Pharmacology and Ethnomedicine of the Genus Astragalus

The genus Astragalus, consisting of about 3000 species, is a valuable source of herbal drugs. The review article comprises scientific data concerning morphological, distribution and phytochemical characters of the genus. Polysaccharides, saponins, and flavonoids are considered main active principles. Astragalus spp. have long been used as medicinal plants in folk medicine as cardiovascular, antihypertensive, diuretic, choleretic, as well as antimicrobial and antiviral agents. The plants of the genus exhibit a broad spectrum of pharmacological effects, among which major include diuretic, anti-inflammatory, bactericidal, hypotensive, and sedative ones. The review focuses on uses of about 30 Astragalus species in official medicine and ethnomedicine and their pharmacological action.

kidneys, decreases the level of residual nitrogen, urea and creatinine in blood, and increases diuresis. Since 1998, Flaronin is successfully applied to treat chronic renal insufficiency caused by pyelonephritis and other kidney diseases [12].

SPECIES OF THE GENUS ASTRAGALUS, APPLIED IN FOLK MEDICINE
Plants of the genus Astragalus have long been used as medicinal plants in folk medicine of numerous countries as cardiovascular, antihypertensive, diuretic, choleretic, as well as antimicrobial and antiviral remedies [2,26].

Astragalus adsurgens Pall.
A. adsurgens is used in Russian and Tibetan folk medicine as a diuretic remedy in oedema; in Transbaicalian regions the species is considered a wound-healing agent. The plant is also applied for labour stimulation and acceleration of separation of the placenta in gynecology [33].

Astragalus alopecias Pall.
The powdered herb of A. alopecias is applied as a wound-healing agent due to its drying properties and as a baby powder [33].

Astragalus arenarius L.
A. arenarius is used in Belarus for treatment of heart and gastrointestinal disorders; its aqueous alcohol extracts from above-ground portion possessed antibacterial and antifungal activity under experimental investigations [26].

Astragalus brachyceras Ledeb. (A. hamosus auct)
Roots of A. brachyceras are applied in the Caucasus as a diuretic and its fruits -as a coffee substitute. The fruits in mountainous parts of Turkmenistan and Iran are used as a vomiting remedy and ingredients of laxative herbal collections [26].

Astragalus cicer L.
The aboveground portion of A. cicer is used for the heart and gastrointestinal diseases in Belarus. The plant has hypotensive, diuretic, bactericidal and sedative effects, causes tachycardia, stimulates breathing, depresses the central nervous system, exhibits cholinolytic and cholesterol-lowering properties, reduces the content of lipoproteins in the blood, adrenaline and noradrenaline in the tissues [2,26].

Astragalus corniculatus Bieb.
A. corniculatus is used by Bulgarian folk medicine as a diuretic for treatment of hypertension, renal disorder, nervous diseases and rheumatism, and also as a diaphoretic [11]. Preparation of hydrogel tablets based on polyethylene oxide with standardized dry extract of A. corniculatus was developed [5]. Investigations of the ethyl acetate extract obtained from the species Astragalus corniculatus _ resulted in a low acute oral toxicity and a remarkable antihypoxic activity, especially in a model of circulatory hypoxia [15]. Effect of purified saponins' mixture (PSM) from Astragalus corniculatus on toxicity models in isolated rat hepatocytes was determined [23]. The PSM showed in vivo hepatoprotective and antioxidant activities against carbon tetrachloride (CCl 4 ) and paracetamol -induced liver damage comparable to that of silymarin [38]. In conditions of nonenzyme and enzyme lipid peroxidation in isolated rat microsomes, the PSM showed statistically significant antioxidative effect, similar to the effect of silymarin. In rat brain synaptosomes PMS had statistically significant protective effect, similar to those of silymarin on 6-hydroxydopamine-induced oxidative stress. In CCl 4 -induced toxicity, PSM had statistically significant cytoprotective and antioxidant activity. In model of oxidative stress -induced by tert-butylhydroperoxide (t-BuOOH), PSM had statistically significant

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cytoprotective and antioxidant activity, stronger than the effect of silymarin [22]. The study [30] evaluated the effect of PSM on enzyme-induced and non-enzyme-induced lipid peroxidation, in liver microsomes from spontaneously hypertensive rats (SHRs), as compared to normotensive Wistar rats (NTRs). PSM, isolated from Astragalus corniculatus, shows antioxidant activity both in SHRs and NTRs and the effect in NTRs is more pronounced. Immunorestoration and augmentation of mitogen lymphocyte response in Graffi tumor bearing hamsters by PSM from Astragalus corniculatus was observed [36]. Influence of its PSM on phagocytic cells in Graffi tumor bearing hamsters was studied [35]. Protective effect of Astragalus corniculatus saponins against myeloid Graffi tumor in hamsters was shown [18]. Phytochemical analysis of volatiles from Astragalus corniculatus were carried and in vitro cytotoxic activity investigated [17].

Astragalus corrugatus Bert.
Fruits of A. corrugatus are applied as a vomiting and laxative remedy in the Tibetan medicine [33].

Astragalus dahuricus DC.
A. dahuricus is known in the Russian and Tibetan medicine as the agent for treatment of oedema and acceleration of labours [33].

Astragalus danicus Retz.
A. danicus is used in gynecological diseases in the Altai. Its infusions have tonic and restorative properties and are used in the Middle Urals and Western Siberia for women's diseases and as a means of relieving fatigue and in cases of high blood pressure and headache on the Russian Far East [2,26].

Astragalus exscapus L.
A. exscapus is used in folk medicine of France and in Odessa region of Ukraine for treatment of syphilis, rheumatism, skin disorders, joint pain, and as a diuretic and a sudoriphic agents [33].

Astragalus fruticosus Pall. (A. suffruticosus DC.)
A. fruticosus is applied in the Russian folk medicine as a diuretic remedy [33].

Astragalus glycyphylloides DC.
A. glycyphylloides is used to stimulate labour and accelerate separation of the placenta in gynecology and as a lactogenic remedy [33]. In the Caucasus, it is used as a laxative. From its herb is obtained preparation of lactogenic properties [2,26]. The antioxidant effect of aqueous -ethanolic extract (100 mg/kg) from Astragalus glycyphylloides and its protection against carbon tetrachloride-induced oxidative stress and hepatotoxicity was shown in male Wistar rats [29]. Ethanol extract from Astragalus glycyphylloides (10 μg/mL and 100 μg/mL) had statistically significant cytoprotective and antioxidant activity, near to those of silymarin, on carbon tetrachloride (CCl 4 )-induced cytotoxicity (model of metabolic bioactivation) in isolated rat hepatocytes [14].

Astragalus glycyphyllos L.
A. glycyphyllos has an application as the emollient, diuretic, and refreshing agent in France. Its decoction is used in Bulgaria for gastroenteritis, flatulence, hypertension, sciatica, as a lactogenic agent, and as a component of herbal collection for varicose dermatitis [2,26]. The leaves and seeds of A. glycyphyllos are used in urolithiasis, oliguria, scrofula, dermatitis, and as a laxative in the Caucasus. The plant is applied in the treatment of nervous diseases in the Volga region. A decoction of the aboveground parts is used in Belarus to treat uteroptosis, leukorrhea, stomach diseases, dysentery; and externally in cases of fungal scalp infection [2,26].

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The herb in a decoction form is used in Ukraine as a laxative, diuretic, expectorant, as well as in dermatitis, sexually transmitted diseases, rheumatism. The decoction of its above-ground portion is applied in the Carpathians as diuretic in urolithiasis and other diseases of the kidneys and urinary tract; as expectorant in acute respiratory diseases; for the treatment of rheumatism, arthralgia, diarrhea, dermatitis, syphilis; to stimulate labour and accelerate separation of the placenta in gynecology [2,26]. 10% infusion of A. glycyphyllos showed hypotensive and anticoagulant effects in clinical trials. The plant infusion exhibited diuretic properties; its aqueous alcohol extracts -antibacterial and anti-Trichomonas activity; the ether extract in vitro -anti-tumor effects; the leaf extract demonstrated yeast-static action under the experimental conditions [2,26]. Currently, the plant A. glycyphyllos is regarded acting pharmacologically as A. dasyanthus and a promising source of vitamin-mineral complex and antioxidant biologically active compounds [2,20].

Astragalus hamosus L.
A. hamosus has been used traditionally for treatment of painful and inflammatory conditions. Also it is used for treatment of some nervous diseases in Iranian traditional medicine [1]. Its roots are used as a diuretic remedy [33]. The plant is demulcent, emollient, galactogogue and laxative. It is useful in treating irritation of the mucous membranes, nervous affections and catarrh [3]. Hydroalcoholic extract of the Astragalus hamosus possesses anti-nociceptive and anti-inflammatory properties which are probably mediated via inhibition of prostaglandin synthesis as well as central inhibitory mechanisms [1]. Acute anti-inflammatory activity of the methanol extract of A.hamosus has been reported [1,10]. Pharmacological evaluations have shown antioxidant activity of methanolic extract of Astragalus hamosus [32]. The antineoplastic activity of erufosine (alkylphoshocholine derivate) and the saponin mixture, derived from A. hamosus were found to be active against human leukemia cells; the saponin mixture showed dramatic decrease in the expression level of the mitochondrial protein BclxL, which outlines its special influence on the cell death signal transduction [6]. Evaluation of antiproliferative effect of a flavonol glycoside and saponins of Astragalus hamosus showed concentration-dependent inhibition of malignant cell proliferation by saponins, while the flavonoid exerted only marginal effects [16]; some of these compounds showed biological effect modulators of lymphocyte proliferation [24, ] [Verotta L,]. Volatile compounds of the plant showed significant cytotoxic activity against human acute lymphoid leukemia in concentration-dependent manner [24].

Astragalus melilotoides Pall.
Decoctions of A. melilotoides are used for treatment of scare in children and as a diuretic [33].

Astragalus monspessulanus L.
The roots of A. monspessulanus are applied in the European countries as a diuretic, sudoriphic in treatment of rheumatism, gout, dermatitis, syphilis [26]. The plant is used in Southern Italy as a diuretic [9].

Astragalus montanus Lim.
A.montanus is used as an astringent and diuretic medicine, and for cleaning of wounds and gums [33].

Astragalus onobrychis L.
A. onobrychis is applied for treatment of gynecological diseases in the Altai. Flavonoids' totality of its leaf extract shows lipid-lowering and fungistatic activity under the experimental investigations [2,26]. Immunomodulating effect of triterpenoid saponins from Astragalus onobrychis was shown [21].

Astragalus ponticus Pall.
A. ponticus is used as a diuretic for treatment of hypertension, renal disorder, nervous diseases and rheumatism, and also as a diaphoretic by Bulgarian folk medicine [11].

Astragalus sieversianus Pall.
Seeds of A. sieversianus are used internally in the Russian and Arabian folk medicine in nervous disorders, hernias in children [33].

Astragalus uliginosus L.
A. uliginosus is applied for treatment of oedema and to accelerate the labour activity [33].

Astragalus vesicarius auct. (A.albidus Waldst. et Kit.)
A. vesicarius is applied by Bulgarian folk medicine as a diuretic for treatment of hypertension, renal disorder, nervous diseases and rheumatism, and as a diaphoretic [11].

CONCLUSION
Considering that almost all of the herbs used in modern scientific medicine were derived from traditional medicine, attention to such data often has an essential impact on the effectiveness in the search of promising herbal drugs. Studying the experience of folk medicine may be one of leading methods for the search of new official medicinal plant materials. The presented scientific data might be useful for optimization both in application of official plants of the genus Astragalus in current phytotherapeutical practice worldwide and also pharmaceutical development of new phytopharmaceuticals, based on the most promising herbal substances, derived from Astragalus spp.