Astragalus Membranaceus for Type 2 Diabetes Mellitus and Its Complications: From Molecular Mechanisms to Therapeutic Potential
DOI:
https://doi.org/10.71204/83zf0y22Keywords:
Astragalus Membranaceus, Astragalus Polysaccharides, Astragaloside Ⅳ, Flavonoids, Type 2 diabetes mellitus, Diabetic ComplicationsAbstract
Astragalus membranaceus is a traditional Chinese medicine widely used in the management of diabetes mellitus. Its major bioactive constituents—astragalus polysaccharides (APS), astragaloside IV (AS-IV), and flavonoids—demonstrate significant anti-diabetic properties. This review summarizes current evidence on the therapeutic potential and molecular mechanisms of A. membranaceus and its major components in treating T2DM and its complications. Literature was retrieved from six databases: PubMed, Science Direct, Academic Journals, Web of Science, Research Gate, and Google Scholar. Search terms included “type 2 diabetes mellitus”, “Astragalus membranaceus”, “polysaccharides”, “saponins”, “flavonoids”, and their combinations. Bioactive compounds from A. membranaceus modulate glucose metabolism and ameliorate insulin resistance (IR). APS restores glucose homeostasis via the PI3K/Akt and AMPK pathways, alleviates endoplasmic reticulum (ER) stress, and regulates gut microbiota. It also confers protection against diabetic cardiomyopathy, nephropathy, cognitive dysfunction, bladder dysfunction, and ulcers through anti-inflammatory, antioxidative, and pro-autophagic activities. AS-IV improves dysregulated glucolipid metabolism by modulating the AMPK/mTOR, ERK1/2, and NF-κB pathways. Flavonoids exert renoprotective effects by mitigating mitochondrial dysfunction and inflammation. A. membranaceus and its bioactive constituents provide a multitargeted strategy to alleviate T2DM and its complications by regulating metabolic, inflammatory, and oxidative stress pathways. However, poor oral bioavailability remains a major limitation for clinical translation. Recent advances in structural modifications and novel delivery systems offer promising avenues to overcome this challenge. As an alternative or adjunctive therapy, A. membranaceus holds considerable potential in diabetes management.
References
Agus, A., Clement, K., Sokol, H. (2021). Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut, 70(6), 1174-1182. DOI: https://doi.org/10.1136/gutjnl-2020-323071
Agyemang, K., Han, L., Liu, E., Zhang, Y., Wang, T., Gao, X. (2013). Recent advances in Astragalus membranaceus anti-diabetic research: Pharmacological effects of its phytochemical constituents. Evid Based Complement Alternat Med, 2013, 654643. DOI: https://doi.org/10.1155/2013/654643
American Diabetes Association Professional Practice, C. (2024). 2. Diagnosis and classification of diabetes: Standards of care in diabetes-2024. Diabetes Care, 47(Suppl 1), S20-S42. DOI: https://doi.org/10.2337/dc24-S002
Bakke, J., Haj, F. G. (2015). Protein-tyrosine phosphatase 1B substrates and metabolic regulation. Semin Cell Dev Biol, 37, 58-65. DOI: https://doi.org/10.1016/j.semcdb.2014.09.020
Bhatia, D., Capili, A., Choi, M. E. (2020). Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches. Kidney Res Clin Pract, 39(3), 244-258. DOI: https://doi.org/10.23876/j.krcp.20.082
Borse, S. P., Chhipa, A. S., Sharma, V., Singh, D. P., Nivsarkar, M. (2021). Management of type 2 diabetes: Current strategies, unfocussed aspects, challenges, and alternatives. Med Princ Pract, 30(2), 109-121. DOI: https://doi.org/10.1159/000511002
Cao, Y., Deng, B., Zhang, S., Gao, H., Song, P., Zhang, J., Zhao, J. (2021). Astragalus polysaccharide regulates brown adipogenic differentiation through miR-1258-5p-modulated cut-like homeobox 1 expression. Acta Biochim Biophys Sin (Shanghai), 53(12), 1713-1722. DOI: https://doi.org/10.1093/abbs/gmab151
Capece, D., Verzella, D., Flati, I., Arboretto, P., Cornice, J., Franzoso, G. (2022). NF-kappaB: blending metabolism, immunity, and inflammation. Trends Immunol, 43(9), 757-775. DOI: https://doi.org/10.1016/j.it.2022.07.004
Carling, D. (2017). AMPK signalling in health and disease. Curr Opin Cell Biol, 45, 31-37. DOI: https://doi.org/10.1016/j.ceb.2017.01.005
Chen, G., Jiang, N., Zheng, J., Hu, H., Yang, H., Lin, A., Hu, B., Liu, H. (2023a). Structural characterization and anti-inflammatory activity of polysaccharides from Astragalus membranaceus. Int J Biol Macromol, 241, 124386. DOI: https://doi.org/10.1016/j.ijbiomac.2023.124386
Chen, G., Yang, R., Yang, X., Jiang, J., Guo, Y., Xu, M., Chen, Y., Hou, Y., Zhang, C., Wang, N., Feng, Y. (2025). Mulberry twig alkaloids for type 2 diabetes mellitus: a systematic review and meta-analysis. Front Pharmacol, 16, 1475080. DOI: https://doi.org/10.3389/fphar.2025.1475080
Chen, J., Peng, H., Chen, C., Wang, Y., Sang, T., Cai, Z., Zhao, Q., Chen, S., Lin, X., Eling, T., Wang, X. (2022). NAG-1/GDF15 inhibits diabetic nephropathy via inhibiting AGE/RAGE-mediated inflammation signaling pathways in C57BL/6 mice and HK-2 cells. Life Sci, 311(Pt A), 121142. DOI: https://doi.org/10.1016/j.lfs.2022.121142
Chen, W., Xia, Y., Zhao, X., Wang, H., Chen, W., Yu, M., Li, Y., Ye, H., Zhang, Y. (2012a). The critical role of Astragalus polysaccharides for the improvement of PPARalpha [ correction of PPRAalpha]-mediated lipotoxicity in diabetic cardiomyopathy. PLoS One, 7(10), e45541. DOI: https://doi.org/10.1371/journal.pone.0045541
Chen, X., Wang, H., Jiang, M., Zhao, J., Fan, C., Wang, Y., Peng, W. (2018). Huangqi (astragalus) decoction ameliorates diabetic nephropathy via IRS1-PI3K-GLUT signaling pathway. Am J Transl Res, 10(8), 2491-2501.
Chen, X. Y., Wang, T. T., Shen, Q., Ma, H., Li, Z. H., Yu, X. N., Huang, X. F., Qing, L. S., Luo, P. (2024). Preclinical investigations on anti-fibrotic potential of long-term oral therapy of sodium astragalosidate in animal models of cardiac and renal fibrosis. ACS Pharmacol Transl Sci, 7(2), 421-431. DOI: https://doi.org/10.1021/acsptsci.3c00264
Chen, Y., Rui, R., Wang, L., Wang, H., Zhu, B., Cao, A. (2023b). Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway. BMC Complement Med Ther, 23(1), 209. DOI: https://doi.org/10.1186/s12906-023-04029-1
Chen, Y. F., Wang, C. Y., Li, W. M., Gao, Y., Wu, Q. H., Tang, C. P., Wang, H., Yang, C. Y. (2012b). [Effect of Huangqi gegen decoction (HGD) on TGF-beta1/Smad3 pathway in diabetic cardiomyopathy rats]. Zhong Yao Cai, 35(11), 1809-1813.
Chen, Z., Liang, H., Yan, X., Liang, Q., Bai, Z., Xie, T., Dai, J., Zhao, X., Xiao, Y. (2023c). Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268/PRLR pathway. Ren Fail, 45(2), 2284211. DOI: https://doi.org/10.1080/0886022X.2023.2284211
Cheng, X. D., Wei, M. G. (2014). Profiling the metabolism of astragaloside IV by ultra performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry. Molecules, 19(11), 18881-18896. DOI: https://doi.org/10.3390/molecules191118881
Chi, L., Niu, H., Niu, Y., Yao, R., Shi, D., Lu, B., Pang, Z. (2025). Trigonella foenum-graecum L. ameliorates metabolism-associated fatty liver disease in type 2 diabetic mice: a multi-omics mechanism analysis. J Ethnopharmacol, 348, 119862. DOI: https://doi.org/10.1016/j.jep.2025.119862
Commission, N. P. (2020). Pharmacopoeia of the peoples republic of China. Chemical Industry Press, Beijing.
Coutinho-Wolino, K. S., Almeida, P. P., Mafra, D., Stockler-Pinto, M. B. (2022). Bioactive compounds modulating Toll-like 4 receptor (TLR4)-mediated inflammation: pathways involved and future perspectives. Nutr Res, 107, 96-116. DOI: https://doi.org/10.1016/j.nutres.2022.09.001
Cui, F. Q., Gao, Y. B., Wang, Y. F., Meng, Y., Cai, Z., Shen, C., Jiang, X. C., Zhao, W. J. (2021). Effect of Tang-Shen-Ning decoction on podocyte epithelial-esenchymal transformation via inhibiting Wnt/beta-catenin pathway in diabetic mice. Ann Palliat Med, 10(12), 12921-12936. DOI: https://doi.org/10.21037/apm-20-602
Darenskaya, M., Kolesnikov, S., Semenova, N., Kolesnikova, L. (2023). Diabetic nephropathy: Significance of determining oxidative stress and opportunities for antioxidant therapies. Int J Mol Sci, 24(15), 12378. DOI: https://doi.org/10.3390/ijms241512378
Dillmann, W. H. (2019). Diabetic cardiomyopathy. Circ Res, 124(8), 1160-1162. DOI: https://doi.org/10.1161/CIRCRESAHA.118.314665
Du, R., Xu, F., Wei, D., Wei, Y., Wang, Z., Wang, Z. (2024). Pharmacokinetics of two triterpenoid saponins and three flavonoids in Astragalus membranaceus leaves by UHPLC-MS/MS. J Pharm Biomed Anal, 251, 116419. DOI: https://doi.org/10.1016/j.jpba.2024.116419
Du, X., Liu, M., Tai, W., Yu, H., Hao, X., Loor, J. J., Jiang, Q., Fang, Z., Gao, X., Fan, M., Gao, W., Lei, L., Song, Y., Wang, Z., Zhang, C., Liu, G., Li, X. (2022a). Tumor necrosis factor-alpha promotes lipolysis and reduces insulin sensitivity by activating nuclear factor kappa B and c-Jun N-terminal kinase in primary bovine adipocytes. J Dairy Sci, 105(10), 8426-8438. DOI: https://doi.org/10.3168/jds.2022-22009
Du, Y., Wan, H., Huang, P., Yang, J., He, Y. (2022b). A critical review of Astragalus polysaccharides: From therapeutic mechanisms to pharmaceutics. Biomed Pharmacother, 147, 112654. DOI: https://doi.org/10.1016/j.biopha.2022.112654
Dun, C., Liu, J., Qiu, F., Wu, X., Wang, Y., Zhao, Y., Gu, P. (2016). Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model. Neuropsychiatr Dis Treat, 12, 1617-1621. DOI: https://doi.org/10.2147/NDT.S106123
Efiong, E. E., Maedler, K., Effa, E., Osuagwu, U. L., Peters, E., Ikebiuro, J. O., Soremekun, C., Ihediwa, U., Niu, J., Fuchs, M., Bazireh, H., Bassey, A. L., Amadi, P. U., Dong, Q., Kimani, N. M., Chukwuanukwu, R. C., Tuenter, E., Sharma, S., Grallert, H. (2025). Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights. Diabetol Metab Syndr, 17(1), 192. DOI: https://doi.org/10.1186/s13098-025-01726-4
Elabd, H., Wang, H. P., Shaheen, A., Matter, A. (2020). Astragalus membranaceus nanoparticles markedly improve immune and anti-oxidative responses; and protection against Aeromonas veronii in Nile tilapia Oreochromis niloticus. Fish Shellfish Immunol, 97, 248-256. DOI: https://doi.org/10.1016/j.fsi.2019.12.025
Elmasry, K., Ibrahim, A. S., Saleh, H., Elsherbiny, N., Elshafey, S., Hussein, K. A., Al-Shabrawey, M. (2018). Role of endoplasmic reticulum stress in 12/15-lipoxygenase-induced retinal microvascular dysfunction in a mouse model of diabetic retinopathy. Diabetologia, 61(5), 1220-1232. DOI: https://doi.org/10.1007/s00125-018-4560-z
Engin, A. B. (2017). What is lipotoxicity? Adv Exp Med Biol, 960, 197-220. DOI: https://doi.org/10.1007/978-3-319-48382-5_8
Entezari, M., Hashemi, D., Taheriazam, A., Zabolian, A., Mohammadi, S., Fakhri, F., Hashemi, M., Hushmandi, K., Ashrafizadeh, M., Zarrabi, A., Ertas, Y. N., Mirzaei, S., Samarghandian, S. (2022). AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation. Biomed Pharmacother, 146, 112563. DOI: https://doi.org/10.1016/j.biopha.2021.112563
Esquejo, R. M., Albuquerque, B., Sher, A., Blatnik, M., Wald, K., Peloquin, M., Delmore, J., Kindt, E., Li, W., Young, J. D., Cameron, K., Miller, R. A. (2022). AMPK activation is sufficient to increase skeletal muscle glucose uptake and glycogen synthesis but is not required for contraction-mediated increases in glucose metabolism. Heliyon, 8(10), e11091. DOI: https://doi.org/10.1016/j.heliyon.2022.e11091
Fan, Y., Fan, H., Li, P., Liu, Q., Huang, L., Zhou, Y. (2022). Mitogen-activating protein kinase kinase kinase kinase-3, inhibited by Astragaloside IV through H3 lysine 4 monomethylation, promotes the progression of diabetic nephropathy by inducing apoptosis. Bioengineered, 13(5), 11517-11529. DOI: https://doi.org/10.1080/21655979.2022.2068822
Fang, C., Pan, J., Qu, N., Lei, Y., Han, J., Zhang, J., Han, D. (2022). The AMPK pathway in fatty liver disease. Front Physiol, 13, 970292. DOI: https://doi.org/10.3389/fphys.2022.970292
Farmaki, P., Damaskos, C., Garmpis, N., Garmpi, A., Savvanis, S., Diamantis, E. (2020). Complications of the type 2 diabetes mellitus. Curr Cardiol Rev, 16(4), 249-251. DOI: https://doi.org/10.2174/1573403X1604201229115531
Flessa, C. M., Kyrou, I., Nasiri-Ansari, N., Kaltsas, G., Kassi, E., Randeva, H. S. (2022). Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD). J Cell Biochem, 123(10), 1585-1606. DOI: https://doi.org/10.1002/jcb.30247
Gao, D., Bing, C., Griffiths, H. R. (2025). Disrupted adipokine secretion and inflammatory responses in human adipocyte hypertrophy. Adipocyte, 14(1), 2485927. DOI: https://doi.org/10.1080/21623945.2025.2485927
Gong, L., Zou, Z., Huang, L., Guo, S., Xing, D. (2020). Photobiomodulation therapy decreases free fatty acid generation and release in adipocytes to ameliorate insulin resistance in type 2 diabetes. Cell Signal, 67, 109491. DOI: https://doi.org/10.1016/j.cellsig.2019.109491
Gong, P., Xiao, X., Wang, S., Shi, F., Liu, N., Chen, X., Yang, W., Wang, L., Chen, F. (2021). Hypoglycemic effect of astragaloside IV via modulating gut microbiota and regulating AMPK/SIRT1 and PI3K/AKT pathway. J Ethnopharmacol, 281, 114558. DOI: https://doi.org/10.1016/j.jep.2021.114558
Gu, Y., Wang, G., Pan, G., Fawcett, J. P., A, J., Sun, J. (2004). Transport and bioavailability studies of astragaloside IV, an active ingredient in Radix Astragali. Basic Clin Pharmacol Toxicol, 95(6), 295-298. DOI: https://doi.org/10.1111/j.1742-7843.2004.t01-1-pto950508.x
Gui, D., Huang, J., Guo, Y., Chen, J., Chen, Y., Xiao, W., Liu, X., Wang, N. (2013). Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-kappaB-mediated inflammatory genes expression. Cytokine, 61(3), 970-977. DOI: https://doi.org/10.1016/j.cyto.2013.01.008
Guo, M., Gao, J., Jiang, L., Dai, Y. (2023). Astragalus polysaccharide ameliorates renal inflammatory responses in a diabetic nephropathy by suppressing the TLR4/NF-kappaB pathway. Drug Des Devel Ther, 17, 2107-2118. DOI: https://doi.org/10.2147/DDDT.S411211
Han, H., Cao, A., Wang, L., Guo, H., Zang, Y., Li, Z., Zhang, X., Peng, W. (2017). Huangqi decoction ameliorates streptozotocin-induced rat diabetic nephropathy through antioxidant and regulation of the TGF-beta/MAPK/PPAR-gamma signaling. Cell Physiol Biochem, 42(5), 1934-1944. DOI: https://doi.org/10.1159/000479834
He, K. Q., Li, W. Z., Chai, X. Q., Yin, Y. Y., Jiang, Y., Li, W. P. (2018). Astragaloside IV prevents kidney injury caused by iatrogenic hyperinsulinemia in a streptozotocin‑induced diabetic rat model. Int J Mol Med, 41(2), 1078-1088. DOI: https://doi.org/10.3892/ijmm.2017.3265
Herzig, S., Shaw, R. J. (2018). AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 19(2), 121-135. DOI: https://doi.org/10.1038/nrm.2017.95
Hetz, C., Zhang, K., Kaufman, R. J. (2020). Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol, 21(8), 421-438. DOI: https://doi.org/10.1038/s41580-020-0250-z
Hou, M., Leng, Y., Shi, Y., Tan, Z., Min, X. (2023). Astragalus membranaceus as a drug candidate for inflammatory bowel disease: The preclinical evidence. Am J Chin Med, 51(6), 1501-1526. DOI: https://doi.org/10.1142/S0192415X23500684
Hu, H., Tian, M., Ding, C., Yu, S. (2018). The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol, 9, 3083. DOI: https://doi.org/10.3389/fimmu.2018.03083
Huang, C. R., Wang, G. J., Wu, X. L., Li, H., Xie, H. T., Lv, H., Sun, J. G. (2006). Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells. Eur J Drug Metab Pharmacokinet, 31(1), 5-10. DOI: https://doi.org/10.1007/BF03190635
Huang, D., Shen, P., Wang, C., Gao, J., Ye, C., Wu, F. (2022a). Calycosin plays a protective role in diabetic kidney disease through the regulation of ferroptosis. Pharm Biol, 60(1), 990-996. DOI: https://doi.org/10.1080/13880209.2022.2067572
Huang, Q., Chen, H., Yin, K., Shen, Y., Lin, K., Guo, X., Zhang, X., Wang, N., Xin, W., Xu, Y., Gui, D. (2022b). Formononetin attenuates renal tubular injury and mitochondrial damage in diabetic nephropathy partly via regulating Sirt1/PGC-1alpha pathway. Front Pharmacol, 13, 901234. DOI: https://doi.org/10.3389/fphar.2022.901234
Huang, R., Hui, Z., Wei, S., Li, D., Li, W., Daping, W., Alahdal, M. (2022c). IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis. J Cell Physiol, 237(1), 118-127. DOI: https://doi.org/10.1002/jcp.30537
Huang, T. S., Wu, T., Wu, Y. D., Li, X. H., Tan, J., Shen, C. H., Xiong, S. J., Feng, Z. Q., Gao, S. F., Li, H., Cai, W. B. (2023). Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice. Nat Commun, 14(1), 390. DOI: https://doi.org/10.1038/s41467-023-35944-z
Huang, X., Liu, G., Guo, J., Su, Z. (2018). The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci, 14(11), 1483-1496. DOI: https://doi.org/10.7150/ijbs.27173
Hwang, J., Zhang, W., Dhananjay, Y., An, E. K., Kwak, M., You, S., Lee, P. C., Jin, J. O. (2021). Astragalus membranaceus polysaccharides potentiate the growth-inhibitory activity of immune checkpoint inhibitors against pulmonary metastatic melanoma in mice. Int J Biol Macromol, 182, 1292-1300. DOI: https://doi.org/10.1016/j.ijbiomac.2021.05.073
Iurlaro, R., Munoz-Pinedo, C. (2016). Cell death induced by endoplasmic reticulum stress. FEBS J, 283(14), 2640-2652. DOI: https://doi.org/10.1111/febs.13598
Jeon, J. Y., Kim, D. J. (2022). Cardiovascular disease in patients with type 2 diabetes. J Diabetes Investig, 13(4), 614-616. DOI: https://doi.org/10.1111/jdi.13742
Jiang, B., Yang, Y., Jin, H., Shang, W., Zhou, L., Qian, L., Chen, M. (2008). Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes. Phytother Res, 22(11), 1434-1439. DOI: https://doi.org/10.1002/ptr.2434
Jiang, Q., Li, C., Jiang, Y., Ye, Z., Xu, G., Zhang, Y., Yang, F., Xiao, J., Li, C. (2025). BMP10 in cardiovascular disease: From pathogenesis to therapeutic strategies. Front Biosci (Landmark Ed), 30(7), 31356. DOI: https://doi.org/10.31083/FBL31356
Jiangbo, Z., Xuying, W., Yuping, Z., Xili, M., Yiwen, Z., Tianbao, Z. (2009). Effect of astragaloside IV on the embryo-fetal development of Sprague-Dawley rats and New Zealand White rabbits. J Appl Toxicol, 29(5), 381-385. DOI: https://doi.org/10.1002/jat.1422
Jin, Q., Liu, T., Qiao, Y., Liu, D., Yang, L., Mao, H., Ma, F., Wang, Y., Peng, L., Zhan, Y. (2023). Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols. Front Immunol, 14, 1185317. DOI: https://doi.org/10.3389/fimmu.2023.1185317
Jing, P., Hongzheng, H., Zhenqi, W. U., Meijuan, Z., Zuojing, L. I., Gang, C. (2024). Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials. J Tradit Chin Med, 44(2), 229-242.
Ke, P. Y. (2019). Diverse functions of autophagy in liver physiology and liver diseases. Int J Mol Sci, 20(2), 300. DOI: https://doi.org/10.3390/ijms20020300
Khalid, M., Petroianu, G., Adem, A. (2022). Advanced glycation end products and diabetes mellitus: Mechanisms and perspectives. Biomolecules, 12(4), 542. DOI: https://doi.org/10.3390/biom12040542
Knapp, M., Tu, X., Wu, R. (2019). Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy. Acta Pharmacol Sin, 40(1), 1-8. DOI: https://doi.org/10.1038/s41401-018-0042-6
Leaf, I. A., Duffield, J. S. (2017). What can target kidney fibrosis? Nephrol Dial Transplant, 32(suppl_1), i89-i97. DOI: https://doi.org/10.1093/ndt/gfw388
Lei, L., Huan, Y., Liu, Q., Li, C., Cao, H., Ji, W., Gao, X., Fu, Y., Li, P., Zhang, R., Abliz, Z., Liu, Y., Liu, S., Shen, Z. (2022). Morus alba L. (Sangzhi) Alkaloids promote insulin secretion, restore diabetic beta-cell function by preventing dedifferentiation and apoptosis. Front Pharmacol, 13, 841981. DOI: https://doi.org/10.3389/fphar.2022.841981
Lei, Y., Yu, H., Ding, S., Liu, H., Liu, C., Fu, R. (2024). Molecular mechanism of ATF6 in unfolded protein response and its role in disease. Heliyon, 10(5), e25937. DOI: https://doi.org/10.1016/j.heliyon.2024.e25937
Leng, B., Tang, F., Lu, M., Zhang, Z., Wang, H., Zhang, Y. (2018). Astragaloside IV improves vascular endothelial dysfunction by inhibiting the TLR4/NF-kappaB signaling pathway. Life Sci, 209, 111-121. DOI: https://doi.org/10.1016/j.lfs.2018.07.053
Leonidas, D. D., Zographos, S. E., Tsitsanou, K. E., Skamnaki, V. T., Stravodimos, G., Kyriakis, E. (2021). Glycogen phosphorylase revisited: extending the resolution of the R- and T-state structures of the free enzyme and in complex with allosteric activators. Acta Crystallogr F Struct Biol Commun, 77(Pt 9), 303-311. DOI: https://doi.org/10.1107/S2053230X21008542
Li, G., Liu, C., Yang, L., Feng, L., Zhang, S., An, J., Li, J., Gao, Y., Pan, Z., Xu, Y., Liu, J., Wang, Y., Yan, J., Cui, J., Qi, Z., Yang, L. (2023). Syringaresinol protects against diabetic nephropathy by inhibiting pyroptosis via NRF2-mediated antioxidant pathway. Cell Biol Toxicol, 39(3), 621-639. DOI: https://doi.org/10.1007/s10565-023-09790-0
Li, J., Wang, D., Li, F., Liao, X., Yin, D., Wei, T., Le, Y., Cui, X., Yang, J., Wei, R., Hong, T. (2025a). Mulberry twig (Sangzhi) alkaloids induce pancreatic alpha-to-beta-cell phenotypic conversion in type 2 diabetic mice. Phytomedicine, 141, 156685. DOI: https://doi.org/10.1016/j.phymed.2025.156685
Li, M. Y., Ding, J. Q., Tang, Q., Hao, M. M., Wang, B. H., Wu, J., Yu, L. Z., Jiao, M., Luo, B. H., Xie, M., Zhu, H. L. (2019a). SIRT1 activation by SRT1720 attenuates bone cancer pain via preventing Drp1-mediated mitochondrial fission. Biochim Biophys Acta Mol Basis Dis, 1865(3), 587-598. DOI: https://doi.org/10.1016/j.bbadis.2018.12.017
Li, S., Hu, X., Liu, F., Hu, W. (2025b). Bioactive components and clinical potential of Astragalus species. Front Pharmacol, 16, 1585697. DOI: https://doi.org/10.3389/fphar.2025.1585697
Li, S., Sun, Y., Huang, J., Wang, B., Gong, Y., Fang, Y., Liu, Y., Wang, S., Guo, Y., Wang, H., Xu, Z., Guo, Y. (2020). Anti-tumor effects and mechanisms of Astragalus membranaceus (AM) and its specific immunopotentiation: Status and prospect. J Ethnopharmacol, 258, 112797. DOI: https://doi.org/10.1016/j.jep.2020.112797
Li, X., Zhao, T., Gu, J., Wang, Z., Lin, J., Wang, R., Duan, T., Li, Z., Dong, R., Wang, W., Hong, K. F., Liu, Z., Huang, W., Gui, D., Zhou, H., Xu, Y. (2022a). Intake of flavonoids from Astragalus membranaceus ameliorated brain impairment in diabetic mice via modulating brain-gut axis. Chin Med, 17(1), 22. DOI: https://doi.org/10.1186/s13020-022-00578-8
Li, Y., Li, H. Y., Shao, J., Zhu, L., Xie, T. H., Cai, J., Wang, W., Cai, M. X., Wang, Z. L., Yao, Y., Wei, T. T. (2022b). GRP75 modulates endoplasmic reticulum-mitochondria coupling and accelerates Ca(2+)-dependent endothelial cell apoptosis in diabetic retinopathy. Biomolecules, 12(12), 1778. DOI: https://doi.org/10.3390/biom12121778
Li, Z., Deng, W., Cao, A., Zang, Y., Wang, Y., Wang, H., Wang, L., Peng, W. (2019b). Huangqi decoction inhibits hyperglycemia-induced podocyte apoptosis by down-regulated Nox4/p53/Bax signaling in vitro and in vivo. Am J Transl Res, 11(5), 3195-3212.
Li, Z., Yang, W., Yang, Y., Wu, J., Luo, P., Liu, Y. (2022c). The astragaloside IV derivative LS-102 ameliorates obesity-related nephropathy. Drug Des Devel Ther, 16, 647-664. DOI: https://doi.org/10.2147/DDDT.S346546
Liang, J., He, J., Gao, Y., Zhu, Z. (2021). Exploring the potential mechanism of Tang-Shen-Ning Decoction against diabetic nephropathy based on the combination of network pharmacology and experimental validation. Evid Based Complement Alternat Med, 2021, 1025053. DOI: https://doi.org/10.1155/2021/1025053
Liang, S., Xu, S., Ye, S., Liang, L., Li, H., Liu, J., Zhang, Y., Zou, F., Liang, X., Tan, B., Cao, H. (2025). Astragalus polysaccharides ameliorate diabetic bladder dysfunction via normalization of neuromuscular conduction. J Agric Food Chem, 73(10), 5970-5980. DOI: https://doi.org/10.1021/acs.jafc.4c11577
Lin, Y. Q., Yu, F., Chen, H. J., Deng, Y. R., Lin, J., Xu, Y., Zheng, X., Zhang, J. W., Liu, J. F. (2024). Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis. Ren Fail, 46(2), 2359033. DOI: https://doi.org/10.1080/0886022X.2024.2359033
Liu, P., Peng, Q. H., Tong, P., Li, W. J. (2019). Astragalus polysaccharides suppresses high glucose-induced metabolic memory in retinal pigment epithelial cells through inhibiting mitochondrial dysfunction-induced apoptosis by regulating miR-195. Mol Med, 25(1), 21. DOI: https://doi.org/10.1186/s10020-019-0088-z
Liu, P. Y., Hong, K. F., Liu, Y. D., Sun, Z. Y., Zhao, T. T., Li, X. L., Lao, C. C., Tan, S. F., Zhang, H. Y., Zhao, Y. H., Xie, Y., Xu, Y. H. (2024a). Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease. Chin Med, 19(1), 27. DOI: https://doi.org/10.1186/s13020-024-00903-3
Liu, S., Wang, L., Zhang, Z., Leng, Y., Yang, Y., Fu, X., Xie, H., Gao, H., Xie, C. (2024b). The potential of astragalus polysaccharide for treating diabetes and its action mechanism. Front Pharmacol, 15, 1339406. DOI: https://doi.org/10.3389/fphar.2024.1339406
Liu, X., Guo, C., Yang, W., Wang, W., Diao, N., Cao, M., Cao, Y., Wang, X., Wang, X., Pei, H., Jiang, Y., Kong, M., Chen, D. (2024c). Composite microneedles loaded with Astragalus membranaceus polysaccharide nanoparticles promote wound healing by curbing the ROS/NF-kappaB pathway to regulate macrophage polarization. Carbohydr Polym, 345, 122574. DOI: https://doi.org/10.1016/j.carbpol.2024.122574
Liu, X. H., Zhao, J. B., Guo, L., Yang, Y. L., Hu, F., Zhu, R. J., Feng, S. L. (2014). Simultaneous determination of calycosin-7-O-beta-D-glucoside, ononin, calycosin, formononetin, astragaloside IV, and astragaloside II in rat plasma after oral administration of Radix Astragali extraction for their pharmacokinetic studies by ultra-pressure liquid chromatography with tandem mass spectrometry. Cell Biochem Biophys, 70(1), 677-686. DOI: https://doi.org/10.1007/s12013-014-9972-x
Liu, Y., Wu, N. (2021). Progress of nanotechnology in diabetic retinopathy Treatment. Int J Nanomedicine, 16, 1391-1403. DOI: https://doi.org/10.2147/IJN.S294807
Lu, Q. B., Ding, Y., Liu, Y., Wang, Z. C., Wu, Y. J., Niu, K. M., Li, K. X., Zhang, J. R., Sun, H. J. (2023a). Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy. J Adv Res, 51, 161-179. DOI: https://doi.org/10.1016/j.jare.2022.10.014
Lu, Y., Wang, W., Liu, J., Xie, M., Liu, Q., Li, S. (2023b). Vascular complications of diabetes: A narrative review. Medicine (Baltimore), 102(40), e35285. DOI: https://doi.org/10.1097/MD.0000000000035285
Luo, M. J., Wang, Y., Chen, S. Y., Yang, Z. M. (2022). Astragalus polysaccharides alleviate type 2 diabetic rats by reversing the expressions of sweet taste receptors and genes related to glycolipid metabolism in liver. Front Pharmacol, 13, 916603. DOI: https://doi.org/10.3389/fphar.2022.916603
Lv, L., Wu, S. Y., Wang, G. F., Zhang, J. J., Pang, J. X., Liu, Z. Q., Xu, W., Wu, S. G., Rao, J. J. (2010). Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Phytother Res, 24(2), 219-224. DOI: https://doi.org/10.1002/ptr.2915
Ma, L., La, X., Zhang, B., Xu, W., Tian, C., Fu, Q., Wang, M., Wu, C., Chen, Z., Chang, H., Li, J. A. (2023). Total Astragalus saponins can reverse type 2 diabetes mellitus-related intestinal dysbiosis and hepatic insulin resistance in vivo. Front Endocrinol (Lausanne), 14, 1190827. DOI: https://doi.org/10.3389/fendo.2023.1190827
Magliano, D. J., Boyko, E. J., 2021. IDF DIABETES ATLAS, IDF DIABETES ATLAS, 10th ed, Brussels.
Manna, P., Achari, A. E., Jain, S. K. (2017). Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys, 615, 22-34. DOI: https://doi.org/10.1016/j.abb.2017.01.002
Mao, X. Q., Wu, Y., Wu, K., Liu, M., Zhang, J. F., Zou, F., Ou-Yang, J. P. (2007). Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin, 28(12), 1947-1956. DOI: https://doi.org/10.1111/j.1745-7254.2007.00674.x
Mao, X. Q., Yu, F., Wang, N., Wu, Y., Zou, F., Wu, K., Liu, M., Ouyang, J. P. (2009). Hypoglycemic effect of polysaccharide enriched extract of Astragalus membranaceus in diet induced insulin resistant C57BL/6J mice and its potential mechanism. Phytomedicine, 16(5), 416-425. DOI: https://doi.org/10.1016/j.phymed.2008.12.011
Meizhen, Z., Xiaohui, H., Yiting, T., Yupeng, C., Puyu, H. E., Liming, Z., Bing, P., Qing, N. I. (2023). Efficacy and safety of Buyang Huanwu decoction for diabetic peripheral neuropathy: a systematic review and Metaanalysis. J Tradit Chin Med, 43(5), 841-850.
Meng, X., Liu, X., Tan, J., Sheng, Q., Zhang, D., Li, B., Zhang, J., Zhang, F., Chen, H., Cui, T., Li, M., Zhang, S. (2023). From Xiaoke to diabetes mellitus: a review of the research progress in traditional Chinese medicine for diabetes mellitus treatment. Chin Med, 18(1), 75. DOI: https://doi.org/10.1186/s13020-023-00783-z
Meng, Y., Zhang, Y., Jia, N., Qiao, H., Zhu, M., Meng, Q., Lu, Q., Zu, Y. (2018). Synthesis and evaluation of a novel water-soluble high Se-enriched Astragalus polysaccharide nanoparticles. Int J Biol Macromol, 118(Pt B), 1438-1448. DOI: https://doi.org/10.1016/j.ijbiomac.2018.06.153
Mohammad, G., Kowluru, R. A. (2022). Mitochondrial dynamics in the metabolic memory of diabetic retinopathy. J Diabetes Res, 2022, 3555889. DOI: https://doi.org/10.1155/2022/3555889
Montaigne, D., Butruille, L., Staels, B. (2021). PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol, 18(12), 809-823. DOI: https://doi.org/10.1038/s41569-021-00569-6
Motomura, K., Fujiwara, Y., Kiyota, N., Tsurushima, K., Takeya, M., Nohara, T., Nagai, R., Ikeda, T. (2009). Astragalosides isolated from the root of astragalus radix inhibit the formation of advanced glycation end products. J Agric Food Chem, 57(17), 7666-7672. DOI: https://doi.org/10.1021/jf9007168
Muraleedharan, R., Dasgupta, B. (2022). AMPK in the brain: its roles in glucose and neural metabolism. FEBS J, 289(8), 2247-2262. DOI: https://doi.org/10.1111/febs.16151
Murata, N., Nishimura, K., Harada, N., Kitakaze, T., Yoshihara, E., Inui, H., Yamaji, R. (2024). Insulin reduces endoplasmic reticulum stress-induced apoptosis by decreasing mitochondrial hyperpolarization and caspase-12 in INS-1 pancreatic beta-cells. Physiol Rep, 12(12), e16106. DOI: https://doi.org/10.14814/phy2.16106
Peng, C., Li, J., Ke, X., Liu, F., Huang, K. E. (2023). In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD. Ann Med, 55(1), 2200258. DOI: https://doi.org/10.1080/07853890.2023.2200258
Peng, Q. H., Tong, P., Gu, L. M., Li, W. J. (2020). Astragalus polysaccharide attenuates metabolic memory-triggered ER stress and apoptosis via regulation of miR-204/SIRT1 axis in retinal pigment epithelial cells. Biosci Rep, 40(1), BSR20192121. DOI: https://doi.org/10.1042/BSR20192121
Qing, L. S., Chen, T. B., Sun, W. X., Chen, L., Luo, P., Zhang, Z. F., Ding, L. S. (2019). Pharmacokinetics comparison, intestinal absorption and acute toxicity assessment of a novel water-soluble astragaloside IV derivative (astragalosidic acid, LS-102). Eur J Drug Metab Pharmacokinet, 44(2), 251-259. DOI: https://doi.org/10.1007/s13318-018-0515-5
Qu, C., Tan, X., Hu, Q., Tang, J., Wang, Y., He, C., He, Z., Li, B., Fu, X., Du, Q. (2024). A systematic review of astragaloside IV effects on animal models of diabetes mellitus and its complications. Heliyon, 10(5), e26863. DOI: https://doi.org/10.1016/j.heliyon.2024.e26863
Richter, A., Lerner, S., Schroppel, B. (2011). Current state of combined kidney and pancreas transplantation. Blood Purif, 31(1-3), 96-101. DOI: https://doi.org/10.1159/000321865
Saikia, R., Joseph, J. (2021). AMPK: a key regulator of energy stress and calcium-induced autophagy. J Mol Med (Berl), 99(11), 1539-1551. DOI: https://doi.org/10.1007/s00109-021-02125-8
Salehi, B., Carneiro, J. N. P., Rocha, J. E., Coutinho, H. D. M., Morais Braga, M. F. B., Sharifi-Rad, J., Semwal, P., Painuli, S., Moujir, L. M., de Zarate Machado, V., Janakiram, S., Anil Kumar, N. V., Martorell, M., Cruz-Martins, N., El Beyrouthy, M., Sadaka, C. (2021). Astragalus species: Insights on its chemical composition toward pharmacological applications. Phytother Res, 35(5), 2445-2476. DOI: https://doi.org/10.1002/ptr.6974
Salm, S., Rutz, J., van den Akker, M., Blaheta, R. A., Bachmeier, B. E. (2023). Current state of research on the clinical benefits of herbal medicines for non-life-threatening ailments. Front Pharmacol, 14, 1234701. DOI: https://doi.org/10.3389/fphar.2023.1234701
Schratter, M., Lass, A., Radner, F. P. W. (2022). ABHD5-A regulator of lipid metabolism essential for diverse cellular functions. Metabolites, 12(11), 1015. DOI: https://doi.org/10.3390/metabo12111015
Sha, W., Zhao, B., Wei, H., Yang, Y., Yin, H., Gao, J., Zhao, W., Kong, W., Ge, G., Lei, T. (2023). Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway. Phytomedicine, 112, 154667. DOI: https://doi.org/10.1016/j.phymed.2023.154667
Shan, X. M., Chen, C. W., Zou, D. W., Gao, Y. B., Ba, Y. Y., He, J. X., Zhu, Z. Y., Liang, J. J. (2024). Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury. Chin Med, 19(1), 151. DOI: https://doi.org/10.1186/s13020-024-01007-8
Shan, X. M., Lu, C., Chen, C. W., Wang, C. T., Liu, T. T., An, T., Zhu, Z. Y., Zou, D. W., Gao, Y. B. (2025). Tangshenning formula alleviates tubular injury in diabetic kidney disease via the Sestrin2/AMPK/PGC-1alpha axis: Restoration of mitochondrial function and inhibition of ferroptosis. J Ethnopharmacol, 345, 119579. DOI: https://doi.org/10.1016/j.jep.2025.119579
Shi, J., Zheng, L., Lin, Z., Hou, C., Liu, W., Yan, T., Zhu, L., Wang, Y., Lu, L., Liu, Z. (2015). Study of pharmacokinetic profiles and characteristics of active components and their metabolites in rat plasma following oral administration of the water extract of Astragali radix using UPLC-MS/MS. J Ethnopharmacol, 169, 183-194. DOI: https://doi.org/10.1016/j.jep.2015.04.019
Shrestha, M. M., Lim, C. Y., Bi, X., Robinson, R. C., Han, W. (2021). Tmod3 phosphorylation mediates AMPK-dependent GLUT4 plasma membrane insertion in myoblasts. Front Endocrinol (Lausanne), 12, 653557. DOI: https://doi.org/10.3389/fendo.2021.653557
Silva, M. L., Bernardo, M. A., Singh, J., de Mesquita, M. F. (2022). Cinnamon as a complementary therapeutic approach for dysglycemia and dyslipidemia control in type 2 diabetes mellitus and its molecular mechanism of action: A review. Nutrients, 14(13), 2773. DOI: https://doi.org/10.3390/nu14132773
Song, J., Lee, D., Min, B., Bae, J. S., Chang, G. T., Kim, H. (2017). Safety evaluation of Astragalus extract mixture HT042 and its constituent herbs in Sprague-Dawley rats. Phytomedicine, 32, 59-67. DOI: https://doi.org/10.1016/j.phymed.2017.03.005
Song, Q., Cheng, S. W., Li, D., Cheng, H., Lai, Y. S., Han, Q., Wu, H. Y., Shaw, P. C., Zuo, Z. (2022). Gut microbiota mediated hypoglycemic effect of Astragalus membranaceus polysaccharides in db/db mice. Front Pharmacol, 13, 1043527. DOI: https://doi.org/10.3389/fphar.2022.1043527
Song, Q., Zou, J., Li, D., Cheng, S. W., Li, K. L. S., Yang, X., Shaw, P. C., Zuo, Z. (2024). Gastrointestinal metabolism of Astragalus membranaceus polysaccharides and its related hypoglycemic mechanism based on gut microbial transformation. Int J Biol Macromol, 280(Pt 3), 135847. DOI: https://doi.org/10.1016/j.ijbiomac.2024.135847
Stambolov, I., Shkondrov, A., Kunert, O., Bucar, F., Kondeva-Burdina, M., Krasteva, I. (2023). Cycloartane saponins from Astragalus glycyphyllos and their in vitro neuroprotective, antioxidant, and hMAO-B-inhibiting effects. Metabolites, 13(7), 857. DOI: https://doi.org/10.3390/metabo13070857
Su, J., Gao, C., Xie, L., Fan, Y., Shen, Y., Huang, Q., Wang, N., Xu, Y., Yang, N., Gui, D. (2021). Astragaloside II ameliorated podocyte injury and mitochondrial dysfunction in streptozotocin-induced diabetic rats. Front Pharmacol, 12, 638422. DOI: https://doi.org/10.3389/fphar.2021.638422
Su, M., Tang, T., Tang, W., Long, Y., Wang, L., Liu, M. (2023). Astragalus improves intestinal barrier function and immunity by acting on intestinal microbiota to treat T2DM: a research review. Front Immunol, 14, 1243834. DOI: https://doi.org/10.3389/fimmu.2023.1243834
Su, P. P., Liu, D. W., Zhou, S. J., Chen, H., Wu, X. M., Liu, Z. S. (2022). Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy. Mil Med Res, 9(1), 23. DOI: https://doi.org/10.1186/s40779-022-00385-0
Sun, S., Yang, S., An, N., Wang, G., Xu, Q., Liu, J., Mao, Y. (2019). Astragalus polysaccharides inhibits cardiomyocyte apoptosis during diabetic cardiomyopathy via the endoplasmic reticulum stress pathway. J Ethnopharmacol, 238, 111857. DOI: https://doi.org/10.1016/j.jep.2019.111857
Sun, S., Yang, S., Zhang, N., Yu, C., Liu, J., Feng, W., Xu, W., Mao, Y. (2023). Astragalus polysaccharides alleviates cardiac hypertrophy in diabetic cardiomyopathy via inhibiting the BMP10-mediated signaling pathway. Phytomedicine, 109, 154543. DOI: https://doi.org/10.1016/j.phymed.2022.154543
Sun, Y., Dinenno, F. A., Tang, P., Kontaridis, M. I. (2024). Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics. Front Cardiovasc Med, 11, 1445739. DOI: https://doi.org/10.3389/fcvm.2024.1445739
Tan, T. E., Wong, T. Y. (2022). Diabetic retinopathy: Looking forward to 2030. Front Endocrinol (Lausanne), 13, 1077669. DOI: https://doi.org/10.3389/fendo.2022.1077669
Tanase, D. M., Gosav, E. M., Neculae, E., Costea, C. F., Ciocoiu, M., Hurjui, L. L., Tarniceriu, C. C., Maranduca, M. A., Lacatusu, C. M., Floria, M., Serban, I. L. (2020). Role of gut microbiota on onset and progression of microvascular complications of type 2 diabetes (T2DM). Nutrients, 12(12), 3719. DOI: https://doi.org/10.3390/nu12123719
Tang, S., Ye, J. X., Li, R. Y., Wang, J. L., Xie, H. C., Zhang, Y. Q., Wang, M., Sun, G. B. (2025). Formononetin attenuates myocardial ischemia/reperfusion injury by regulating neutrophil extracellular traps formation and platelet activation via platelet CD36. Phytomedicine, 141, 156736. DOI: https://doi.org/10.1016/j.phymed.2025.156736
Tang, X., Li, X., Zhang, D., Han, W. (2022). Astragaloside-IV alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2. Bioengineered, 13(4), 8240-8254. DOI: https://doi.org/10.1080/21655979.2022.2049471
Tonade, D., Kern, T. S. (2021). Photoreceptor cells and RPE contribute to the development of diabetic retinopathy. Prog Retin Eye Res, 83, 100919. DOI: https://doi.org/10.1016/j.preteyeres.2020.100919
Wang, D., Li, J., Luo, G., Zhou, J., Wang, N., Wang, S., Zhao, R., Cao, X., Ma, Y., Liu, G., Hao, L. (2023a). Nox4 as a novel therapeutic target for diabetic vascular complications. Redox Biol, 64, 102781. DOI: https://doi.org/10.1016/j.redox.2023.102781
Wang, L., Liu, C., Wang, L., Tang, B. (2023b). Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62/Keap1/Nrf2 pathway-mediated ferroptosis. Eur J Pharmacol, 944, 175516. DOI: https://doi.org/10.1016/j.ejphar.2023.175516
Wang, N., Zhang, D., Mao, X., Zou, F., Jin, H., Ouyang, J. (2009). Astragalus polysaccharides decreased the expression of PTP1B through relieving ER stress induced activation of ATF6 in a rat model of type 2 diabetes. Mol Cell Endocrinol, 307(1-2), 89-98. DOI: https://doi.org/10.1016/j.mce.2009.03.001
Wang, S., Duan, J., Liao, J., Wang, Y., Xiao, X., Li, L., Liu, Y., Gu, H., Yang, P., Fu, D., Du, J., Li, X., Shao, M. (2022). LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis. Aging (Albany NY), 14(16), 6809-6828. DOI: https://doi.org/10.18632/aging.204256
Wang, T., Zhang, Z., Song, C., Sun, L., Sui, X., Qu, Q., Liu, J. (2020). Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR‑128 expression in diabetic rats. Int J Mol Med, 46(1), 340-350. DOI: https://doi.org/10.3892/ijmm.2020.4588
Wang, X., Sun, H., Yu, H., Du, B., Fan, Q., Jia, B., Zhang, Z. (2024a). Bone morphogenetic protein 10, a rising star in the field of diabetes and cardiovascular disease. J Cell Mol Med, 28(10), e18324. DOI: https://doi.org/10.1111/jcmm.18324
Wang, Y., Qin, Y., Kang, Q., Wang, H., Zhou, S., Wu, Y., Liu, Y., Su, Y., Guo, Y., Xiu, M., He, J. (2024b). Therapeutic potential of Astragalus membranaceus-Pueraria lobata decoction for the treatment of chemotherapy bowel injury. FASEB J, 38(19), e70102. DOI: https://doi.org/10.1096/fj.202401677R
Wang, Z., Li, X. L., Hong, K. F., Zhao, T. T., Dong, R. X., Wang, W. M., Li, Y. T., Zhang, G. L., Lin, J., Gui, D. K., Xu, Y. H. (2021). Total flavonoids of astragalus ameliorated bile acid metabolism dysfunction in diabetes mellitus. Evid Based Complement Alternat Med, 2021, 6675567. DOI: https://doi.org/10.1155/2021/6675567
Wei, Y., Wu, Y., Feng, K., Zhao, Y., Tao, R., Xu, H., Tang, Y. (2020). Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-beta/Smads pathway. J Ethnopharmacol, 249, 112404. DOI: https://doi.org/10.1016/j.jep.2019.112404
Wei, Z., Weng, S., Wang, L., Mao, Z. (2018). Mechanism of Astragalus polysaccharides in attenuating insulin resistance in Rats with type 2 diabetes mellitus via the regulation of liver microRNA‑203a‑3p. Mol Med Rep, 17(1), 1617-1624. DOI: https://doi.org/10.3892/mmr.2017.8084
Wu, S., Zou, M. H. (2020). AMPK, mitochondrial function, and cardiovascular disease. Int J Mol Sci, 21(14), 4987. DOI: https://doi.org/10.3390/ijms21144987
Wu, Y., Ou-Yang, J. P., Wu, K., Wang, Y., Zhou, Y. F., Wen, C. Y. (2005). Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B. Acta Pharmacol Sin, 26(3), 345-352. DOI: https://doi.org/10.1111/j.1745-7254.2005.00062.x
Xia, H., He, W., Lv, C., Zhang, J., Lin, X., Qin, S. (2025). The inhibitory effect of Astragalus flavone extract on hyperuricemia and its underlying molecular mechanism by targeting JNK/AP-1/NLRP3/IL-1beta signaling pathway. Phytomedicine, 140, 156622. DOI: https://doi.org/10.1016/j.phymed.2025.156622
Xia, S., Duan, W., Liu, W., Zhang, X., Wang, Q. (2021). GRP78 in lung cancer. J Transl Med, 19(1), 118. DOI: https://doi.org/10.1186/s12967-021-02786-6
Xu, G., Yuan, H., Liu, J., Wang, X., Ma, L., Wang, Y., Dong, G. (2025). Astragalus mongholicus polysaccharides alleviate kidney injury in rats with type 2 diabetes through modulation of oxidation, inflammation, and gut microbiota. Int J Mol Sci, 26(4), 1470. DOI: https://doi.org/10.3390/ijms26041470
Xu, J., Shan, X., Chen, C., Gao, Y., Zou, D., Wang, X., Wang, T., Shi, Y. (2022). Tangshenning attenuates high glucose-induced podocyte injury via restoring autophagy activity through inhibiting mTORC1 activation. J Diabetes Res, 2022, 1610416. DOI: https://doi.org/10.1155/2022/1610416
Xu, Y., Xiong, J., Zhao, Y., He, B., Zheng, Z., Chu, G., Zhu, Q. (2015). Calycosin rebalances advanced glycation end products-induced glucose uptake dysfunction of hepatocyte in vitro. Am J Chin Med, 43(6), 1191-1210. DOI: https://doi.org/10.1142/S0192415X15500688
Xu, Y., Xu, C., Huang, J., Xu, C., Xiong, Y. (2024). Astragalus polysaccharide attenuates diabetic nephropathy by reducing apoptosis and enhancing autophagy through activation of Sirt1/FoxO1 pathway. Int Urol Nephrol, 56(9), 3067-3078. DOI: https://doi.org/10.1007/s11255-024-04038-0
Xue, H. Z., Chen, Y., Wang, S. D., Yang, Y. M., Cai, L. Q., Zhao, J. X., Huang, W. J., Xiao, Y. H. (2024). Radix astragali and its representative extracts for diabetic nephropathy: Efficacy and molecular mechanism. J Diabetes Res, 2024, 5216113. DOI: https://doi.org/10.1155/2024/5216113
Xuying, W., Jiangbo, Z., Yuping, Z., Xili, M., Yiwen, Z., Tianbao, Z., Weidong, Z. (2010). Effect of astragaloside IV on the general and peripartum reproductive toxicity in Sprague-Dawley rats. Int J Toxicol, 29(5), 505-516. DOI: https://doi.org/10.1177/1091581810376840
Yakubogullari, N., Cagir, A., Bedir, E., Sag, D. (2023). Astragalus saponins, astragaloside VII and newly synthesized derivatives, induce dendritic cell maturation and T cell activation. Vaccines (Basel), 11(3), 495. DOI: https://doi.org/10.3390/vaccines11030495
Yang, C., Pan, Q., Ji, K., Tian, Z., Zhou, H., Li, S., Luo, C., Li, J. (2023). Review on the protective mechanism of astragaloside IV against cardiovascular diseases. Front Pharmacol, 14, 1187910. DOI: https://doi.org/10.3389/fphar.2023.1187910
Yang, L., Jiang, Y., Zhang, Z., Hou, J., Tian, S., Liu, Y. (2020). The anti-diabetic activity of licorice, a widely used Chinese herb. J Ethnopharmacol, 263, 113216. DOI: https://doi.org/10.1016/j.jep.2020.113216
Yeh, T. S., Chuang, H. L., Huang, W. C., Chen, Y. M., Huang, C. C., Hsu, M. C. (2014). Astragalus membranaceus improves exercise performance and ameliorates exercise-induced fatigue in trained mice. Molecules, 19(3), 2793-2807. DOI: https://doi.org/10.3390/molecules19032793
Yin, X., Zhang, Y., Yu, J., Zhang, P., Shen, J., Qiu, J., Wu, H., Zhu, X. (2006). The antioxidative effects of astragalus saponin I protect against development of early diabetic nephropathy. J Pharmacol Sci, 101(2), 166-173. DOI: https://doi.org/10.1254/jphs.FP0050041
Yin, Y., Qu, H., Yang, Q., Fang, Z., Gao, R. (2021). Astragaloside IV alleviates Schwann cell injury in diabetic peripheral neuropathy by regulating microRNA-155-mediated autophagy. Phytomedicine, 92, 153749. DOI: https://doi.org/10.1016/j.phymed.2021.153749
Yu, S. Y., Ouyang, H. T., Yang, J. Y., Huang, X. L., Yang, T., Duan, J. P., Cheng, J. P., Chen, Y. X., Yang, Y. J., Qiong, P. (2007). Subchronic toxicity studies of Radix Astragali extract in rats and dogs. J Ethnopharmacol, 110(2), 352-355. DOI: https://doi.org/10.1016/j.jep.2006.09.024
Yu, W., Wang, Y., Jiang, D., Shang, J., Liu, M., Efferth, T., Teng, C. B. (2022). A saponin from astragalus promotes pancreatic ductal organoids differentiation into insulin-producing cells. Phytomedicine, 102, 154190. DOI: https://doi.org/10.1016/j.phymed.2022.154190
Zeng, Y., Li, Y., Jiang, W., Hou, N. (2024). Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy. Front Cardiovasc Med, 11, 1375400. DOI: https://doi.org/10.3389/fcvm.2024.1375400
Zeng, Y., Zheng, Z., Liu, F., Yi, G. (2021). Circular RNAs in metabolism and metabolic disorders. Obes Rev, 22(7), e13220. DOI: https://doi.org/10.1111/obr.13220
Zhang, J., Lu, M., Li, C., Yan, B., Xu, F., Wang, H., Zhang, Y., Yang, Y. (2024a). Astragaloside IV mitigates hypoxia-induced cardiac hypertrophy through calpain-1-mediated mTOR activation. Phytomedicine, 125, 155250. DOI: https://doi.org/10.1016/j.phymed.2023.155250
Zhang, J., Wu, C., Gao, L., Du, G., Qin, X. (2020). Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects. Adv Pharmacol, 87, 89-112. DOI: https://doi.org/10.1016/bs.apha.2019.08.002
Zhang, J. J., Wang, W. L., Zhong, J. T., Sun, H. M., Jiang, Y. C., Shang, Y., Song, J. (2025). Calycosin limits hepatic fibrogenesis via KLF15 dependent repression of P2X7R in thioacetamide-induced hepatic fibrosis. J Ethnopharmacol, 120194. DOI: https://doi.org/10.1016/j.jep.2025.120194
Zhang, L., Shi, J., Shen, Q., Fu, Y., Qi, S., Wu, J., Chen, J., Zhang, H., Mu, Y., Chen, G., Liu, P., Liu, W. (2024b). Astragalus saponins protect against extrahepatic and intrahepatic cholestatic liver fibrosis models by activation of farnesoid X receptor. J Ethnopharmacol, 318(Pt A), 116833. DOI: https://doi.org/10.1016/j.jep.2023.116833
Zhang, M., Guo, C., Li, Z., Cai, X., Wen, X., Lv, F., Lin, C., Ji, L. (2024c). Mulberry Twig Alkaloids improved the progression of metabolic-associated fatty liver disease in high-fat diet-induced obese mice by regulating the PGC1alpha/PPARalpha and KEAP1/NRF2 pathways. Pharmaceuticals (Basel), 17(10), 1287. DOI: https://doi.org/10.3390/ph17101287
Zhang, M., Sui, W., Xing, Y., Cheng, J., Cheng, C., Xue, F., Zhang, J., Wang, X., Zhang, C., Hao, P., Zhang, Y. (2021a). Angiotensin IV attenuates diabetic cardiomyopathy via suppressing FoxO1-induced excessive autophagy, apoptosis and fibrosis. Theranostics, 11(18), 8624-8639. DOI: https://doi.org/10.7150/thno.48561
Zhang, Q., Zhu, L. L., Chen, G. G., Du, Y. (2007a). Pharmacokinetics of astragaloside iv in beagle dogs. Eur J Drug Metab Pharmacokinet, 32(2), 75-79. DOI: https://doi.org/10.1007/BF03190995
Zhang, R., Qin, X., Zhang, T., Li, Q., Zhang, J., Zhao, J. (2018). Astragalus polysaccharide improves insulin sensitivity via AMPK activation in 3T3-L1 adipocytes. Molecules, 23(10), 2711. DOI: https://doi.org/10.3390/molecules23102711
Zhang, R. H., Cao, S. S., Shi, Y., Wang, X., Shi, L. L., Zhang, Y. H., Han, C. J., Wang, B., Feng, L., Liu, J. P. (2023). Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment. Naunyn Schmiedebergs Arch Pharmacol, 396(10), 2637-2650. DOI: https://doi.org/10.1007/s00210-023-02486-6
Zhang, S. X., Wang, J. J., Starr, C. R., Lee, E. J., Park, K. S., Zhylkibayev, A., Medina, A., Lin, J. H., Gorbatyuk, M. (2024d). The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease. Prog Retin Eye Res, 98, 101231. DOI: https://doi.org/10.1016/j.preteyeres.2023.101231
Zhang, W. D., Zhang, C., Liu, R. H., Li, H. L., Zhang, J. T., Mao, C., Moran, S., Chen, C. L. (2006). Preclinical pharmacokinetics and tissue distribution of a natural cardioprotective agent astragaloside IV in rats and dogs. Life Sci, 79(8), 808-815. DOI: https://doi.org/10.1016/j.lfs.2006.02.032
Zhang, X., Jia, L., Ma, Q., Zhang, X., Chen, M., Liu, F., Zhang, T., Jia, W., Zhu, L., Qi, W., Wang, N. (2024e). Astragalus polysaccharide modulates the gut microbiota and metabolites of patients with type 2 diabetes in an in vitro fermentation model. Nutrients, 16(11), 1698. DOI: https://doi.org/10.3390/nu16111698
Zhang, X., Wang, J., Xiang, S., Zhao, L., Lv, M., Duan, Y., Gao, G., Wang, P., Jie Chen, J., Xu, J., Xie, Z., Zhang, Z. (2024f). Astragaloside I from astragalus attenuates diabetic kidney disease by regulating HDAC3/Klotho/TGF-beta1 loop. Am J Chin Med, 52(6), 1795-1817. DOI: https://doi.org/10.1142/S0192415X24500708
Zhang, X., Yang, X., Sun, B., Zhu, C. (2021b). Perspectives of glycemic variability in diabetic neuropathy: a comprehensive review. Commun Biol, 4(1), 1366. DOI: https://doi.org/10.1038/s42003-021-02896-3
Zhang, X., Zhong, G., Jiang, C., Ha, X., Yang, Q., Wu, H. (2024g). Exploring the potential anti-diabetic peripheral neuropathy mechanisms of Huangqi Guizhi Wuwu Decoction by network pharmacology and molecular docking. Metab Brain Dis, 40(1), 20. DOI: https://doi.org/10.1007/s11011-024-01474-w
Zhang, Y. W., Wu, C. Y., Cheng, J. T. (2007b). Merit of Astragalus polysaccharide in the improvement of early diabetic nephropathy with an effect on mRNA expressions of NF-kappaB and IkappaB in renal cortex of streptozotoxin-induced diabetic rats. J Ethnopharmacol, 114(3), 387-392. DOI: https://doi.org/10.1016/j.jep.2007.08.024
Zhang, Y. Y., Tan, R. Z., Zhang, X. Q., Yu, Y., Yu, C. (2019a). Calycosin ameliorates diabetes-induced renal inflammation via the NF-kappaB pathway in vitro and in vivo. Med Sci Monit, 25, 1671-1678. DOI: https://doi.org/10.12659/MSM.915242
Zhang, Z., Zhang, L., Xu, H. (2019b). Effect of Astragalus polysaccharide in treatment of diabetes mellitus: a narrative review. J Tradit Chin Med, 39(1), 133-138.
Zhao, B., Zhang, X., Han, W., Cheng, J., Qin, Y. (2017). Wound healing effect of an Astragalus membranaceus polysaccharide and its mechanism. Mol Med Rep, 15(6), 4077-4083. DOI: https://doi.org/10.3892/mmr.2017.6488
Zhen, Z., Wei, S., Yunfei, W., Jie, X., Jienan, X., Yiting, S., Wen, X., Shuyu, G., Yue, L., Xuanyu, W., Yumei, Z., Huafa, Q. (2024). Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the beta-catenin/ NF-kappaB axis at the late phase of wound-healing. Heliyon, 10(4), e24644. DOI: https://doi.org/10.1016/j.heliyon.2024.e24644
Zheng, H., Wan, J., Shan, Y., Song, X., Jin, J., Su, Q., Chen, S., Lu, X., Yang, J., Li, Q., Song, Y., Li, B. (2021). MicroRNA-185-5p inhibits hepatic gluconeogenesis and reduces fasting blood glucose levels by suppressing G6Pase. Theranostics, 11(16), 7829-7843. DOI: https://doi.org/10.7150/thno.46882
Zhou, W., Ren, S., Lu, Y., Wang, Y., Feng, L., Gao, Q. (2024). Specific knockout of Notch-1 in macrophages modulate the progression of hepatic insulin resistance in HFD fed mice via regulating IRE1alpha-XBP1 signals. J Coll Physicians Surg Pak, 34(5), 527-532. DOI: https://doi.org/10.29271/jcpsp.2024.05.527
Zhu, Y., Su, Y., Zhang, J., Zhang, Y., Li, Y., Han, Y., Dong, X., Li, W., Li, W. (2021). Astragaloside IV alleviates liver injury in type 2 diabetes due to promotion of AMPK/mTOR‑mediated autophagy. Mol Med Rep, 23(6), 437. DOI: https://doi.org/10.3892/mmr.2021.12076
Zou, F., Mao, X. Q., Wang, N., Liu, J., Ou-Yang, J. P. (2009). Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin, 30(12), 1607-1615. DOI: https://doi.org/10.1038/aps.2009.168
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