Astragalus propinquus Schischkin

Last updated: 15 Mar 2016

Scientific Name

Astragalus propinquus Schischkin 

Synonyms

Astragalus membranaceus (Fisch.) Bunge, Phaca membranacea Fisch., Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsia , Astragalus propinquus var. glabra Vydr. [1]

Vernacular Name

English Membranous milk vetch, Mongolian milk vetch [2]
China Huang qi, huangqi [2]

Geographical Distributions

Astragalus propinquus is native to the northern and eastern parts of China, as well as Mongolia and Korea. [3]

Botanical Description

A. propinquus falls under the family of Leguminosae and is a perennial plant, about 16 to 36 inches tall.

The stems are hairy with leaves made up of 12 to 18 pairs of leaflets. [3]

The root is the medicinal part of the plant, and is usually harvested from 4-year-old plants. [3]

Cultivation

No documentation.

Chemical Constituent

Methanol extract of A. propinquus dried roots has been reported to contain flavonoids (e.g. isoliquiritigenin, liquiritigenin, calycosin, calycosin 7-O-b-D-glucoside, formononetin, formononetin 7-O-b-D-glucoside, daidzein, daidzein 7-O-b-D-glucoside, methylnissolin, methylnissolin 3-O-b-D-glucoside, isomucronulatol, and isomucronulatol 7-O-b-D-glucoside). [4]

Ethanol (70%) extract of A. propinquus  stems has been reported to contain oleanane type saponins (e.g. astroolesaponins A, astroolesaponins B, astroolesaponins C1, astroolesaponins C2, astroolesaponins D, astroolesaponins E1, astroolesaponins E2, astroolesaponins F, azukisaponin V, azukisaponin V methyl ester, astragaloside VIII methyl ester, robinioside F, robinioside B, and cloversaponin III) [5]. Meanwhile the extract of the leaves has been reported to contain cycloartane triterpenes (e.g. huangqiyegenins V, huangqiyegenins VI, huangqiyenins K and huangqiyenins L) [6].

Aqueous ethanol (70 %) extract of A. propinquus  dried stem has been reported to contain cyclolanstane-type saponins (e.g. astrolanosaponins A1, A2, B, C, D, E, cycloastragenol-3-Ob-D-glucopyranoside, astraverrucinII, cycloaraloside E, huangqiyenin A, huangqiyenin B, and aleksandroside I) [7].

A. propinquus  roots has been reported to contain isoflavonoids (e.g. formononetin, ononin, calycosin, calycosin-7-O-β-3-D-glucopyranoside, (6aR, 11aR)-3-hydroxy-9,10-dimethoxypterocarpan, (6aR, 11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-β-D-glucopyranoside, (3R) -7,2'-dihydroxy-3', 4'-dimethoxyisoflavan, (3R) -7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan-7-O-β-D-glucopyranoside, 6"-O-acetyl-ononin, 6"-O-acetyl-(3R) -7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan-7-O-β-D-glucopyranoside, 6"-O-acetyl-(6aR, 11aR)-3-hydroxy-9, 10-dimethoxypterocarpan-3-O-β-D-glucopyranoside, pratensein, sissotrin and 5,7,4'-trihydroxy-3'-methoxyisoflavone). [8]

Plant Part Used

Root [9][10]

Traditional Use

A. propinquus has been used in traditional Chinese medicine by decoction of root for the treatment of fatigue with poor appetite and diarrhoea, prolapse of the uterus and rectum, abnormal uterine bleeding, and spontaneous sweating [9]. A. propinquus is also taken as the powdered dried root or decoction and used for postpartum fever and recovery from severe loss of blood. [10][11][12][13]

In Oriental countries, it is widely used to prevent and treat common colds and upper respiratory tract infections. In western countries, the most common use of A. propinquus is as an immune support supplement to the daily diet and as an immunostimulant to counteract the immune suppression associated with cancer chemotherapy and radiotherapy. In TCM, A. propinquus is often combined with other herbs such as angelica and ginseng, in various complex prescription formulas. Such herbal formulas have been used for centuries in Asia to treat diabetes, kidney infections, strokes and many other diseases [14].

Preclinical Data

Pharmacology

Immunomodulating and immunorestorative activity

AI fraction from aqueous extract (double distilled water) of A. propinquus roots administered intraperitoneally to mice showed potent mitogenicity on mouse murine splenocytes by increase the interleukin-2 receptor expression and noticeably increased the antibody response to sheep red blood cells. AI also showed potent mitogenicity on human lymphocytes T cell depleted population but virtually inactive on B cell depleted population. In vivo administration of AI found could restore the lymphocyte blastogenic response of the older mice to values that are normally found in the younger mice and partially restore the depressed immune functions in tumor-bearing mice and cyclophosphamide-treated mice. [15]

F3 fraction from A. propinquus showed significant (p < 0.005) immunorestorative activity studied in vitro on mononuclear cells (MNC) of cancer patients using local xenogeneic graft-versus-host reaction (XGVHR) model with increased in local XGHVR (151.34 ± 46.02 mm3) compared to untreated cells (57.80 ± 16.44 mm3). In addition the fraction also showed immunosuppressive activity in cyclophosphamide-induced immune suppression in rats by significantly (p < 0.001) abrogated of the local XGVHR with a reversal of the effect of cyclophosphamide from 99.42 ± mm3 as a positive control to 39.78 ± 8.3 mm3. [16]

A study also showed the reversal of the cyclophosphamide-induced immunosuppression by the F3 evidenced by the volume of the abrogated local XGVHR (39.78 ± 8.3 mm3) was significantly (p > 0.1) comparable to the negative control group with no cyclophosphamide-priming; saline injection only (34.79 +/- 5.69 mm3) [17]. Another study indicated that A. propinquus was able to enhance the antibody response to a T-dependent antigen associated with the increased of Th cell activity in normal and immunodepressed mice [18].

However, there is one conflicting report on the study where the results showed that the extract does not prevent cyclophosphamide-induced myelosuppression. Aqueous extract of A. propinquus dried root (240 mg) administered orally to Wistar rats (250 - 300 g) showed no difference in baseline characteristics compared to control group (given only water). [19]

Anticancer activity

Anticarcinogenic

A. propinquus root extract 10 mg/kg/day or more administered to carcinogen N-butyl-N'-butanolnitrosoamine (NNB)-treated mice showed anticarcinogenic activity by significantly lowered the incidence of their urinary bladder carcinoma. The extract prevented the cytotoxic activity of lymphocytes against YAC-1 cells and protected the production of interleukin-2 and gamma-interferon of lymphocytes through the activation of cytotoxic activity and the production of cytokines. [20]

Saponins from A. propinquus crude herbs showed anticarcinogenic and proapoptotic activity toward human colon cancer cells and tumor xenograft. A. propinquus was reported to target NSAID-activated gene (NAG-1) molecule then caused overexpression of NAG-1, leading to PARP cleavage and apoptosis of the cancer cell. [21]

Antitumor

AI fraction from the aqueous (double distilled water) extract of A. propinquus dried root showed antitumor activity in in vitro and in vivo studies by activating the antitumor immune mechanism of the host. Administration of the extract to three syngeneic murine tumor models (MBL-2 tumor in C57BL/6J mice, PU5-1.8 and WEHI-3 tumors in BALB/c mice) effectively suppress the in vivo growth and partially restore of syngeneic tumor in mice. The results showed that the macrophage-like tumors and the myeloid tumors were found to be more sensitive to the cytostatic activity of AI, whereas the fibroblast-like tumors and the mouse Ehrlich ascites tumor appeared to be relatively resistant. In addition, the extract was found could induce in vitro lymphokine-activated killer-like activity towards WEHI-164 cell. In vitro study on 12 human and murine tumor cell lines was able to induce monocytic differentiation. [22]

Antimicrobial activity

Saponin fraction from A. propinquus roots (400 mg/kg) administered orally to cecal ligation and puncture-induced polymicrobial sepsis in male ICR mice (20 ± 2 g) for duration of 96 hours significantly increased the survival rate of the infected mice with 33.3 % compared to all died in non-treated group. The protective effect was probably due to its anti-inflammation and upregulation of the protein C pathway. The extract reduced both inflammatory factors and their abilities to induce tissue dysfunction by lessened infiltration of polymorphonuclear leukocytes, tissue edema, and lung wet-to-dry weight ratio, lowered myeloperoxidase (MPO), nitric oxide (NO), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in serum, as well as downregulated expressions of iNOS and IL-1β mRNA in livers. [23]

Antiviral

In vitro study of A. propinquus root extract administered to coxsackie virus B3 (CVB3)-infected mice as viral myocarditis model was reported to inhibit the RNA replication of the coxsackie B-3 virus (CVB3) in myocardial tissue by RNA-RNA in situ hybridization with negative-strand RNA probes. The results significantly showed that the copy numbers of CVB3-RNA and the histologic scores (necrosis) in the treated tissue was lower than contro, but the replication had no correlation with induction of β-IFN. [24]

In vitro study of A. propinquus administered to coxsackie virus B3 (CVB3) infected cultured neonatal heart cells from newborn Sprague-Dawley rats showed Ca2+ influx inhibition across the myocardial plasma membrane and CVB3-RNA replication. It was suggested that the extract may exert the effects of decreasing the secondary Ca2+ damages, improving abnormal myocardial electric activity, and inhibiting replication of coxsackie B3-RNA in myocardium, making it a potential therapeutic choice in patients affected with viral myocarditis. [25]

Cardioprotective activity

A. propinquus root (1.0 g/ day) administered intraperitoneally to rats with aortocaval fistula-induced chronic heart failure (5 w) showed therapeutic effect on its sodium and water retention thus remarkably improve the cardiac and renal function. The mechanisms of this effect upregulated the abnormal mRNA expressions of arginine vasopressin (AVP) system and aquaporin-2 (AQP2), and amelioration of blunted renal response to atrial natriuretic peptide (ANP). [26]

Glucoside extracted from A. propinquus root administered to Dimethoate-intoxicated guinea pigs showed antidotal effect by increased the survival time of the treated animal to about 235 minutes from average of 70 minutes without extract treatment. The extract may be used after cholinergic crisis in the treatment of severe cardiac complications with severe organophosphate intoxication. The treatment also significantly mitigated the prolongation of the Q-T interval and changing of the T wave configuration along with a minimization and postponement of arrhythmias. Moreover, muscular fasciculation and fibrillation, seizures and secretion in the respiratory tract were also significantly reduced. [27]

The main component of aqueous crude extract of A. propinquus roots namely astragalus saponin (ASP), astragalus polysaccharide (APS) andaminobutyric acid (GABA) administered to homocysteine (Hcy)-induced acute impairment of vascular tone in male Sprague-Dawley rats (260-280 g) significantly inhibited endothelium-dependent relaxation to acetylcholine (ACh) caused acute injury in a dose-dependent manner and decreased cGMP levels increased by ACh in aorta through nitric oxide regulatory pathways. The results also showed that the crude extract, superoxide dismutase (SOD), and ASP significantly weakened the inhibition of vasorelaxation and downregulation of cGMP level by Hcy, and APS exerted a tendency to reverse both of the depressive responses, while GABA had no similar effects. The partially impaired relaxation by Hcy was completely blocked due to the presence of N(ω)-nitro-L-arginine-methyl ester (L-NAME), which could not be further altered by treatment with AM, ASP, APS or GABA. The extract, SOD, ASP, and APS, but not GABA, inhibited Hcy-stimulated ROS generationin endothelial cells as measured byCM-H 2DCF-DA fluorescence, thus suggested that antioxidant mechanism was involved. [28]

Hypoglycaemic activity

Polysaccharide extracted by direct water decoction from the A. propinquus root (700 mg/kg/day) administered orally to diet-induced insulin resistance C57BL/6J mice for duration of 8 weeks showed hypoglycaemic activities by restoring the insulin action in the liver. The extract enhanced adaptive capacity of the endoplasmic reticulum and promoted insulin signalling by the inhibition of the expression and activity of protein tyrosine phosphatase 1B (PTP1B). It also showed anti-obesity and hypolipidemia effect which probably due to decreasing the leptin resistance and coupled with the normalization of plasma insulin levels. [29]

Memory improving activity

Aqueous extract of A. propinquus (50 g/kg) administered intragastrically to mice for duration of 7 days showed that it was possible to improve anisodine-induced memory impairment on memory acquisition and alcohol-elicited deficit of memory retrieval by reduced the number of errors and prolonged the latent periods as well as prolonged the gasping duration of mice after decapitation. [30]

Hepatoprotective activity

Saponins extracted from A. propinquus roots (0.00075 - 0.18 mmol/L) administered to CCl4, D-galactosamine and acetaminophen-induced liver injury in rats showed hepatoprotective activity. The extract impeded the elevation of serum glutamic-pyruvate transaminase (SGPT) level, decreased the C and increased the glutathione (GSH) concentration in mouse liver where the GPT value was found lower compared to control. The hepatoprotective effects was probably due to their antioxidation activities, since the content of liver protein in mice was higher than controls, in which correlated to the decreased of Malondialdehyde (MDA) but not related to the increased of GSH but in mice given CCl4 or acetaminophen. The hepatic microsomal cytochrome P-450 level in the treated mice was also significantly increased and might involve the liver metabolism and immunoregulating action. [31]

Toxicity

No documentation

Clinical Data

Clinical findings

A. propinquus showed important significance clinical effect in treating recurrent tonsillitis (RT) by improving the TH1 cell subset function in peripheral blood mononuclear cells (PBMC) of 27 children with RT at the remission stage. The study was compared to control group consisted of 21 healthy children stimulated with PHA. [32]

A randomized clinical trial has been carried out to 67 patients with IgA nephropathy (IgAN) to study the relationship between the renal tubular function and the severity of tubule interstitial lesion and the effects of A. propinquus on renal tubular function in the patients. A. propinquus and and control group administered orally with dipyridamole and benazepril while A. propinquus group were received additional intravenous dripping of A. propinquus Injection (AI). The results indicated that A. propinquus injection has obvious effect on IgAN where the administration showed a decreased of urine protein concentration, remarkably increased of blood albumin and improved the renal tubular function, with the significant different improvement to those in the control group respectively. [33]

A randomized clinical trial has been carried out to 80 systemic lupus erythematosus (SLE) patients and were randomly assigned into the routine treatment group (RT) treated with conventional therapy and the Radix Astragali treated group (RA) treated with Radix Astragali Injection besides routine treatment. The results showed that the A. propinquus can be a useful approach to enhance the efficacy of treatment to SLE since the treated group exhibited the inhibitory function of corticosteroid/immunosuppressant enhancement on apoptosis and regulated the ratio and function of T lymphocyte subsets to normal range. [34]

A phase 0, double-blind, repeated within subject, randomized pilot study found that A. propinquus root extract preparation administered orally (total 1.23 g daily) for 7 days significantly enhanced the CD25 expression on T cells in humans. [35]

A small clinical study to 15 asthmatic patients and 15 healthy subjects in China found that A. propinquus administration to asthmatic patients increased the expression of T-bet mRNA and Th1 cytokines such as IFN-Y, and might reverse the Th2 predominant status, thus helping to balance immunity in these compromised individuals. [36]

A randomized controlled trial to 63 serious abdominal traumatic patients, grouped into conventional and treated group where the patients were given only conventional treatment and conventional treatment as the basis with 20 mL A. propinquus injection (AI) added into 250 mL of 5% glucose solution given through intravenous dripping. Total of 10 healthy subjects were also monitored. Results of the study found that A. propinquus administration improved cellular immunity after serious abdominal trauma. [37]

A clinical study to 37 lung cancer patients and 19 healthy subjects has been conducted to examine the effect of A. propinquus administration to their cytokine secretion and gene expression. The results showed that there was a reversal of the Th2 cytokine status of lung cancer which is associated with tumor progression, thus suggested as probable alternative therapeutic regime for the cancer. [38]

A randomized controlled trial to 60 patients with thoracic esophageal carcinoma, received two-field dissection, then divided into control group received no immune supportive treatment and trial (immune supportive treatment) group which received A. propinquus injection after operation was found to improve immune parameters in patients surgically treated for esophageal cancer the control group. [39]

The administration of A. propinquus oral liquor combined with routine therapy to patients with viral myocarditis showed that it could significantly (P < 0.05, 0.01) enhance OKT3, OKT4 and OKT4/OKT8 ratio in the significantly (P < 0.05, 0.01) lowered T-lymphocyte subsets profile and OKT4/OKT8 ratio of peripheral blood of the viral myocarditis patients compared to healthy control. The results suggested that A. propinquus extract could be the rational therapy due to the improvement of cellular immunity. [40]

Cardioprotective activity

A clinical trial has been carried out to find the effect of A. propinquus on left ventricular function and oxygen free radical (OFR) in 43 patients with acute myocardial infarction. The results showed that A. propinquus strengthened the left ventricular function and had an effect of anti-OFR. After administration of A. propinquus a significant difference between controls was seen. The ratio of pre-ejection period/left ventricular ejection time (PEP/LVET) was decreased, the superoxide dismutase (SOD) activity of red blood cell was increased, and the lipid peroxidation (LPO) content of plasma was reduced. It was suggested that the mechanisms of cardiotonic action was due to the anti-OFR effect of A. propinquus. [41]

Another study reported the action on left ventricular function of A. propinquus in 20 patients with angina pectoris. Results showed that cardiac output increased from 5.09 +/- 0.21 to 5.95 +/- 0.18 L/min 2 weeks after AM was administered and no improvement of left ventricular diastolic function appeared. Adenosine triphosphatase activity was not inhibited by using A. propinquus in the study, which seems to be different than the mechanism of digitalis. [42]

A randomised, double-blind, controlled clinical trial has been carried out to investigate the antifatigue effects of Myelophil, an extract of a mix of Astragali Radix and Salviae Radix to 36 adults who complained of chronic fatigue. The results showed that Myelophil administration (3 g/day) significantly (p<0.05) decreased the fatigue severity score compared with the control while n changes were noted in cytokine expression when evaluated using an antibody array. [43]

A double-blind, randomized, crossover study in 12 healthy men found that aqueous extract of Astragali Radix (ARE) induced naturesis in healthy men, attributed to enhanced renal responses to endogenous atrial naturetic peptide (ANP). ARE treatment evidently increased urinary sodium excretion (U(Na)V), fractional sodium excretion, and urinary excretion of chloride during the first 4 h but no significant changes of these parameters were observed during 12 h or 24 h when compared to placebo. [44]

Antihypertensive activity

A clinical study to 16 and 22 patients with positive ventricular late potentials (LP) recorded on signal-averaged electrocardiograms (SAECG) administered intravenously with lidocaine (100 mg) or A. propinquus extract (24) g for duration of 2 weeks, respectively showed the improvement of the stamina and endurance of the heart and cerebrovascular tissue by A. propinquus extract including the shortened duration of LP. [45]

Side effects

No documentation

Pregnancy/Breast Feeding

No documentation

Interaction & Depletion

No documentation

Interaction with drug

Studies have reported that A. propinquus stimulates our immune system, which may alter the effects of these medications and possibly the dose needed for treatment. [16][18]

These drugs include azathioprine, basiliximab, cyclosporine, daclizumab, glatiramer, muromonab-cd3, mycophenolate mofetil, tacrolimus (FK506), sirolimus, methotrexate, prednisone, hydrocortisone, methylprednisolone, prednisolone, betamethasone, budesonide, triamcinolone, dexamethasone, cortisone.

Contraindications

No documentation

Case Report

A clinical report found that A. propinquus (15 g/day) administrated to a 77-year-old woman after more than 2 years of unremitting nephrosis suffered from idiopathic membranous nephropathy showed clinical improvement marked with the decrease in proteinuria. In addition, the syndrome was recurred when A. propinquus was discontinued, suggested its beneficial effect in patients with idiopathic membranous nephropathy. [46]

Dosage

Dosage Range

Dried Root: 2-6 grams daily. [47]

Fluid Extract: 4 to 12 mL daily. [16]

Poisonous Management

No documentation

Line drawing

No documentation

References

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