Milk Vetch, Huang Qi (Astragalus membranaceous)

Indications

Used to support immune system functions, indicated in those with frequent infections and cancer, autoimmune disease, and allergic hyperreactivity.

Mechanism of Action

More than 100 “active” compounds, including flavonoids, saponins, polysaccharides, and amino acids have been identified in Astragalus thus far.¹ Among the most studied are the immune polysaccharides, including β-glucan and astragalin.

“Immune polysaccharides” are types of high-molecular-weight polysaccharides occurring in plants and are often credited with immune modulating action. Many immune polysaccharides, including those in Astragalus, are not easily absorbed and may trigger an immune response from direct effects on the intestinal mucosa and microbiota. Investigations with chicks show Astragalus to significantly increase beneficial lactobacilli and Bacillus cereus numbers, while decreasing Escherichia coli numbers and lymphocyte responsiveness.² Astragalus polysaccharides are also shown to promote proliferation and function of intestinal intraepithelial T cells, a group of specialized T cells most common in the gastrointestinal mucosa. Of various natural immunomodulators tested, β-glucan is consistently shown to be one of the most active in promoting both cellular and humoral immune responses.³

Numerous molecular, cell culture, animal, and in vitro research has shown Astragalus to have a wide array of immune-modulating actions involving T cells, T-cell receptors, cytokine production, and simultaneous up- and down-regulation of immune mediators. β-Glucan at 500 mg/kg is shown to decrease the release of inflammatory cytokines and corticosteroids and improve lymphocyte proliferative response via enhanced interleukin (IL)-2 bioactivity in piglets.⁴ It enhances both humoral and cellular immune responses via activating the TLR4 signaling pathway and inhibits the expression of transforming growth factor-β and frequency of Treg cells.⁵

Antiviral and Vaccine Adjuvant Effects: Astragalus is becoming established in veterinary medicine as a tool for boosting efficacy of poultry inoculations and possibly other livestock. Astragalus is noted to enhance the production of specific antibodies after hepatitis B virus,^5,6 vibrio,⁷ and respiratory viral vaccines in animal studies.⁸ Enhanced immune response is credited to effect T-cell ratios, cytokine responses such as interleukin and interferon production, and up-regulation of immune-enhancing genes.

Effects on Toll-Like Receptors: Toll-like receptor are involved with recognizing the presence of viruses and promoting immune responses in the body. Astragalus polysaccharides bind directly to Toll-like receptors on T-lymphocyte and macrophage surfaces⁹ and also increase the expression of Toll-like receptor⁵–enhancing immune responses including tumor necrosis factor-α, interleukin-6, and nuclear factor-κ B regulation. Up-regulation of Toll-like receptors contributes to the immune-modulating ability of Astragalus and is one of many mechanisms contributing to shifting the balance of T helper (Th)1 to Th2 cells and their release of cytokines. Activity at Toll-like receptors is credited with deterring herpes simplex invasion and cytokine response,¹⁰ reducing bacterial sepsis,¹¹ and promoting a shift from Th2- to Th1-dominated immune responsiveness.^12,13

Some bacteria, such as Escherichia coli, bind Toll-like receptor 4 on uroepithelium, and Astragalus polysaccharides have been shown to bind to this same location and trigger host immune response,¹⁴ promoting the secretion of interleukins-6 and -8 and deterring adhesion and biofilm establishment in the bladder.¹⁵

Anti-Fibrotic and Tissue Protective Effects: Activated hepatic stellate cells are the main contributors to excessive collagen deposition in liver fibrosis. Astragalus polysaccharide may induce apoptosis in overactive hepatic stellate cells, inhibiting cell proliferation via effects on gene expression,¹⁶ and Astragalus combinations have been shown to reduce fibrotic processes as evidenced by reduction in elevated hyaluronic acid, collagen, and procollagen levels in patients with fibrotic livers because of chronic hepatitis B.¹⁷ Astragalus may also help protect pancreatic beta cells from apoptosis and destruction via Th1/Th2 ratio shifts¹⁸ and the heart from tissue damage in animal models of acute myocarditis.¹⁹

Effects on Telomeres—Possible Longevity Mechanism: Telomeres are components of chromosomes that shorten each time a cell divides, until so little of the telomere is left that cell division is no longer possible, growth is arrested, and the cells are considered senescent, and incapable of further regeneration. Depletion of telomeres is directly related to longevity and involved with what determines a typical lifespan in various species. Telomerase enzymes are involved in protecting the average lifespan of the telomeres, and research is emerging on agents that deplete telomeres and shorten an organism’s lifespan as well as agents that activate telomerase and improve longevity. T cells are involved with telomerase activation, and Astragalus may improve longevity by effects on T-cell–driven telomerase. Astragalus compounds were shown to increase telomerase as much as 1.3 to 3.3 times in one study investigating effects on human T cells.²⁰ Telomerase also plays a role in cancer susceptibility and proliferation when excessive, whereas inadequate production of this enzyme results in physiological dysfunction and disease and rapid aging. Astragalus is shown to increase telomerase, and in turn lifespan, without increasing cancer incidence.^21,22 In fact, Astragalus has shown many anticancer effects.

Several of the immune polysaccharides in Astragalus are shown to activate telomerase, including astragaloside IV and cycloastragenol. These compounds promote CD8 T cell proliferation via up-regulation of phosphorylation of protein kinase–associated signaling pathways in numerous cell types including lung, brain, mammary, endothelial, fibroblast, and hematopoietic cells.²³ Astragalus may also improve T-cell responses in human immunodeficiency virus–infected patients by the same mechanism.²³

Muscle Supportive Effects: Muscle wasting is a consequence of low testosterone, cancer cachexia, and adrenal insufficiency, involving atrophy of myofibers and satellite cell apoptosis. Astragalus restores phosphorylation in muscle myotubes and myoblasts and protects muscle cell mitochondria.²⁴

Evidence-Based Research

Astragalus membranaceus has demonstrated many valuable bioactivities including immunomodulation^25,26; antioxidant, antitumor, and antiviral activities; and anti-inflammation. The immune-modulating properties are among the most studied aspects of Astragalus and include antitumor, antiviral, antiallergy, and antidiabetic activities.²⁷ The polysaccharide triterpene and flavonoid fractions are all credited with immune-regulating actions²⁸ and have been shown to decrease autoimmune destruction of the pancreatic beta cells²⁸ and reduce inflammation in animal models of autoimmune nephritis.²⁹

Poor adrenal function may be associated with poor immunity and frequent infections, and Astragalus has strong history of traditional use for infections, especially viral infections. A meta-analysis was performed of randomized controlled trials (RCTs) investigating the effects of A. membranaceus injection in tandem with conventional treatment, compared with conventional treatment alone in patients with viral myocarditis. Investigators reported Astragalus to significantly improve recovery based on electrocardiography findings and cardiac enzyme levels compared with conventional treatment alone, but noted that the methodological quality of the included trials was generally low.³⁰

Animal studies suggest Astragalus to improve stress tolerance³¹ and protect and improve mitochondrial function of individual muscle cells.²⁴ Animal studies have shown Astragalus improves stamina by improving exercise tolerance associated with increased hepatic and muscle glycogen content, compared with control.³²

Astragalus polysaccharide may attenuate chemotherapy side effects from platinum-based drugs (vinorelbine and cisplatin) in patients with advanced non-small-cell lung cancer. One RCT human trial dosed advanced non-small-cell lung cancer patients with either the pharmaceutical drug combo or the drug combo along with Astragalus. Although the survival time was not statistically different between the groups, quality-of-life parameters were better in the Astragalus group as evident after 3 months, with improved basic physical functioning, fatigue, appetite, digestive function, and pain.³³

A tissue culture study involving hepatocellular carcinoma patients investigated the effects of Astragalus on fresh tissue collected after radical hepatectomy surgeries. The samples were evaluated for the presence, migration, and proliferation of T regulatory cells and response to Astragalus. The researchers reported Astragalus to inhibit the growth and proliferation of cancer cells via normalizing cytokine imbalances and having an effect on mRNA and restoring the microenvironment in liver tissue, effects that might enhance the action of other therapies and increase the survival rate in liver cancer.³⁴

Poultry farmers are noting Astragalus to improve immunity and reduce various avian viruses to which chickens are prone and to improve outcomes when given in tandem with flu vaccines, improving antibody responses in the serum, and T-lymphocyte activity.^{35,36,37,38,39} Similar results are being reported in improving foot and mouth vaccine efficacy in pigs.⁴⁰

Safety in Pregnancy and Breastfeeding

Although there is no definitive or authoritative consensus, moderate use of Astragalus during pregnancy is most likely safe.

One rat study investigated the effects of astragaloside IV on fertility and early embryonic and perinatal toxicity. Astragaloside IV had no maternal toxicity, but it did show an inhibitory effect on female fertility. There was no evidence of early embryonic developmental toxicity but a dose of 1.0 mg/kg/day resulted in a significant delay in time for fur development and eye opening, compared with a control group, but it did not affect the memory and learning or other long-term consequences in the offspring.⁴¹

One study investigated the effects of Astragalus root on amnion cell cultures and reported significant improvements on inflammatory markers associated with initiating preterm labor, and the researchers proposed that Astragalus could be useful in protecting against preterm labor.⁴²

General Safety

Astragalus is considered safe enough to eat in food-like quantities, and animal studies have reported Astragalus to be well tolerated without deleterious effects.³² One study dosed female rats with
5 g/kg/day of the crude polysaccharide fraction and reported no genotoxic or mutagenic effects.⁴³ One RCT using Astragalus injections reported no adverse side effects.³⁰

Astragalus was traditionally used in teas or powders, often in combination with other herbs to help create prescriptions for specific purposes. Doses of 20, 50, 80, and even 100 g/day of crude Astragalus roots have been taken daily for weeks to months without reports of side effects.

Animal studies have dosed between 100 to 500 mg/kg.

Dosage

This herb is generally considered safe at dosages of several grams of raw herb per day or extracts of 1000–1500 mg/day.

Astragalus has been prepared in medicines intended for IV use for cancer where it is injected daily for several weeks. Parenteral preparations are increasingly being used as an adjuvant to chemotherapy in IV drips, daily for the 3-month courses of chemotherapy.

Traditional Uses

Astragalus membranaceus is one of the most widely used Chinese herbal medicines, used traditionally for “kidney yang deficiency” that has symptoms similar to the western concept of adrenal insufficiency or the clinical signs of cortisone cessation.⁴⁴ Astragalus is also traditionally considered to be a “Qi-tonic,” meaning it was held in high regard for improving energy, vitality, and longevity. These properties have also given Astragalus a long history of use for muscle wasting and immune modulation and as an all-purpose tonic. These Qi (or Chi)–tonifying properties of Astragalus could also be referred to as an “adaptogenic” action, a term coined by Russian research on Siberian ginseng, because of its many mechanisms that assist the body in resisting stress and improving immunity, energy, and adrenal function without being stimulating.

The immune-modulating properties of Astragalus have traditionally included both improving poor immune function in those with frequent infections and cancer as well as those with autoimmune disease and allergic hyperreactivity. Additional traditional uses for Astragalus include hepatoprotective, antidiabetic, respiratory anti-inflammatory, and antihypertensive uses; renal inflammation; and common viral and other infections.