Astragalus membranaceus (Radix Astragali or “Huang Qi”) is an herb whose root has a long history of use in Chinese herbal medicine to treat a wide variety of disorders. The major active components are polysaccharides, flavonoids, saponins, and glycoproteins. 

      Modern use of astragalus has focused on its immunomodulating, antioxidant, and anti-inflammatory effects, for which it has been actively investigated. Additionally, astragalus-based treatments have been shown to lessen the toxicity of immunosuppressants and other chemotherapeutics1. 

      Active astragalus compounds have been shown to prevent the onset2 and alleviate severity of disease in animal models of MS (3-6. Mechanisms include (but are not limited to):

• Protecting the blood-brain barrier from attack by offending toxins2

• Inhibiting inflammatory mediators in microglia (primary immune effector cells of the CNS) in the spinal cord and brain5 

• Inhibiting proliferation of cells that attack the CNS7, including myelin oligodendrocyte glycoprotein (important in the myelination of nerves in the CNS)3,8

• Increasing Treg cells and Foxp38.

• Counterbalancing oxidative stress by reduction of free radical levels, enhancement of antioxidant defenses, and increase of anti-apoptotic and anti-inflammatory pathways7

      Astragalus polysaccharides have been shown to both prevent demyelination8,9 and facilitate remyelination, relieving associated neurological dysfunction. 

      The dose applied in these studies has been 1-50 mg/kg, depending on the specific extract2,4,10.

      Caution has been recommended for use of a major Astragalus membranaceus component –astragaloside IV – in pregnancy. When tested in rats and rabbits, intravenous administration of 0.25 mg/kg and above was found to be toxic to both mother and fetus, though no birth defects were found among surviving offspring11.

      More recently, astragaloside IV from Astragalus membranaceus administered to the stomach at a dose of 15 mg/kg was associated with improved outcomes in an animal model of gestational diabetes12,13, in part by markedly lowering inflammation. A higher dose of 30 mg/kg was found to be toxic to mother and fetus13. 

      In the context of pregnancy in autoimmunity, Astragalus membranaceus was tested in an animal model of systemic lupus erythematosus, which was induced in mice by application of lipopolysaccharide, known to cause inflammatory reactions in humans as well. Astragalus solution of 1 g/ml was provided directly into the stomach for a month. Compared to control (water), treatment improved the conception rate and increased the number and average weight of fetuses in the lupus mice. It also improved kidney function, which is known to decrease in the disease. Most relevant to autoimmune disorders in general, astragalus treatment reduced the ratio of autoimmune cells and the levels of inflammatory compounds in the body. No toxicity of the astragalus was observed14. 

It is important to use the noted species, Astragalus membranaceus, as other species of astragalus (e.g., Astragalus mollissimus, Astragalus lentiginosus) have been linked to birth defects15.

      Astragalus has been purported to enhance breastmilk production; however, no scientifically valid clinical trials support this use. No data exist on the excretion of any components of astragalus into breastmilk or on the safety and efficacy of astragalus in nursing mothers or infants16.

References

1. Auyeung KK, Han QB, Ko JK. Astragalus membranaceus: A Review of its Protection Against Inflammation and Gastrointestinal Cancers. Am J Chin Med. 2016;44(1):1-22. doi:10.1142/S0192415X16500014

2. Li H, Wang P, Huang F, et al. Astragaloside IV protects blood-brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice. Toxicol Appl Pharmacol. Feb 1 2018;340:58-66. doi:10.1016/j.taap.2017.12.019

3. Sun Y, Jing Y, Huang M, et al. The PD-1/PD-Ls pathway is up-regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides. J Neuroimmunol. Jul 15 2019;332:78-90. doi:10.1016/j.jneuroim.2019.03.019

4. Xing Y, Liu B, Zhao Y, et al. Immunomodulatory and neuroprotective mechanisms of Huangqi glycoprotein treatment in experimental autoimmune encephalomyelitis. Folia Neuropathol. 2019;57(2):117-128. doi:10.5114/fn.2019.85843

5. Yang L, Han X, Xing F, et al. Total flavonoids of astragalus attenuates experimental autoimmune encephalomyelitis by suppressing the activation and inflammatory responses of microglia via JNK/AKT/NFkappaB signaling pathway. Phytomedicine. Jan 2021;80:153385. doi:10.1016/j.phymed.2020.153385

6. 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. May 15 2020;249:117448. doi:10.1016/j.lfs.2020.117448

7. He Y, Du M, Gao Y, et al. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels. PLoS One. 2013;8(10):e76495. doi:10.1371/journal.pone.0076495

8. Yang L, Xing F, Han X, et al. Astragaloside IV regulates differentiation and induces apoptosis of activated CD4(+) T cells in the pathogenesis of experimental autoimmune encephalomyelitis. Toxicol Appl Pharmacol. Jan 1 2019;362:105-115. doi:10.1016/j.taap.2018.10.024

9. Ye N, Cruz J, Peng X, Ma J, Zhang A, Cheng X. Remyelination is enhanced by Astragalus polysaccharides through inducing the differentiation of oligodendrocytes from neural stem cells in cuprizone model of demyelination. Brain Res. Jul 15 2021;1763:147459. doi:10.1016/j.brainres.2021.147459

10. Yang Y, Hozawa A, Kogure M, et al. Dietary Inflammatory Index Positively Associated With High-Sensitivity C-Reactive Protein Level in Japanese From NIPPON DATA2010. J Epidemiol. Feb 5 2020;30(2):98-107. doi:10.2188/jea.JE20180156

11. Jiangbo Z, Xuying W, Yuping Z, Xili M, Yiwen Z, Tianbao Z. Effect of astragaloside IV on the embryo-fetal development of Sprague-Dawley rats and New Zealand White rabbits. J Appl Toxicol. Jul 2009;29(5):381-5. doi:10.1002/jat.1422

12. Zhang R, Xing B, Zhao J, et al. Astragaloside IV relieves gestational diabetes mellitus in genetic mice through reducing hepatic gluconeogenesis. Can J Physiol Pharmacol. Jul 2020;98(7):466-472. doi:10.1139/cjpp-2019-0548

13. Zhang R, Zhang X, Xing B, et al. Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice. Reprod Biol Endocrinol. Sep 26 2019;17(1):77. doi:10.1186/s12958-019-0522-7

14. Chen HQ, Zhang N, Li CX, Zhang HX. Effects of Astragalus membranaceus on systemic lupus erythematosus in a mouse model of pregnancy. Immun Inflamm Dis. Jun 2022;10(6):e624. doi:10.1002/iid3.624

15. Chamorro-Cevallos G, Mojica-Villegas MA, Garcia-Martinez Y, et al. A Complete Review of Mexican Plants with Teratogenic Effects. Plants (Basel). Jun 24 2022;11(13)doi:10.3390/plants11131675

16. Astragalus. Drugs and Lactation Database (LactMed(R)). 2006.