou M, Zhou H, Han L, Liu H. Astragaloside IV- loaded biomimetic nanoparticles target IκBα to regulate neutrophil extracellular trap formation for sepsis therapy. J Nanobiotechnology. 2025;23(1):155. Published 2025 Feb 28. doi:10.1186/s12951-025-03260-x https://pubmed.ncbi.nlm.nih.gov/40022068/
[37] Chen Y, Hu Z, Jiang J, et al. Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats. Front Pharmacol. 14:1282062. Published 2023 None. doi:10.3389/fphar.2023.1282062 https://pubmed.ncbi.nlm.nih.gov/38094890/
[38] Jia H, Qi Y, Wang H, Zhang F, Wu J, Zhang Z. Preclinical research and potential clinical application of traditional Chinese medicine in cancer treatment: take Astragalus and Dioscorea opposita as an example. Front Pharmacol. 16:1662341. Published 2025 None. doi:10.3389/fphar.2025.1662341 https://pubmed.ncbi.nlm.nih.gov/41079717/
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