astragalus

What is Astragalus

Astragalus (Astragali radix, Huang qi) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. (Family Leguminosae) root that contains numerous saponins and isoflavones 1). The genus Astragalus, commonly known as milk vetches, is comprised of more than 2,000 to 3000 species  and more than 250 taxonomic sections distributed worldwide 2). The Chinese Astragalus membranaceus and the related Astragalus mongholicus are thought to be varieties of the same species 3). Both are perennial herbs native to the northern provinces of China and are cultivated in China, Korea, and Japan. The dried root is used medicinally. Astragalus roots are sold as 15 to 20 cm long pieces that have a tough, fibrous skin with a lighter interior. It is sold as shredded roots, and in powder, tincture, and encapsulated form. Some products are produced by frying the roots with honey, although the untreated root itself also has a sweet, licorice-like taste.

Astragalus has been used as a dietary supplement for many conditions, including for diarrhea, fatigue, anorexia, upper respiratory infections, heart disease, hepatitis, fibromyalgia, and as an adjunctive therapy for cancer. Astragalus (Huang qi) has been used for centuries in Traditional Chinese Medicine in combination with other herbs, such as ginseng, dong quai, and licorice. A main traditional Chinese Medicine treatment principle is to strengthen the Zheng Qi (a concept of the body’s ability to self-regulate, pathogen resistance and self-recovery) and eliminate Evil Qi (pathogens) 4). This emphasises the importance of immune system functioning of patients and assumes that strengthening patients’ immune systems might prevent and control infections. Certain herbs have been found to affect the distribution and expression of cytokines and their receptors in the immune system 5). Astragalus (Huang qi), a herb widely used to strengthen Qi, is widely available in supermarkets in China. For many centuries, Astragalus, alone or in combination with other herbs, has been used by Traditional Chinese Medicine practitioners in the form of a water extract to prevent respiratory infections and to correct a condition called ‘Qi deficiency’, which typically includes symptoms such as: feelings of weakness, fatigue, apathy, poor appetite and vulnerability to respiratory infections 6). According to traditional Chinese medicine theory, Astragalus reinforces the body’s vital Qi, facilitates urination, promotes purulent discharge, and enhances soft tissue repair and growth 7). The diverse therapeutic functions of Astragalus mean that it is widely used by traditional Chinese medicine practitioners to treat a range variety of conditions including cardiovascular, cerebrovascular, kidney and digestive diseases 8). In daily clinical traditional Chinese Medicine practice, there are different routes of administration, such as injection, self-made oral water extraction, oral liquid and oral granules. The dosage or equivalent of raw Astragalus varies from 10 g/day to 20 g/day and is adjusted according to age. In China, astragalus alone or in combination with other herbs, is used by traditional Chinese medicine practitioners in the form of a water extract, to reduce the risk of acute respiratory tract infections; it is believed to stimulate the immune system. However, there are no high-quality studies in people of astragalus for any health conditions. Astragalus is also purported as a galactagogue (promotes or increases the flow of a mother’s milk); however, no scientifically valid clinical trials support this use. Galactogogues should never replace evaluation and counseling on modifiable factors that affect milk production. 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 infants. Astragalus is generally well tolerated, with mild gastrointestinal irritation and allergic reactions reported.

The flavonoids, cyclolanostane-type saponins and polysaccharides are the main bioactive compounds in Astragalus 9). Astragaloside IV, one of the cyclolanostane-type saponins, is used as a marker compound for quality control in the manufacture of Astragalus and its preparations 10).

Recent findings on astragalus membranaceus

  • Patients with nephrotic syndrome (health problems related to kidney damage) are susceptible to infections. A 2012 research review found that taking astragalus granules may be associated with a lower risk of infections in children with nephrotic syndrome. However, the review concluded that the studies were poor quality.
  • People with diabetic nephropathy (a type of kidney disease) who received an intravenous drip of astragalus over a period of 2 to 6 weeks did better on some measures of kidney function, compared to people who didn’t get astragalus, according to a 2011 analysis of 25 studies 11). However, most of the trials involved were poor quality.
  • There’s weak evidence that astragalus may help heart function in some patients with viral myocarditis (an infection of the heart), a 2013 research review showed.
  • Because of limitations in the studies, a 2013 research review 12) on the effects of astragalus on fatty liver disease, which causes fat to build up in liver cells, couldn’t determine whether astragalus helps.
  • A 2016 Cochrane Systematic review found insufficient evidence to enable assessment of the effectiveness and safety of oral Astragalus as a sole intervention to prevent frequent acute respiratory tract infections in children aged up to 14 years 13).
  • An astragalus-based herbal formula didn’t extend the life of patients with advanced lung cancer, a small 2009 trial reported.
  • Though a lot of results of pharmacological studies were carried out using crude extract of Astragalus species, the relationship between chemical constituents and activity is still unclear. Additionally, data on pharmacokinetics and bioavailability, especially related to the target tissue, need to be further supplemented.

Astragalus safety

Astragalus is considered safe for many adults. The most commonly reported side effects are diarrhea and other mild gastrointestinal effects. However, it may affect blood sugar levels and blood pressure and be risky for people with certain health problems, such as blood disorders, diabetes, or hypertension.
Astragalus may interact with medications that suppress the immune system, such as drugs taken by organ transplant recipients and some cancer patients.
Some astragalus species, usually not found in dietary supplements, can be toxic. Several species that grow in the United States contain the neurotoxin swainsonine and have caused “locoweed” poisoning in animals. Other species contain potentially toxic levels of selenium.

Figure 1. Astragalus membranaceus

Astragalus chemistry

A polymerase chain reaction method for measuring astragalus content in a polyherbal preparation has been published. Markers for each component were developed using decamer oligonucleotide primers 14). Hairy root cultures of astragalus have been established and produced cycloartane saponins 15). Saponin is the major chemical constituent type in the Astragalus genus. Cycloartane- and oleanane-type saponins from it showed interesting biological properties. The plants of Astragalus genus have been proved to be the richest source of cycloartane-type saponins, possessing cardiotonic, hypocholesteremic, anti-depressive and antiblastic actions as well as immunomodulatory activity 16). This promising spectrum of pharmacological effects led researchers to further search for structurally interesting cycloartane glycosides from the genus. Until now, more than 140 kinds of cycloartane-type saponins have been identified (Table 1). The main substituted sugar groups in them are β-d-glucopyranosyl (Glc), β-d-xylopyranosyl (Xyl), α-l-rhamnopyranosyl (Rha), or α-l-arabinopyranosyl (Ara). Additionally, β-d-glucuronopyranosyl (GlcA), β-d-fucopyranosyl (Fuc), β-d-apiofuranosyl (Api) and acetyl (Ac) groups were also found in cycloartane glycosides obtained from the Astragalus genus.

Astragalus root contains a series of cycloartane triterpene glycosides denoted astragalosides Ι to VΙΙ, that are based on the genin cycloastragenol and contain 1 to 3 sugars attached at the 3-, 6-, and 25-positions 17). In the predominant astragalosides Ι to ΙΙΙ, the 3-glucose is acetylated. Several saponins based on the oleanene skeleton also have been reported. 10 The aboveground parts of astragalus contain similar but distinct saponins in the cycloartane series 18) and many other species of astragalus contain cycloartane saponins 19).

Table 1. Cycloartane-type triterpenoids from the Astragalus genus

Compound’s NameSpecies ResourceParts UsedReference
13-O-[β-d-Xylopyranosyl(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucuronopyranosyl-3β,6α,16β,24(S),25-pentahydroxyxyxloartaneA. erinaceuswhole plant
2Hareftoside AA. erinaceuswhole plant
A. hareftaewhole plant
3Hareftoside BA. hareftaewhole plant
4Cycloquivinoside AA. chivensisaerial parts
5Astramembranosides BA. membranaceusroots
63-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-α-(4′-O-acetoxy)-l-arabinopyranosyl-16-O-acetoxy-3β,6α,16β,24S,25-pentahydroxycycloartaneA. wiedemannianuswhole plant
73-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-α-l-arabinopyranosyl-16-O-acetoxy-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. wiedemannianuswhole plant
8CyclocanthogeninA. unifoliolatusepigeal parts
A. chivensisaerial parts
93-O-β-d-Xylopyraosyl-24(S)-cycloart-3β,6α,16β,24,25-pentaol-25-O-β-d-glucopyranosideA. ernestiiroots
A. amblolepisroots
10Cyclocanthoside EA. hareftaewhole plant
A. oleifoliuslower stem parts
A. caucasicusleave s
11Cyclochivinoside BA. chivensisaerial parts
12Cyclochivinoside CA. chivensisaerial parts
13Caspicuside IA. caspicusroots
14Oleifoliosides AA. oleifoliuslower stem parts
15Oleifoliosides BA. oleifoliuslower stem parts
163-O-[α-l-Rhamnopyranosyl(1→2)-α-l-arabinopyranosyl(1→2)-β-d-xylopyranosyl]-6-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. aureuswhole plant
173,6-di-O-β-d-Xylopyranosyl-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydr-oxycycloartaneA. aureuswhole plant
183-O-β-d-Xylopyranosyl-6,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. aureuswhole plant
196-O-β-d-Glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. aureuswhole plant
203-O-[α-l-Arabinopyranosyl(1→2)-O-3-acetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. icmadophiluswhole plant
213-O-[α-l-Rhamnopyranosyl(1→2)-O-α-l-arabinopyranosyl(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. icmadophiluswhole plant
223-O-[α-l-Arabinopyranosyl(1→2)-O-3,4-diacetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. icmadophiluswhole plant
233-O-β-d-Xylopyranosyl-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. ernestiiroots
A. amblolepisroots
243-O-β-d-Xylopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartaneA. amblolepisroots
253-O-[β-d-Glucuronopyranosyl(1→2)-β-d-xylopyranosyl]-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy-cycloartaneA. amblolepisroots
263-O-β-d-Xylopyranosyl-24,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydr-oxy-cycloartaneA. amblolepisroots
276-O-α-l-Rhamnopyranosyl-16,24-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy cycloartaneA. amblolepisroots
286-O-α-l-Rhamnopyranosyl-16,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy cycloartaneA. amblolepisroots
29Cicerosides AA. ciceraerial parts
30Cicerosides BA. ciceraerial parts
31CycloascidosideA. ernestiiroots
A. amblolepisroots
A. mucidusaerial parts
32Eremophiloside AA. eremophilusaerial parts
33Eremophiloside BA. eremophilusaerial parts
34Cycloascidoside AA. mucidusaerial parts
35Cyclounifoliside CA. unifoliolatusepigeal parts
A. chivensisaerial parts
363-O-[α-l-Arabinopyranosyl(1→2)-β-d-glucopyranosyl]-24-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartaneA. stereocalyxroots
373-O-[α-l-Arabinopyranosyl(1→2)-β-d-glucopyranosyl]-16-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartaneA. stereocalyxroots
383-O-{α-l-Rhamnopyranosyl(1→4)-[α-l-arabinopyranosyl(1→2)]-β-d-glucopyranosyl}-3β,6α,16β,24(R),25-pentahydroxycycloartaneA. stereocalyxroots
393-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-16-O-β-d-glucopyranosyl-3β,6α,16β,20(S),24(R),25-hexahydroxycycloartaneA. stereocalyxroots
A. halicacabuswhole plant
A. campylosema Boiss. subsp. campylosemaroots
403-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-3β,6α,16β,20(S),24(R),25-hexahydroxycycloartaneA. stereocalyxroots
413-O-[α-l-Arabinopyranosyl(1→2)-β-d-glucopyranosyl]-3β,6α,16β,20(S),24(R),25-hexahdroxycycloartaneA. stereocalyxroots
423-O-β-d-Xylopyranosyl-3β,6α,16β,20(S),24(R),25-hexahydroxycycloartaneA. schottianusroots
43Cyclomacrogenin BA. macropusroots
44Cyclomacroside EA. macropusroots
45Cyclomacroside BA. macropusroots
46Cyclomacroside DA. macropusroots
47Mongholicoside AA. membranace (Fisch.) Bge. var. mongholicus (Bge.)aerial parts
48Mongholicoside BA. membranace (Fisch.) Bge. var. mongholicus (Bge.)aerial parts
49Askendoside KA. taschkendicusroots
50Askendoside HA. taschkendicusroots
51Cycloorbicoside DA. orbiculatusaerial parts
52Cycloorbigenin CA. taschkendicusroots
A. orbiculatusaerial parts
53Eremophiloside CA. eremophilusaerial parts
54Eremophiloside DA. eremophilusaerial parts
55Bicusposide FA. bicuspiswhole plant
56Bicusposide EA. bicuspiswhole plant
57Kahiricoside IIA. kahiricusaerial parts
58Kahiricoside IIIA. kahiricusaerial parts
59Kahiricoside IVA. kahiricusaerial parts
60Kahiricoside VA. kahiricusaerial parts
61Secomacrogenin BA. macropusroots
62OrbigeninA. orbiculatusaerial parts
63OrbicosideA. orbiculatusaerial parts
6416-O-β-d-Glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartaneA. hareftaewhole plant
65Astramembranosides AA. membranaceusroots
66Cyclosiversioside FA. oldenburgiiaerial parts
67Astraverrucin IVA. oldenburgiiaerial parts
68Astragaloside VIIA. oldenburgiiaerial parts
A. dissectusroots and stems
A. membranace (Fisch.) Bge. var. mongholicus (Bge.) hisaoroots
693-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl]-16-O-hydroxyacetoxy-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartaneA. angustifoliuswhole plant
70CyclolehmanosideCA. lehmannianusaerial parts
71Armatoside IIA. armatusroots
72Acetylastragaloside IA. baibutensisroots
73Astragaloside IIIA. illyricusroots
A. membracaceusroots
74Cyclounifolioside BA. illyricusroots
75Astraverrucin IA. illyricusroots
76Trigonoside IIA. armatusroots
A. halicacabuswhole plant
77Trojanoside HA. stereocalyxroots
A. armatusroots
78Armatoside IA. armatusroots
79Cyclosieversioside AA. sieversianusroots
80Cyclosieversioside GA. sieversianusroots
81Cyclosieversioside HA. sieversianusroots
823-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl]-25-O-β-d-glucopyranosyl-20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartaneA. wiedemannianuswhole plant
83CyclosiversigeninA. orbiculatusaerial parts
84Brachyoside BA. wiedemannianuswhole plant
85Astragaloside IIA. hareftae
A. wiedemannianus
whole plant
whole plant
86Astrasieversianin XA. wiedemannianuswhole plant
87Astrasieversianin IXA. sieversianusroots
88Caspicuside IIA. caspicusroots
89BaibutosideA. baibutensisroots
90Astragalosides IA. baibutensisroots
A. sieversianusroots
91Astraverrucin VIIA. verrucosusaerial parts
92Cycloaraloside D (Peregrinoside II)A. verrucosusaerial parts
A. angustifoliuswhole plant
93Cycloaraloside C (Astrailienin A)A. verrucosusaerial parts
94(20R,24S)-3-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-20,24-epoxy-16-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxycycloartaneA. halicacabuswhole plant
953-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-25-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartaneA. campylosema Boiss. subsp. campylosemaroots
963-O-[α-l-Arabinopyranosyl(1→2)-O-3-acetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartaneA. icmadophiluswhole plant
9720(R),24(S)-Epoxycycloartane-3β,6α,16β,25-tetraol-3-β-O-d-(2-O-acetyl)-xylopyranosideA. bicuspiswhole plant
983-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl]-16-O-hydroxyacetoxy-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartaneA. angustifoliuswhole plant
993-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl]-3β,6α,25-trihydroxy-20(R),24(S)-epoxycycloartane-16-oneA. angustifoliuswhole plant
1003-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartaneA. campylosema Boiss. subsp. campylosemaroots
1013-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-16-O-hydroxyacetoxy-23-O-acetoxy-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartaneA. campylosema Boiss. subsp. campylosemaroots
102Cyclogaleginoside EA. galegiformisstems
103Cycloascualoside DA. galegiformisstems
104Cyclogaleginoside CA. galegiformisstems
105CyclogalegigeninA. galegiformisstems
A. caucasicusleaves
106Cycloascauloside AA. caucasicusleaves
107Cyclogaleginoside DA. galegiformisstems
10820(R),25-Epoxy-3-O-β-d-xylopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxycycloartaneA. schottianusroots
10920(R),25-Epoxy-3-O-[-β-d-glucopyranosyl(1→2)]-β-d-xylopyranosyl-24-O-β-d-glucopyranosyl-3-β,6α,16β,24α-tetrahydroxycycloartaneA. schottianusroots
110Hareftoside CA. hareftaewhole plant
111CylotrisectosideA. dissectusroots and stems
1123-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartaneA. aureuswhole plant
1136-O-β-d-Glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartaneA. aureuswhole plant
1146-O-β-d-Xylopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartaneA. aureuswhole plant
1153-O-[α-l-Arabinopyranosyl(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartaneA. icmadophiluswhole plant
1163-O-[α-l-Rhamnopyranosyl(1→2)-O-α-l-arabinopyranosyl(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartaneA. icmadophiluswhole plant
117Eremophiloside GA. eremophilusaerial parts
118Eremophiloside EA. eremophilusaerial parts
119Eremophiloside FA. eremophilusaerial parts
120Eremophiloside HA. eremophilusaerial parts
121Eremophiloside IA. eremophilusaerial parts
122Eremophiloside JA. eremophilusaerial parts
123Eremophiloside KA. eremophilusaerial parts
124Cyclomacroside AA. macropusroots
125Bicusposide DA. bicuspiswhole plant
1263-O-[α-l-Arabinopyranosyl(1→2)-β-d-xylopyranosyl]-3β,6α,23α,25-tetrahydroxy-20(R),24(R)-16β,24;20,24-diepoxycycloartaneA. campylosema Boiss. subsp. campylosemaroots
127Dihydrocycloorbigenin AA. orbiculatusaerial parts
128CycloorbigeninA. orbiculatusaerial parts
129Cycloorbigenin BA. orbiculatusaerial parts
130Cycloorbicoside AA. orbiculatusaerial parts
131Cycloorbicoside BA. orbiculatusaerial parts
132Cycloorbicoside CA. orbiculatusaerial parts
133Cycloorbicoside GA. orbiculatusaerial parts
134Tomentoside IA. tomentosusaerial parts
135Deacetyltomentoside IA. tomentosusaerial parts
136Tomentoside IIIA. tomentosusaerial parts
137Tomentoside IVA. tomentosusaerial parts
138Huangqiyenin EA. membranaceusleaves
139Huangqiyenin FA. membranaceusleaves
140Huangqiyegenin IIIA. membranaceusleaves
141Huangqiyegenin IVA. membranaceusleaves
142Trideacetylhuangqiyegenin IIIA. membranaceusleaves
[Source 20)]

Apart from the cycloartane triterpene glycosides, many oleanane-type saponins shown in Table 2 were also isolated and identified from the Astragalus genus. Structure characterizations of this kind of saponin indicated they were substituted with a β-hydroxymethyl, instead of methyl in the 23-position.

Table 2. Oleanane triterpenoids from the Astragalus genus

Compound’s NameSpecies ResourceParts UsedReference
1433-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-21-O-α-l-rhamnopyranosyl-3β,21β,22α,24-tetrahydroxyolean-12-eneA. tauricoluswhole plant
1443-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl(1→2)-β-d-glucuronopyranosyl]-21-O-α-l-rhamnopyranosyl-3β,21β,22α,24-tetrahydroxyolean-12-eneA. tauricoluswhole plant
1453-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl(1→2)-β-d-glucuronopyranosyl]-3β,21β,22α,24,29-pentahydroxyolean-12-eneA. tauricoluswhole plant
1463-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-22-O-α-l-rhamnopyranosyl-3β,22β,24-trihydroxyolean-12-eneA. tauricoluswhole plant
1473-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-3β,21β,22α,24,29-pentahydroxyolean-12-eneA. angustifoliuswhole plant
1483-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-3β,22β,24-trihydroxyolean-12-en-29-oic acidA. angustifoliuswhole plant
1493-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-22-O-α-l-arabinopyranosyl-3β,22β,24-trihydroxyolean-12-eneA. angustifoliuswhole plant
15029- O-β-d-Glucopyranosyl-3β,22β,24,29-tetrahydroxy-olean-12-eneA. angustifoliuswhole plant
151Soyasapogenol BA. caprinusroots
A. bicuspiswhole plant
1523-O-[β-d-Xylopyranosyl(1→2)-O-β-d-glucopyranosyl(1→2)-O-β-d-glucuronopyranosyl] soyasapogenol BA. hareftaewhole plant
1533-O-α-l-Rhamnopyranosyl(1→2)-β-d-glucuronopyranosyl]-22-O-β-d-apiofuranosyl soyasapogenol BA. caprinusroots
1543-O-[α-l-Rhamnopyranosyl(1→2)-β-d-xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24-trihydroxyolean-12-en-29-oic acidA. tauricoluswhole plant
1553-O-[α-l-Rhamnopyranosyl(1→2)-β-d-glucopyranosyl(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acidA. tauricoluswhole plant
1563-O-[β-d-Xylopyranosyl(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acidA. tauricoluswhole plant
1573-O-[α-l-Rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,29-tetrahydroxyolean-12-eneA. tauricoluswhole plant
1583-O-[α-l-Rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,24-dihydroxyolean-12-ene-22-oxo-29-oic acidA. tauricoluswhole plant
1593-O-[β-d-Glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acidA. tauricoluswhole plant
160Azukisaponin VA. cruciatusaerial parts and roots
A. hareftaewhole plant
161Astragaloside VIIIA. flavescensroots
A. cruciatusaerial parts and roots
A. hareftaewhole plant
A. wiedemannianuswhole plant
A. icmadophiluswhole plant
A. angustifoliuswhole plant
[Source 21)]

Just like many other herbs, Astragalus genus plants are also a rich source of flavonoids. The flavonoids in this genus include flavonols, flavone, flavonones and isoflavonoids, which have many kinds of bioactivities. In addition, some special flavonoids, such as sulfuretin, isoliquiritigenin and pendulone have been obtained.

A variety of immune polysaccharides have been reported from astragalus root. Yao et al 22), analyzed the monosaccharide compositions for the Radix Astragali polysaccharide by gas chromatography, and identified the monosaccharides in it as arabinose, fructose, glucose, and mannose.  Xu et al., isolated and purified two kinds of Astragalus polysaccharides (APS) (APS-I and APS-II) from the water extract of Radix Astragali. The research indicated that APS-I consisted of arabinose and glucose in the molar ratio of 1:3.45, with molecular weight 1,699,100 Da; meanwhile, APS-II consisted of rhamnose, arabinose and glucose in a molar ratio of 1:6.25:17.86 with molecular weight 1,197,600 Da 23).

Astragalan Ι is a neutral 36 kD heterosaccharide containing glucose, galactose, and arabinose, while astragalans ΙΙ and ΙΙΙ are 12 kD and 34 kD glucans, respectively 24). Three similar polysaccharides and an acidic polysaccharide, AG-2, were isolated 25). A complex 60 kD acidic polysaccharide, AMem-P, with a high hexuroic acid content from A. membranaceus 15 and a similar but distinct 76 kD acidic polysaccharide, AMon-S from A. mongholicus were reported 26). Polysaccharides known as astroglucans A-C from Astragalus membranaceus were patented 27).

Isoflavan glycosides based on mucronulatol and isomucronulatol have been found in the roots of Astragalus membranaceus 28). Several products appear to use these compounds for standardization despite the lack of reported biological activity. In addition, the free isoflavones afrormosin, calycosin, formononetin, and odoratin have been isolated from the roots 29).

A unique biphenyl was isolated from Astragalus membranaceus var. mongholicus as an antihepatotoxic agent 30).

Astragalus root benefits

Acute respiratory tract infections in children

A study has suggested that Astragalus confers some immune-stimulating effects, including promoting white blood cell production, accelerating peripheral blood mononuclear cells and cytokine proliferation 31). Hou 32) found that healthy people who received oral Astragalus (8 g per day) for two months experienced significant improvement in the interferon-inducing ability of blood cells compared with control group participants. Two months after therapy ceased, the interferon-inducing ability remained significantly higher in the Astragalus group. In another study, Astragalus extract was prescribed to healthy adults for 20 consecutive days and increases were observed in immune parameters such as immunoglobulin (Ig) M, IgE and cyclic adenosine monophosphate 33). Nie 34) demonstrated that Astragalus could decrease soluble interleukin-2 receptor and interleukin-8 levels, while increasing IgA, IgM and IgG levels in patients experiencing recurrent upper respiratory tract infections (URTIs). Based on these findings, Astragalus may have a biological basis for use in preventing acute respiratory tract infections in children. Astragalus is a herb, extensively used both in clinical practice and as a food supplement in daily life in China. Although it is widely used to prevent acute respiratory tract infection in children who experience frequent episodes, no definitive conclusions about its effectiveness have been determined. Safety is an important concern, especially in the context of medications for children. Allergic reactions to Astragalus injections have been reported, and the safety of oral Astragalus preparation remains unclear 35). However, a well conducted 2016 Cochrane Systematic review found insufficient evidence to enable assessment of the effectiveness and safety of oral Astragalus as a sole intervention to prevent frequent acute respiratory tract infections in children aged up to 14 years 36). The review authors did not identify any randomized clinical trials that investigated the effectiveness and safety of oral Astragalus compared with placebo to prevent frequent episodes of acute respiratory tract infections in children 37). There is no placebo-controlled randomized controlled trial evidence is available to help guide practice, family decisions about care, or healthcare policy in relation to oral Astragalus for preventing frequent acute respiratory tract infection episodes among children in community settings. Large, well-designed randomized controlled trials investigating the safety and efficacy of oral Astragalus to prevent frequent acute respiratory tract infections in children are needed.

Chronic kidney disease

Chronic kidney disease (CKD) is characterised by gradual deterioration of kidney function caused by an array of medical conditions such as diabetes, hypertensive nephrosclerosis, glomerulonephritis and renovascular disease 38). According to the Kidney Disease Outcomes Quality Initiative clinical guidelines, chronic kidney disease can be defined as either kidney damage (indicated by markers such as abnormalities in urine or blood tests, or on imaging), or decreased glomerular filtration rate (GFR < 60 mL/min/1.73 m²) with or without evidence of kidney damage, for three or more months, irrespective of the cause. Based on GFR levels, chronic kidney disease can be further classified according to disease stage 39):

  • Stage 1: kidney damage with normal or increased GFR (≥ 90 mL/min/1.73 m²)
  • Stage 2: kidney damage with mild decreased GFR (60 to 89 mL/min/1.73 m²)
  • Stage 3: moderately decreased GFR (30 to 59 mL/min/1.73 m²)
  • Stage 4: severely decreased GFR (15 to 29 mL/min/1.73 m²)
  • Stage 5: kidney failure with GFR < 15 mL/min/1.73 m² or a need for dialysis.

Decreased kidney function is closely associated with a range of complications including hypertension, anemia, malnutrition, bone disease, neuropathy, and reduced quality of life 40). Moreover, it is an independent risk factor for cardiovascular diseases 41).

Incidence of chronic kidney disease is widespread and imposes substantial burden on healthcare systems globally. The median prevalence of moderate-to-severe chronic kidney disease (GFR < 60 mL/min/1.73 m²) has been estimated at 7.2% in people aged 30 years and over, but escalates to 23.4% to 35.8% in people 64 years and over 42). Both numbers of people with end-stage kidney disease who need dialysis or kidney transplantation and treatment resource costs have continued to increase. Resource limitations mean that many people with end-stage kidney disease in both economically developed and developing regions do not have access to dialysis or kidney transplantation 43). Delaying progression to end-stage kidney disease therefore benefits both patients and healthcare systems.

Chronic kidney disease affects increasing numbers of people around the world, but as yet, effective strategies to control its progression have not been universally accepted. Astragalus is one of most widely used herbs for treating kidney disease.

Although a study 44) found some promising evidence suggesting that when given with conventional treatment, Astragalus may help to decrease the serum creatinine, reduce the amount of protein lost in urine and diminish the effects of some complications, such as anemia and malnutrition, evidence quality was low. The study authors 45) found that errors and omissions in study methods and reporting were likely to have flawed results among the studies they assessed, therefore definitive conclusions could not be made based on available evidence. Further studies designed to incorporate scientifically rigorous methodology are required before conclusions can confidently be reached about the effects of Astragalus for the treatment of people with chronic kidney disease. Possible adverse effects associated with Astragalus injection should be noted, although the study authors found no relevant reports from included studies.

Astragalus uses

In traditional Chinese medicine practice, Astragalus is used to tonify Qi. In traditional Chinese medicine theory, Qi is one of the material elements of life activities in the human body. According to Chinese medicine treatment principles, disease caused by Qi insufficiency should be treated with Qi tonifying medications, and prescriptions. In modern Chinese medicine, Astragalus is used either alone or in combination with other herbs in oral decoction, pill or capsule forms. Astragalus is also manufactured in injectable form for intravenous and intramuscular administration.

Different Astragalus species are used in traditional medicine, mostly Chinese, and the dried roots of Astragalus membranaceus (Fisch.) Bge and Astragalus membranaceus (Fisch.) var. mongholicus (Bge) Hsiao are included in the drug Huang qi (Radix Astragali), which is present in the pharmacopoeia of the People’s Republic of China 46).

Astragalus membranaceus, Astragalus mongholicus and Astragalus complanatus have been mainly used in folk medicine for their anti-inflammatory, immunostimulant, antioxidative, anti-cancer, antidiabetic, cardioprotective, hepatoprotective, and antiviral properties in recent years. The active constituents for the above-mentioned effects were proved to be polysaccharides, saponins, and flavonoids.

Astragalus membranaceus is used as a tonic and has many effects, such as enhancing defensive energy and inducing diuresis to treat edema 47). Astragalus membranaceus is widely used in East Asia as antiperspirants, diuretics, and tonics for a wide array of diseases such as empyrosis, nephritis, diabetes mellitus, hypertension, cirrhosis, leukaemia, and uterine cancer 48) and liver fibrosis 49). Moreover, recent pharmacological studies and clinical evidence centered on Astragalus membranaceus have reported a wide spectrum of biological activities for this plant 50), including at an intestinal level 51). Astragali radix, the dried root of Astragalus membranaceus, is a popular health-promoting herb, and its use as a crude drug is one of the oldest and most frequently used remedies in oriental medicine 52). Pharmacological studies have demonstrated that the water extract of Astragali radix possesses many biological functions 53). Also, Astragalus polysaccharides, which are major constituents of Astragali radix, possess many biological effects and pharmacological properties, including at intestinal levels 54). Despite this, there is little mechanistic knowledge regarding the molecular action(s) of Astragalus membranaceus root extract on intestinal epithelial cells 55) and especially during inflammatory conditions. Astragalus membranaceus root extract significantly reduced the inflammatory response and the pro-oxidant status in intestinal epithelial cells-6 cells. Astragalus polysaccharides may have the potential benefit of acting as intestinal epithelial wound healing modulators in vivo 56).

A number of clinical studies have shown that Astragalus can improve kidney function, reduce proteinuria, increase serum superoxide dismutase, decrease lipid peroxidation, decrease endothelin-1 and regulate cellular immunity in patients with moderate to severe chronic kidney disease 57). Pharmacological studies have also demonstrated that Astragalus may offer immunomodulatory 58), anti-inflammatory 59) and renoprotective effects 60). Astragalus may also ameliorate renal interstitial fibrosis 61), inhibit glomerular mesangial cell proliferation and interleukin-6 secretion 62). These mechanisms may account for improvements in kidney function and chronic kidney disease clinical symptoms that have been attributed to Astragalus.

Astragalus root may have use in the restoration of immune function after cancer chemotherapy and for the treatment of HIV infection. However, there are no clinical trials to support any of these uses.

Immunostimulant

The most common use of astragalus root in herbal medicine in the United States is as an immunostimulant to counteract the immune suppression associated with cancer chemotherapy. This use is based on several observations.

Animal/Clinical data

The cycloartane saponins are capable of stimulating the growth of isolated human lymphocytes 63). The polysaccharides astragalans Ι and ΙΙ were found to potentiate immunological responses in mice following intraperitoneal administration but not after oral administration 64). The glycans AMem-P and AMon-S increased phagocytic indices with intraperitoneal injection into mice 65).

Aqueous extract of astragalus root stimulated phagocytosis of mice macrophages and augmented proliferation of human monocytes in response to phytohemagglutinin, concanavalin A, and pokeweed mitogen 66). In cells from cancer patients, which were comparatively resistant to such stimulation, astragalus extract also stimulated mononuclear cells. Using a graft versus host model, astragalus extract restored the graft versus host reaction in vivo for healthy and immunosuppressed patients 67).

These in vitro and in vivo effects justify further human trials of the immunostimulant activity of astragalus root extracts in patients whose immune systems have been suppressed by cancer chemotherapeutic drug regimens.

HIV

Another use of astragalus root in the United States is in the treatment of HIV infection. It may help reduce opportunistic infections, but such use depends on a host-mediated response because the aqueous extract of astragalus has no direct effect on viral infectivity 68) and little effect on viral reverse transcriptase 69).

Animal data

Research reveals no animal data regarding the use of astragalus in HIV.

Clinical data

A pilot trial of a Chinese herbal formulation containing astragalus root was found to improve subjective measures and symptomatology; however, the number of subjects was too small to detect statistically meaningful effects 70).

A series of unverified reports from China claim that treatment with herbal mixtures including astragalus can induce seronegative conversion in a small fraction of HIV patients 71).

In view of revised opinions on the population dynamics of the HIV virus in infected humans, an attempt to stimulate T-cell proliferation may not be a realistic therapeutic objective because the turnover rate is rapid. Nevertheless, improvement in subjective symptoms in the above study 72) cannot be ignored, and a larger clinical trial might confirm these effects as important.

Other uses

Astragalus often is recommended for the prevention of the common cold; however, there are no published clinical trials that support this use.

The biphenyl compound 4,4′,5,5′,6,6′-hexahydroxy-2,2′-biphenyldicarboxylic acid 5,6:5′,6′-bis (methylene), 4,4′-dimethyl ether, dimethyl ester was isolated as the antihepatotoxic principle of astragalus root 73). The isoflavones afrormosin, calycosin, and odoratin had antioxidant activity similar to butyl hydroxytoluene or alpha-tocopherol in several experimental models of air oxidation of lipids 74).

Astragalus root saponins also has diuretic activity presumed to be caused by local irritation of the kidney epithelia. 29 Astragalus saponins showed anti-inflammatory and hypotensive effects in rats 75).

Anti-Inflammatory Activity

Astragalus extract, along with its polysaccharides, and saponins showed anti-inflammatory activity both in vitro and in vivo. Kim et al. 76), found that the extract of Astragalus membranaceus not only improved the atopic dermatitis skin lesions in 1-chloro-2,4-dinitrobenzene-induced mice as well as restoring nuclear factor-κB expression markedly, but also suppressed the expression of Th2 cytokines and significantly decreased the TNF-α level. They then figured out that A. membranaceus was effective for treating atopic dermatitis by regulating cytokines. Ryu et al. 77), verified that Astragali Radix had an anti-inflammatory effect mediated by the MKP-1-dependent inactivation of p38 and Erk1/2 and the inhibition of NFkappaB-mediated transcription. As the main composition of Astragalus, Astragalus polysaccharides can effectively ameliorate the palmitate-induced pro-inflammatory responses in RAW264.7 cells through AMPK activity 78). They also showed anti-inflammatory activity, along with structure protective properties for lipopolysaccharide-infected Caco2 cells 79). On the other hand, the anti-inflammatory activity of saponins was also studied. The results, of agroastragalosides I, II, isoastragaloside II, and astragaloside IV showed the ability to inhibit lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages 80). Meanwhile, astragaloside IV was shown to be a promising natural product with both healing and anti-scar effects for wound treatment 81), could be used as a novel anti-inflammatory agent, and attenuated diabetic nephropathy in rats by inhibiting NF-κB mediated inflammatory gene expression 82).

Immunoregulatory Activity

Qin et al. 83), studied the effect of Astragalus membranaceus extract on the advanced glycation end product-induced inflammatory response in α-1 macrophages. The results suggested that it could inhibit advanced glycation end product-induced inflammatory cytokine production to down-regulate macrophage-mediated inflammation via p38 mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathways. Du et al. 84), investigated the potential adjuvant effect of Astragalus polysaccharides on humoral and cellular immune responses to hepatitis B subunit vaccine. The result suggested that it was a potent adjuvant for the hepatitis B subunit vaccine and could enhance both humoral and cellular immune responses via activation of the Toll-like receptor 4 signaling pathway and inhibit the expression of transforming growth factor β. Nalbantsoy et al. 85), studied the in vivo effects of two Astragalus saponins on the immune response cytokines by using six to eight week old male Swiss albino mice. The results showed that astragaloside VII and macrophyllosaponin B showed powerful immunoregulatory effects without stimulation of inflammatory cytokines in mice, and had no significant effect on the inflammatory cellular targets in vitro. Huang et al. 86) found that astragaloside IV could rival the suppressing effect of high mobility group box 1 protein on immune function of regulatory T cells with dose-dependent in vitro.

Anti-Tumor Activity

Recently, many active screening results have indicated that Astragalus polysaccharides, saponins, and flavonoids have anti-tumor activities. Tian et al. 87), investigated the adjunct anticancer effect of Astragalus polysaccharides on H22 tumor-bearing mice, and found that it exerted a synergistic anti-tumor effect with adriamycin and to alleviate the decrease in the sizes of the spleen and thymus induced by adriamycin in H22 tumor-bearing mice. As a potential anti-tumor saponin, astragaloside IV could down-regulate Vav3.1 expression in a dose- and time-dependent manner 88). Meanwhile, astragaloside II could down regulate the expression of the P-glycoprotein and mdr1 gene, which suggested it was a potent multidrug resistance reversal agent and could be a potential adjunctive agent for hepatic cancer chemotherapy 89). On the other hand, the experimental data showed that the total flavonoids of Astragalus and calycosin could inhibit the proliferation of K562 cells 90).

Cardioprotection Activity

Ma et al. 91), studied the cardio protective effect of the extract of Radix Astragali on myocardial ischemia and its underlying mechanisms in ROS-mediated signaling cascade in vivo by using different rat models, and drew the conclusion that the cardio protection was due to a protection of tissue structure and a decrease in serum markers of the ischemic injury. The total flavonoids of A. mongholicus are the active components, which benefit cardiovascular disease attributed to the potent antioxidant activity in improving the atherosclerosis profile 92). Isoflavones, calycosin and formononetin from the Astragalus root, could promote dimethylarginine dimethylaminohydrolase-2 protein and mRNA expressions in Madin Darby Canine Kidney (MDCK) II cells, and up regulate the neuronal nitric oxide synthase levels 93). Astragaloside IV could prolong the action potential duration of guinea-pig ventricular myocytes, which might be explained by its inhibition of K+ currents 94).

Antidiabetic

The study of Liu et al. 95), indicated that Astragalus polysaccharide could regulate part of the insulin signaling in insulin-resistant skeletal muscle, and could be a potential insulin sensitizer for the treatment of type 2 diabetes. Zhou et al. 96), found Astragalus polysaccharide could up regulate the expression of galectin-1 in muscle of type I diabetes mellitus mice. Saponins and astragaloside IV could exert protective effects against the progression of peripheral neuropathy in streptozotocin-induced diabetes in rats 97). In addition, astragaloside V was found to inhibit the formation of N-(carboxymethyl)lysine and pentosidine during the incubation of bovine serum albumin with ribose, which suggested that it might be a potentially useful strategy for the prevention of clinical diabetic complication by inhibiting advanced glycation end products 98).

Anti-Oxidative Activity

The anti-oxidative activities of some flavonoids and saponins from Astragalus mongholicus have been studied. For example, formononetin, calycosin, calycosin-7-O-β-d-glucoside could scavenge 1,1-diphenyl-2-picrylhydrazyl free radicals in vitro. Formononetin and calycosin were found to inhibit xanthine/xanthine oxidase-induced cell injury significantly. Among them, calycosin exhibited the most potent antioxidant activity both in the cell-free system and in the cell system 99). The compound 7,2-dihydroxy-3′,4′-dimethoxyisoflavan-7-O-β-d-glucoside and calycosin-7-O-β-d-glucoside from A. membranaceus showed anti-lipid peroxidative activities 100). The saponin, astragaloside IV can inhibit hepatic stellate cells activation by inhibiting generation of oxidative stress and associated p38 MAPK activation 101).

Anti-Aging

According to the study of the anti-aging effect of astragalosides, Lei et al. 102), suggested that the mechanism might be related to the improvement of brain function and immunomodulatory effects. Gao et al. 103), concluded that Astragalus polysaccharides could lengthen the living time of mice, improve the activity of superoxide dismutase and decrease the malonaldehyde content in mice blood serum compared with the control group, which suggested that Astragalus polysaccharides have anti-aging effects.

Astragalus dosage

There is no recent clinical evidence to guide dosage of astragalus products; however, typical recommendations are 2 to 6 g daily of the powdered root.

Astragalus side effects

Research reveals little or no information regarding adverse reactions with the use of this product.

Dietary supplements do not require extensive pre-marketing approval from the U.S. Food and Drug Administration. Manufacturers are responsible to ensure the safety, but do not need to prove the safety and effectiveness of dietary supplements before they are marketed. Dietary supplements may contain multiple ingredients, and differences are often found between labeled and actual ingredients or their amounts. A manufacturer may contract with an independent organization to verify the quality of a product or its ingredients, but that does not certify the safety or effectiveness of a product. Because of the above issues, clinical testing results on one product may not be applicable to other products.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

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 infants. Astragalus is generally well tolerated, with mild gastrointestinal irritation and allergic reactions reported.

More detailed information about dietary supplements is available elsewhere on the LactMed site here (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm).

Toxicology

An astragalus hot water extract that had been boiled for 90 minutes was mutagenic in the Ames test in S. typhimurium TA98 when activated by S9 rat liver fractions. The activity was dose-dependent. In addition, the mutagenic activity was not removed by XAD-2 resin treatment. The same preparations given by intraperitoneal injection at 1 to 10 g/kg produced chromosomal aberrations in the bone marrow of mice, and increased the incidence of micronucleated cells in bone marrow. No attempt was made to isolate the mutagenic compounds responsible for these effects 104).

The pharmacology and toxicology of the genus Astragalus have been reviewed 105).

References   [ + ]

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