ASTRAGALUS

BACKGROUND

Ingredient type: Botanical, Extract

Also Known As: Astragalus membranaceous, Milk vetch, Huang qi, Chinese milkvetch

Astragalus membranaceus is part of the Fabaceae (legumes, peas, beans) family and is considered a sweet and nourishing herb foundational to Traditional Chinese Medicine (TCM). For hundreds of years, the Chinese have used astragalus to support the immune system as well as strengthen Wei Qi (Chi). According to TCM, A. membranaceus is said to help tonify the spleen, thus being generally supportive and strengthening the body (17).

TRADITIONAL USES

“It is in great repute as a tonic, pectoral, and diuretic medicine, the disease for which it is prescribed, therefore are almost numberless.” – G.A. Stuart, Chinese Materia Medica, 1911.

In China, A. membranaceus is known as Huang Qi, Yellow Leader. The plant was given this name due to the color of the root’s interior and the plant’s value and prestige, as seen by the Chinese medical practitioners. A consensus points to A. membranaceus being used amongst the Chinese for at least 2,000 years. Today in TCM, astragalus is still considered one of the top, fundamentally utilized herbs. Historically it was consumed as a tonic or tea to help speed up the healing process after illness (1).

WHAT DOES SCIENCE TELL US?

Astragalus Might Support a Healthy Immune System:

In one double-blind, randomized pilot study, the effects of Echinacea purpurea, Astragalus membranaceus, and Glycyrrhiza glabra were assessed on their ability to activate the immune cell function (CD4, CD8, CD25, CD69). The herbs in this study were administered in a liquid form singly and in combination with one another to assessed the difference. Over seven days, A. membranaceus was noted to exhibit immune system activation through specific immune cell activation. Of the three herbs assessed in this study, A. membranaceus was most effective at modulating the immune system (2).

In another study, bioactive fractions were isolated from the root of A. membranaceus (AI) and administered in mouse models to test the effects of specific and nonspecific immunity. The results showed that AI exhibited mitogenic and co-mitogenic activity in vitro and in vivo in mouse splenocyte cells. Conducted experiments also demonstrated that AI was also active upon administration of human lymphocytes. According to the study, intraperitoneal injection of AI into mice markedly augmented the antibody response to sheep red blood cells” as well. There was a resulting influx of macrophages into the peritoneal cavity along with a more considerable increase in phagocytic activity amongst the macrophages. Upon assessing the overall results of this study, it was concluded that certain components of A. membranaceus have potential immunomodulating and immune-restorative effects, both in vitro and in vivo (3).

One study was conducted to investigate the effects of Astragalus polysaccharides (APS) on tumor necrosis factor (TNF)-a-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs). In the study, the HUVECs were treated with TNF-a for 24 hours. The amounts of intercellular adhesion, vascular adhesion, HUVEC viability, and reactive oxygen species production were measured in this study. Upon analysis of the results, it was noted that APS caused increases of ICAM-1 and VCAM-1 expression along with a decrease in apoptosis, ROS production, and adhesion function damage. The concluding results suggest that APS could potentially be used to treat and prevent certain endothelial cell injury-related diseases (4).

A Chinese study was conducted to study the effects of Astragalus Injection (AI) on humoral immunity (IgG, IgA, and IgM), cellular immunity (T-lymphocyte subsets), and soluble interleukin-2 in patients with CHF. There were 62 patients total with CHF whose heart function belonged to NYHA grade II-IV. The randomly assigned treatment group received 30ml (60g) of AI, whereas the control group received a 10mg nitroglycerine injection over a 20-day therapeutic course. There was significant heart function improvement noted in the treatment group vs. the control group. CD4 and CD4/CD8 levels increased while sIL-2R, IgG, and IgA levels were lowered significantly. From the results, it was concluded that AI has the potential to support heart-related immune function in patients with CHF (13).

Astragalus Possibly has Neuro-Protective Properties:

A Chinese study was conducted to observe the potential neurologically protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats. Following receiving right middle cerebral artery occlusion for 120 minutes, AST at 40mg/kg was administered to the male rats. Upon decapacitation following 1, 3, 7, and 14 days upon administration of the AST, neurological deficit scores, infarct volume, and water content of the brain were measured along with superoxide dismutase, lactate dehydrogenase, and nitric oxide synthase assessed to determine the effectiveness of AST in mediating the neurological biomarkers indicative of neural inflammation and/or progressive injury. Upon assessing the results, data suggested that AST was able to significantly reduce the neurological deficit score, infarct volume/water content, increase SOD, and LDH levels. It was concluded that AST might have potentially protective effects on focal cerebral ischemia (5).

In another study, the neuroprotective effects of an astragalus extract were investigated on mice that were chronically treated with stress-level dexamethasone (5mg/kg). Based on previous and current studies, dexamethasone, a glucocorticoid, can induce learning and memory impairments and neuronal cell apoptosis if present in elevated over long periods of time. As a baseline, it was observed that mRNA levels of caspase-3 and cytochrome c in the hippocampus and the neural cortex were significantly elevated following dexamethasone administration. The treatment groups were administered either 20 or 40mg/kg of astragalus extract or ginsenoside (6.5 mg/kg). Upon comparison of the baseline values, it was noted that both treatment groups had a significant increase in learning and memory capacity along with the downregulation of mRNA levels of the biomarkers that were previously elevated in the hippocampus and the neural cortex. The conducted study further supports the deleterious effects of stress-level dexamethasone on learning and memory, as well as the potential qualities of astragalus on neuronal protection (6).

In one recent study, the effects of Astragalus membranaceus was assessed in its ability to mediate stress-induced anxiety as well as learning and memory impairments in rats. For 14 days, restraint stress was induced 2 hours per day alongside a dosage of A. membranaceus (400 mg/kg). The following immunohistochemistry markers were assessed for stress-reduction levels: cholineacetyl transferase and tyrosine hydroxylase. Based on the results, the rats administered A. membranaceus significantly showed reduced stress levels based on a noted decrease in learning and memory deficits. It was also noted that A. membranaceus increased immuno-reactivities. Upon review of the results, it was concluded that A. membranaceus has the potential to recover behavioral and neurochemical impairments induced by stress (7).

Another supportive study was conducted to explore the effects of Astragalus membranaceus extract against cerebral ischemia injury by analyzing metabolic energy biomarkers and apoptosis pathways. Following a bilateral common carotid artery occlusion for 20 minutes, followed by 1-hour reperfusion, ATP content, total adenine nucleotides, energy charge, and sodium-potassium ATPase activity were markedly decreased in brain tissue. Upon comparison with the subjects that received administration of the A. membranaceus extract, it was noted that there were significant increases in ADP and ATP levels, energy charge value, and Na-K ATPase activity. The A. membranaceus extract also notably increased neurocyte survival and decreased neuronal apoptosis rates along with down-regulation of the expression of p-JNK1/2, Cyt C, caspase-9, and caspase-3. A review of the results concluded that A. membranaceus has neuroprotective effects against nerve injury following cerebral ischemia-reperfusion (8).

Astragalus Might have Cardioprotective Properties:

Unlike in Europe or the United States, Astragalus is a very highly studied herb in China. Some of the noted articles in the reference section related to cardiovascular health potential will be provided only as resource examples as they are either not readily accessible through the standard Medline database or have not been translated into English from Chinese.

One study observed the clinical efficacy and side-side effects of an Astragalus Injection (AI) in treating patients with congestive heart failure (CHF). Of the total 83 patients, 42 patients received 40 ml of AI, and the reminder 41 patients were noted as a control group and were treated with a 15 mg nitro-lingual injection with a 5% glucose solution. The therapeutic dose was administered for two weeks with a post-follow-up for 1-6 months.  Upon completion of the study, it was noted that there were significant improvements with the left ventricular ejection fraction, fractional shortening of the left ventricular short axis, the ratio of maximum blood flow between the advanced and early atrial systole, stroke volume, cardiac output, and cardiac index. Additionally, it was assessed that follow-ups showed a decrease in cardiac event incidence in the AI treatment group (11).

The second study investigated AI’s effect on plasma levels of apoptosis-related factors in aged patients with CHF.72 randomly assigned patients were divided into a treatment group (AI) and a control group (conventional treatment). The cardiac biomarkers measured to assess comparison were: plasma levels of soluble Fas, soluble Fas ligand, tumor necrosis factor-alpha, and interleukin-6. Grading was additionally assessed based on improved symptoms and left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricular ejection fraction. Following the 4-week treatment, significant symptom improvement was noted alongside decreased inflammatory biomarkers’ values in the treatment vs. control group. From the data, it was concluded that AI has the potential to lower plasma levels of apoptosis-related factors, along with the ability to improve cardiac function in aging patients with CHF (12).

A third Chinese study was conducted to explore the dose-dependent relationship of A. membranaceus granule administration on improving patients’ quality of life with chronic heart failure. The randomized study assessed 90 CHF patients who received either 7.5 g, 4.5 g, or 2.25 g of A. membranaceus two times daily and 4mg of a perindopril tablet once a day for 30 successive days. The measurements assessed prior and post-administration were the patient’s heart function grade, left ventricular ejection fraction, and walking distance in six minutes, along with a quality of life (QOL) assessment scored by the Minnesota Questionnaire for QOL evaluation in the patients with CHF. Upon analysis of the results, it was noted that heart function grades were improved in each treatment group, with the most considerable improvement seen in the group that received the 7.5 g dosage. Additionally, left ventricular ejection fraction levels and walking distances were significantly increased, respectively, correlated to the dosage administered. In relation to the QOL assessment tool, the high dose group, 7.5 g, was noted most effective with the highest QOL scores. From this study, there was sufficient data to conclude that A. membranaceus improved heart contraction while also showing a positive trend in a dose-dependent manner related to improving the QOL of patients with CHF (9).

Astragalus Potentially Support Healthy Kidney Function:

In one clinical study, a 77-year-old woman with nephrotic syndrome secondary to idiopathic membranous neuropathy was treated with a series of pharmaceuticals without response. 2 years later, following unremitting nephrosis, the patient began therapy with A. membranaceus. Following the herb’s administration at 15g/day, the patient’s proteinuria was markedly decreased. The patient’s nephrotic syndrome recurred following temporary cessation of A. membranaceus therapy. Upon re-introduction of the herb, complete remission of nephrosis was observed. Based on the patient’s results, it was concluded that A. membranaceus might have beneficial effects in patients with idiopathic membranous neuropathy (10).

SAFETY

Aside from select Chinese research under the reference of Traditional Chinese Medicine, there is limited research on astragalus and even less with human studies. With this in mind, based on the current research available on both human and animal subjects, astragalus is considered safe when taken orally or intravenously. Research conducted on rats safely administered a dose of 100 g/kg of Astragalus membranaceus without any noted side-effects (15).

Dosages will vary based on the condition being supported and one’s tolerance for the herb.  Safe dosages noted in research have supported 30 g/day for three months to 40g/day for two months orally or 80g/day for one month intravenously (14). Similar to other compounds, herbs, or nutraceuticals with limited research, it is advised to seek a consultation with your healthcare provider, especially if you are currently with any concern or condition(s) that may require a professional to follow your care before and during supplementation with astragalus.

Side-Effects:

Although very uncommon, those taking astragalus or a compound supplement with astragalus orally may experience rash, itchy skin, nasal symptoms, or stomach discomfort. Those on intravenous administration of astragalus may experience dizziness or an irregular heartbeat (14).

Those individuals with potentially undiagnosed or diagnosed auto-immune diseases such as multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis may experience a more active immune system when supplementing with astragalus. This combination could potentially worsen the symptoms of one’s auto-immune condition. It is recommended to avoid taking astragalus if one has an auto-immune condition or suspects he or she may have one (14).

Interactions:

Due to the limited research of astragalus and any of its derivatives, it is not recommended to consume the herb without first consulting your healthcare provider, especially if you are with any of these conditions and/or taking any prescriptions or supplements for the following (16):

• Antiviral Medications: Potential increase in efficacy of antiviral medications such as acyclovir or interferon
• Immunosuppressant Medications: Potential counteraction of immune-suppressing effects to cyclophosphamide (medication used to reduce the likelihood of organ transplant rejection) or corticosteroids
• Diabetic Medications: Potential to lower blood sugar, strengthening the effects of diabetic medications like insulin. Possible blood sugar misregulation can lead to episodes of hypoglycemia or diabetic coma if not properly regulated
• High Blood Pressure Medications: Potential to lower blood pressure, making the effects of the medications stronger
• Diuretics: Potential diuretic and may make the effects of the medications stronger
• Anti-Coagulant Medications: Potential to enhance the effects of blood-thinning medications, increasing the risk of bleeding or stroke

REFERENCES

1. Bensky D, Clavey S, Stoger E. Chinese Herbal Medicine: Materia Medica. Revised Edition. Eastland Press, 1993.
2. Zwickey H, Brush J, Iacullo CM, Connelly E, et al. The Effect of Echinacea Purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD25 Expression in Humans: A Pilot Study. Phytother Res. 2007;21(11): 1109-1112.
3. Cho WC, Leung KN. In Vitro and In Vivo Immunomodulating and Immuno-restorative Effects of Astragalus membranaceus. J Ethnopharmacol. 2007;113(1): 132-141.
4. Zhu YP, Shen T, Lin YJ, et al. Astragalus Polysaccharides Suppress ICAM-1 and VCAM-1 Expression in TNF-I-a-Treated Human Vascular Endothelial Cells by Blocking NF-kB Activation. Acta Pharmacological Sinica. 2013; 34:1036-1042.
5. Yanyan Y, Wei-Ping L, Hui-Ling G, Feng-Fang Z, Wei-Zu L, Guo-Cui W. Protective Effect of Astragaloside on Focal Cerebral Ischemia/Reperfusion Injury in Rats. American Journal of Chinese Medicine. 2010;38(3): 517-527. DOI: 10.1142/S0192415X10008020.
6. Wei-Zu L, Wei-Ping L, Wen Z, Yin-Yan Y, et al. Protective Effect of Extract of Astragalus on Learning and Memory Impairments and Neurons Apoptosis Induced by Glucocorticoids in 12-Month Male Mice. Anatomical Record. 2011;294(6): 1003-1014.
7. Park JH, et al. The Effects of Astragalus Membranaceus on Repeated Restraint Stress-Induced Biochemical and Behavioral Responses. Korean Journal of Physiol Pharmacol. 2009;13(4): 315-319.
8. Huang XP, Tan H, Chen BY, Deng CQ. Astragalus Extract Alleviates Nerve Injury After Cerebral Ischemia by Improving Energy Metabolism and Inhibiting Apoptosis. Bio Parm. Bull. 2012;35(4): 449-454. DOI: 10.1248/bpb.35.449.
9. Yang QY, Lu S, Sun HR. Clinical Effect of Astragalus Granule of Different Dosages on Quality of Life in Patients with Chronic Heart Failure. Chinese Journal of Integrative Med. 2011;17(2):146-149.
10. Ahmed MS, Hou SH, Battaglia MC, Picken MM, Leehey DJ. Treatment of Idiopathic Membranous Neuropathy with the Herb Astragalus membranaceus. American Journal of Kidney Disease. 2007;50(6): 1028-1032.
11. Zhou ZL, Yu P, Lin D. Study on Effect of Astragalus Injection in Treating Congestive Heart Failure. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001;21(10):747-749.
12. Zhang JG, et al. Effect of Astragalus Injection on Plasma Levels of Apoptosis-Related Factors in Aged Patients with Chronic Heart Failure. Chinese Journal of Integrative Med. 2005;11(3):187-190. doi: 10.1007/BF02836502.
13. Liu ZG, Xiong ZM, Yu XY. Effect of Astragalus Injection on Immune Function in Patients with Congestive Heart Failure. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003;23(5): 351-353.
14. Astragalus. https://www.rxlist.com/astragalus/supplements.htm#safetyConcerns. Accessed 17 July 2019.
15. Astragalus membranaceus. Monograph. Altern Med Rev. 2003;8(1): 72-77.
16. Possible Interactions with: Astragalus. Beaufort Memorial. https://www.bmhsc.org/health-and-wellness/education-support/health-library/article?productld=107&pid=33&gid=000878. Accessed 17 July 2019.
17. Seki K, Chisaka M, Eriguchi M, Yanagie H, Hisa T, Osada I, Sairenji T, Otsuka K, Halberg F. An attempt to integrate Western and Chinese medicine: rationale for applying Chinese medicine as chronotherapy against cancer. Biomed Pharmacother. 2005; 59: S132–S140.

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