Astragalus
Selected from ~300 articles. 

Ahmed MS. Hou SH. Battaglia MC. Picken MM. Leehey DJ. Treatment of idiopathic membranous nephropathy with the herb Astragalus membranaceus. American Journal of Kidney Diseases. 50(6):1028-32, 2007 A 77-year-old woman with nephrotic syndrome secondary to idiopathic membranous nephropathy was treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, cyclosporine A, and mycophenolate mofetil, without response. After more than 2 years of unremitting nephrosis, she began therapy with the herb Astragalus membranaceus, used by traditional Chinese physicians to treat various immune disorders, including glomerulonephritis. After institution of Astragalus at a dose of 15 g/d, there was a marked decrease in proteinuria. Nephrotic syndrome recurred after temporary cessation of Astragalus therapy, with complete remission of nephrosis observed after its reintroduction. The clinical course of this patient suggests that Astragalus may have beneficial effects in patients with idiopathic membranous nephropathy. 

Lee SJ. Oh SG. Seo SW. Ahn HJ. Geum D. Cho JJ. Park CS. Oral administration of Astragalus membranaceus inhibits the development of DNFB-induced dermatitis in NC/Nga mice. Biological & Pharmaceutical Bulletin. 30(8):1468-71, 2007 Epicutaneously administered chemical antigens like 2,4-dinitrofluorobenzene (DNFB), evoke an atopic dermatitis (AD)-like dermatitis reaction in NC/Nga mice under specific pathogen free (SPF) conditions. Astragalus membranaceus (AM), is a popular herbal medicine used to treat allergic diseases in East Asia. In the present study, we examined whether AM suppress AD-like skin lesions in NC/Nga mice treated with DNFB under SPF conditions. Oral administration of AM to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. Moreover, IFN-gamma production by CD4(+) T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by AM treatment, although levels of IL-4 and total IgE in serum were not. Study findings suggest that AM may suppress the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IFN-gamma production. 

Cho WC. Leung KN. In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. Journal of Ethnopharmacology. 113(1):132-41, 2007 Astragalus membranaceus is a common traditional Chinese medicinal plant widely used as a tonic to enhance the body's natural defense mechanisms. In this study, bioactive fractions were isolated from the roots of Astragalus membranaceus. One of these fractions, designated as AI, was found to be the most potent with respect to its mitogenicity on murine splenocytes. Effects of AI on both specific and nonspecific immunity in mouse models were examined. Results showed that AI could exhibit mitogenic and co-mitogenic activities on mouse splenocytes, both in vitro and in vivo. Experiments in human cell culture demonstrated that AI was also active on human lymphocytes. It was found that AI was mitogenic to T cell depleted population but virtually inactive on B cell depleted population. Intraperitoneal injection of AI into mice markedly augmented the antibody response to sheep red blood cells. Besides, both the influx of macrophages into the peritoneal cavity and the phagocytic activity of macrophages were found to be enhanced by AI in vivo. On the other hand, AI could significantly increase the interleukin-2 receptor expression on mouse splenocytes in vitro. In terms of immunorestorative activity, it was found that AI could restore the lymphocyte blastogenic response of the older mice to values that are normally found in the younger mice. Moreover, administration of AI in vivo could partially restore the depressed immune functions in tumour-bearing mice and cyclophosphamide-treated mice. Collectively, the results clearly showed that AI could exhibit immunomodulating and immunorestorative effects, both in vitro and in vivo. 

Cho WC. Leung KN. In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cancer Letters. 252(1):43-54, 2007 Astragalus membranaceus, a commonly used Chinese medicinal plant, has been shown to be capable of restoring the impaired T cell functions in cancer patients. In this study, the in vitro and in vivo anti-tumor effects of A. membranaceus were investigated. Five bioactive fractions were isolated from the root of A. membranaceus, the fraction designated as AI was found to be the most potent among the five fractions with respect to its mitogenicity on murine splenocytes. Besides investigating the cytostatic effect of AI, its activities on macrophage function, tumor necrosis factor production, induction of lymphokine-activated killer cell and tumor cell differentiation were also examined. 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. Moreover, AI could effectively suppress the in vivo growth of syngeneic tumor in mice. Results showed that murine macrophage pretreated with AI had increased in vitro and in vivo cytostatic activities towards MBL-2 tumor. AI could also act as a priming agent for tumor necrosis factor production in tumor-bearing mice. Preincubation of mouse splenocytes with AI could induce in vitro lymphokine-activated killer-like activity towards WEHI-164 cell. Furthermore, AI was able to induce monocytic differentiation of both human and murine cells in vitro. AI administered in vivo could even partially restore the depressed mitogenic response in tumor-bearing mice. Collectively, the results showed that A. membranaceus could exhibit both in vitro and in vivo anti-tumor effects, which might be achieved through activating the anti-tumor immune mechanism of the host. 

Li RJ. Qiu SD. Chen HX. Tian H. Wang HX. The immunotherapeutic effects of Astragalus polysaccharide in type 1 diabetic mice. Biological & Pharmaceutical Bulletin. 30(3):470-6, 2007 The present study investigated whether Astragalus polysaccharide (APS) possessed immunotherapeutic effects on type 1 diabetes mellitus. Diabetic mice induced by multiple low dose streptozotocin (MLD-STZ) were administered either APS (100, 200, 400 mg/kg body weight) or saline intraperitoneally daily, and sacrificed after 15 or 30 d of treatment. Meanwhile normal mice not treated with STZ nor with APS were offered into non-diabetic group. Blood glucose and serum insulin levels were measured, histologic and morphometric analyses of the pancreas were performed to determine the effect of APS on pancreatic islets. Further investigations on immune changes in spleens were tested by ELISA, semi-quantitative RT-PCR and Western blot. Downregulated blood glucose level, upregulated serum insulin concentration, increased beta cell mass, decreased apoptotic beta cell percentage, downregulation of Th1/Th2 cytokine ratio and upregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression in spleens were significantly time- and dose-dependent on APS treatment, when compared to saline controls. These results show that APS seems to be helpful to attenuate insulitis and preserve beta cells from apoptosis, but it can't entirely rescue type 1 diabetes mellitus. APS ameliorates both the clinical and histological parameters of the MLD-STZ induced diabetic mice in a long-lasting fashion, most likely through immunoregulatory actions on Th1/Th2 cytokine ratio, strongly associated with PPARgamma gene expression in spleens. 

Zhang BQ. Hu SJ. Qiu LH. Zhu JH. Xie XJ. Sun J. Zhu ZH. Xia Q. Bian K. Effects of Astragalus membranaceus and its main components on the acute phase endothelial dysfunction induced by homocysteine. Vascular Pharmacology. 46(4):278-85, 2007 OBJECTIVE: This study was designed to investigate the effects of Astragalus membranaceus (AM) and its main components, astragalus saponin (ASP), astragalus polysaccharide (APS) and aminobutyric acid (GABA), on homocysteine (Hcy) induced acute impairment of vascular tone and to explore whether the antioxidant mechanism was involved in AM protective effect. METHODS: Inhibitory effects of Hcy and protective effects of AM and its main components on endothelium-dependent relaxation of aortic rings were determined by isometric tension recordings and nitric oxide signaling was assayed with 125I-cGMP RIA Kit. Furthermore, generation of reactive oxygen species (ROS) in endothelial cells was detected using 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCF-DA). RESULTS: Hcy significantly inhibited endothelium-dependent relaxation to acetylcholine (ACh) in a dose-dependent manner, and decreased cGMP levels increased by ACh in aorta. Furthermore, superoxide dismutase (SOD), AM, and ASP markedly attenuated 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. Additionally, partially impaired relaxation by Hcy was completely blocked due to the presence of N(omega)-nitro-L-arginine-methyl ester (L-NAME), which could not be further altered by treatment with AM, ASP, APS or GABA. Finally, Hcy significantly increased intracellular ROS levels in endothelial cells as measured by CM-H2DCF-DA fluorescence. SOD, AM, ASP, and APS, but not GABA, inhibited Hcy-stimulated ROS generation. CONCLUSION: This study demonstrated that AM and ASP, potently protected endothelium-dependent relaxation against the acute injury from Hcy through nitric oxide regulatory pathways, in which antioxidation played a key role. 

Li S. Zhang Y. Zhao J. Preparation and suppressive effect of astragalus polysaccharide in glomerulonephritis rats. International Immunopharmacology. 7(1):23-8, 2007 Astragalus membranaceus (AM) has been widely used for treating kidney diseases in traditional Chinese medicine. In this study, the Astragalus polysaccharide (APS), the main active ingredient was isolated and purified from the Rhizomes of AM, which consisted of d-glucopyranose and had the molecular weight of 3.6x10(4) Da. The effect of APS on glomerulonephritis rats induced by cationic Bovine Serum Albumin(C-BSA) was evaluated by flow cytometry using Nuclear Transcription Factor-kappaB (NF-kappaB) as marker. Interleukin-2 (IL-2), Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha) were determined by the ELISA method. The rats (model group and treatment group) were injected subcutaneously with C-BSA plus incomplete Freund's adjuvant on day 0, C-BSA was injected through the caudal vein from week 2 to week 7 to induce glomerulonephritis. The rats (treatment group) were given APS by intraperitoneal injection from week 2 to week 7. The expression of NF-kappaB and the concentration of IL-2, IL-6 and TNF-alpha were significantly decreased in the treatment group. This study clearly suggests that APS is effective in protecting against glomerulonephritis induced by C-BSA through the inhibition of NF-kappaB mediated-cytokine pathway. 

Wang G. Liu CT. Wang ZL. Yan CL. Luo FM. Wang L. Li TQ. Effects of Astragalus membranaceus in promoting T-helper cell type 1 polarization and interferon-gamma production by up-regulating T-bet expression in patients with asthma. Chinese Journal of Integrative Medicine. 12(4):262-7, 2006 OBJECTIVE: To explore the effect of Astragalus membranaceus (AM) on T-helper cell type 1 (Thl) specific transcription factor T-box expressed in T cells (T-bet) expression and Thl/Th2 equilibrium. METHODS: The levels of T-bet mRNA in peripheral blood mononuclear cells (PBMCs) from 15 patients with asthma and 15 healthy subjects were determined by reverse transcription-polymerase chain reaction (RT-PCR). PBMCs in asthma patients were incubated with AM and then the concentration of interferon gamma (IFN-gamma) and interleukin-4 (IL-4) in the supernate before and after AM intervention were determined by ELISA. The numbers of CD4 + CCR3 + and CD4 + CCR5 + cells were counted by flow cytometry. RESULTS: The expression of T-bet mRNA and the level of IFN-gamma were lower, but level of serum IL-4 was higher in asthma patients when compared with those in healthy subjects respectively. After AM (60 microg/ml) intervention, the former two parameters raised and showed a positive correlation between them, while the level of IL-4 was decreased. The mean percentage of CD4 + CCR3 + cells in asthma patients was significantly higher but that of CD4 + CCR5 + cells was lower when compared with those in healthy subjects respectively. After AM intervention, the abnormal change in the two indexes was improved to certain extent, showing a reversing status of Th2 polarization. CONCLUSION: AM could increase the expression of T-bet mRNA and Thl cytokines such as IFN-Y, and might reverse the Th2 predominant status in asthma patients. 

Chen XJ. Meng D. Feng L. Bian YY. Li P. Yang D. Cao KJ. Zhang JN. Protective effect of astragalosides on myocardial injury by isoproterenol in SD rats. American Journal of Chinese Medicine. 34(6):1015-25, 2006. We have extracted and roughly purified astragalosides (AS) from Astragalus membranaceus, a natural herb used as a traditional Chinese medicine, regarded to have pharmacodynamic benefits of protecting injured myocardium. We hypothesized that the astragalosides might exert beneficial effect in myocardial lesion by preserving both energy metabolism and Ca(2+) homeostasis. Sprague-Dauley (SD) rats were injected with isoproterenol (ISO) subcutaneous (s.c.) at a dose of 5 mg/kg/day consecutively for two days as models and were treated with astragalosides and trimetazidine intraperitoneally (i.p.) respectively, at a dose of 5 mg/kg/day one day prior to isoproterenol for 8 days. The histological changes were alleviated in isoproterenol-injected SD rats treated with astragalosides. Compared with isoproterenol-injected rats, the concentration of myocardial intracellular [Ca(2+)]i was decreased, L-type Ca(2+) current density and sarcoplasmic reticulum (SR) Ca(2+) load were recovered, the concentration of myocardial ATP was increased and phosphocreatine (PCr) was decreased in rats treated with astragalosides. In conclusion, the efficacious treatment of astragalosides for myocardial injury might be through regulating intracellular Ca(2+) homeostasis and energy metabolism. 

Gan XL. Hei ZQ. Huang HQ. Chen LX. Li SR. Cai J. Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats. Chinese Medical Journal. 119(22):1892-8, 2006 BACKGROUND: The mechanism of mucosal damage induced by ischemia-reperfusion (IR) after hemorrhagic shock is complex; mast cells (MC) degranulation is associated with the mucosal damage. Astragalus membranaceus can protect intestinal mucosa against intestinal oxidative damage after hemorrhagic shock, and some antioxidant agents could prevent MC against degranulation. This study aimed to observe the effects of astragalus membranaceus injection on the activity of intestinal mucosal mast cells (IMMC) after hemorrhage shock-reperfusion in rats. METHODS: Thirty-two Wistar rats were randomly divided into the normal group, model group, low dosage group, (treated with Astragalus membranacaus injection, 10 g crude medication/kg) and high dosage group (treated with Astragalus membranacaus injection, 20 g crude medication/kg). The rat model of hemorrhagic shock-reperfusion was induced by hemorrhage for 60 minutes followed by 90 minutes of reperfusion. The animals were administrated with 3 ml of the test drug solution before reperfusion. At the end of study, intestinal pathology, ultrastructure of IMMC, and expression of tryptase were assayed. The levels of malondisldehyde (MDA), TNF-alpha, histamine, and superoxide dismutase (SOD) activity in intestine were detected, and the number of IMMC was counted. RESULTS: The Chiu's score of the rats in the model group was higher than in other groups (P < 0.01). The Chiu's score in the high dosage group was higher than that in the low dosage group (P < 0.05). Hemorrhage-reperfusion induced IMMC degranulation: Astragalus membranaceus injection attenuated this degranulation. Expression of tryptase and the number of IMMC in the model group increased compared with the other groups (P < 0.01) and was significantly reduced by the treatments of Astragalus membranaceus injection at both doses. There was no significant difference between the two treatment groups (P > 0.05). MDA content and concentration of TNF-alpha in the model group were higher than that in the other three groups (P < 0.05), and the concentration of TNF-alpha in the low dosage group was higher than that in the high dosage group (P < 0.05). SOD activity and the concentration of histamine in the model group were lower than the other three groups (P < 0.05). There was a negative correlation between the Chiu's score and the concentration of histamine and a positive correlation between the Chiu's score and the concentration of TNF-alpha and between the SOD activity and the concentration of histamine in the four groups (P < 0.05). CONCLUSION: Astragalus membranaceus injection may reduce the damage to small intestine mucosa by inhibiting the activated IMMC after hemorrhagic shock. 

Wu XL. Wang YY. Cheng J. Zhao YY. Calcium channel blocking activity of calycosin, a major active component of Astragali Radix, on rat aorta. Acta Pharmacologica Sinica. 27(8):1007-12, 2006 AIM: To investigate the vasoactivity of calycosin, a major active component of Astragali Radix. METHODS: Experiments were performed on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PHE) or KCl. RESULTS: Calycosin produced a concentration-dependent relaxation on the tissue pre-contracted using PHE with 4.46+/-0.13 of pD(2) and 95.85%+/-2.67% of E(max); or using KCl with 4.27+/-0.05 of pD2 and 99.06%+/-2.15% of Emax, and displaced downwards the concentration-response curves of aortic rings to PHE or KCl. The relaxant effect of calycosin on denuded endothelium aortic rings was the same as on intact endothelium aortic rings, and its vasorelaxant effect was not influenced by L-NAME or indomethacin. In Ca(2+)-free solution, calycosin (30 micromol/L) did not have an effect on PHE (1 micromol/L)-induced aortic ring contraction. The effects of calycosin and nifedipine where somewhat different; calycosin decreased aortic ring contractions induced by the two agonists, but nifedipine displayed a more potent inhibitory effect on KCl-induced contractions than on PHE-induced contractions, and the vascular relaxing effects of calycosin and nifidipine were additive on PHE-induced contraction but not KCl-induced. CONCLUSION: Calycosin is a vasorelaxant. Its action is endothelium-independent and is unrelated to intracellular Ca(2+) release. It is a noncompetitive Ca(2+) channel blocker. The effect of calycosin on Ca(2+) channel blockade may be different from that of dihydropyridines. This study demonstrated a novel pharmacological activity of calycosin, and supplied a theoretic foundation for Astragali Radix application. 

Li X. He D. Zhang L. Cheng X. Sheng B. Luo Y. A novel antioxidant agent, astragalosides, prevents shock wave-induced renal oxidative injury in rabbits. Urological Research. 34(4):277-82, 2006 Extracorporeal shock-wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms, including small vessel injury and free radical formation. Our previous studies have demonstrated that Astragalus membranaceus (AM), a traditional Chinese herb, could significantly alleviate shock wave-induced renal oxidative injury, and its renoprotective effects were superior to those of varapamil, a calcium antagonist, which were considered to be a powerful agent in treating renal damage during ESWL. However, the effective antioxidant ingredient of this herb in the setting of lithotripsy remains unclear. Astragalosides, the major components of AM, was demonstrated to have superior antioxidation properties both in vitro and in vivo. Therefore, in this study we further investigate the potential effects of astragalosides on the shock wave-induced oxidative stress in rabbit kidney. Thirty male rabbits were randomly assigned to two groups, each consisting of 15 rabbits: (1) control group, (2) astragaloside-treated group. Each group of animals underwent 1,500 shock waves to the right kidney. Peripheral blood, urine and kidney tissue samples were collected pre- and post-ESWL. The level of urinary N-acetyl-beta-glucosaminidase (NAG), serum creatinine, serum or homogenates malondialdehyde (MDA) and superoxide dismutase (SOD), respectively, were detected. Histological alterations were also examined through light microcopy and transmission electron microscopy. In the control group, shock wave significantly increased the level of MDA and decreased SOD activity in both blood and renal homogenates (P<0.05, respectively). The comparison between the control and astragalosides group demonstrated that astragalosides could significantly decrease the level of MDA (P<0.05) and inhibit the decline of SOD activity (P<0.05). After exposure to shock waves, the activity of urinary NAG increased significantly in the control group (P<0.05). However, the concentration of serum creatinine did not change significantly. The comparison between the control and astragalosides group demonstrated that astragalosides significantly reduced the shock wave-induced leakage of NAG into the urine (P<0.05). Histological examination also showed that renal morphological impairments were much milder in astragaloside-treated rabbits than those of the control group. Our results indicated that astragaloside treatment provided significant protection against shock wave-induced renal oxidative injury. 

Xu F. Zhang Y. Xiao S. Lu X. Yang D. Yang X. Li C. Shang M. Tu P. Cai S. Absorption and metabolism of Astragali radix decoction: in silico, in vitro, and a case study in vivo. Drug Metabolism & Disposition. 34(6):913-24, 2006 To profile absorption of Astragali Radix decoction and identify its orally absorbable constituents and their metabolites, four complementary in silico, in vitro, and in vivo methods, i.e., a computational chemistry prediction method, a Caco-2 cell monolayer model experiment, an improved rat everted gut sac experiment, and a healthy human volunteer experiment, were used. According to the in silico computation result, 26 compounds of Astragali Radix could be regarded as orally available compounds, including 12 flavonoids. In the in vitro and in vivo experiments, 21 compounds were tentatively identified by high-performance liquid chromatography-diode array detection-electrospray ion trap tandem mass spectrometry data, which involved calycosin, formononetin, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, calycosin-7-O-beta-D-glucoside, formononetin-7-O-beta-D-glucoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside-6''-O-malonate, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside, and phase II metabolites calycosin-7-O-beta-D-glucuronide, formononetin-7-O-beta-D-glucuronide, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucuronide, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucuronide, and calycosin sulfate. Calycosin and formononetin were proved absorbable by four methods; (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan and 7,2'-dihydroxy-3',4'-dimethoxyisoflavan were proved absorbable by three methods; formononetin-7-O-beta-D-glucoside and (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside were proved absorbable by two methods. The existence of calycosin-7-O-beta-D-glucuronide, formononetin-7-O-beta-D-glucuronide, (6aR,11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucuronide, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucuronide, and calycosin sulfate was proved by two or three methods. We found that besides isoflavones, pterocarpans and isoflavans also could be metabolized by the intestine during absorption, and the major metabolites were glucuronides. In conclusion, the present study demonstrated that the flavonoids in Astragali Radix decoction, including isoflavones, pterocarpans, and isoflavans, could be absorbed and metabolized by the intestine. These absorbable compounds, which were reported to have various bioactivities related to the curative effects of Astragali Radix decoction, could be regarded as an important component of the effective constituents of Astragali Radix decoction. 

Shen P. Liu MH. Ng TY. Chan YH. Yong EL. Differential effects of isoflavones, from Astragalus membranaceus and Pueraria thomsonii, on the activation of PPARalpha, PPARgamma, and adipocyte differentiation in vitro. Journal of Nutrition. 136(4):899-905, 2006 Compounds that target the peroxisome proliferator-activated receptors PPARalpha and PPARgamma are used to correct dyslipidemia and to restore glycemic balance, respectively. Because the majority of diabetic patients suffer from atherogenic lipid abnormalities, in addition to insulin resistance, ligands are required that can activate both PPARalpha and PPARgamma. In this study, we used chimeric PPARalpha/gamma reporter-gene bioassays to screen herbal extracts with purported antidiabetic properties. Extracts of Astragalus membranaceus and Pueraria thomsonii significantly activated PPARalpha and PPARgamma. Bioassay-guided fractionation resulted in the isolation of the isoflavones, formononetin, and calycosin from Astragalus membranaceus, and daidzein from Pueraria thomsonii as the PPAR-activating compounds. We investigated the effects of these and 2 common isoflavones, genistein and biochanin A, using chimeric and full-length PPAR constructs in vitro. Biochanin A and formononectin were potent activators of both PPAR receptors (EC50 = 1-4 micromol/L) with PPARalpha/PPARgamma activity ratios of 1:3 in the chimeric and almost 1:1 in the full-length assay, comparable to those observed for synthetic dual PPAR-activating compounds under pharmaceutical development. There was a subtle hierarchy of PPARalpha/gamma activities, indicating that biochanin A, formononetin, and genistein were more potent than calycosin and daidzein in chimeric as well as full-length receptor assays. At low doses, only biochanin A and formononetin, but not genistein, calycosin, or daidzein, activated PPARgamma-driven reporter-gene activity and induced differentiation of 3T3-L1 preadipocytes. Our data suggest the potential value of isoflavones, especially biochanin A and their parent botanicals, as antidiabetic agents and for use in regulating lipid metabolism. 

Zhang YW. Xie D. Xia B. Zhen RT. Liu IM. Cheng JT. Suppression of transforming growth factor-beta1 gene expression by Danggui buxue tang, a traditional Chinese herbal preparation, in retarding the progress of renal damage in streptozotocin-induced diabetic rats. Hormone & Metabolic Research. 38(2):82-8, 2006 Danggui buxue tang (DBT), a preparation containing Angelica sinensis (danggui) and Astragalus membranaceus (huangqi) at a ratio of 1 : 5, is used widely in China for stimulating red blood cell production and enhancing cardiovascular function. The present study was undertaken to characterize the effects of this preparation on diabetic nephropathy using streptozotocin-diabetic rats as a model. Streptozotocin-dependent alterations in renal weight/body weight ratio, urinary albumin and beta (2)-microglobulin concentrations, urinary albumin excretion rate, and creatinine clearance were ameliorated after eight weeks of treatment with either DBT or the angiotensin-converting enzyme inhibitor, benazepril. DBT, but not benazepril, partially attenuated the increases in blood glucose, triglycerides and cholesterol in STZ-diabetic rats. Additionally, the increased expression of transforming growth factor-beta (1) mRNA in the renal cortex due to streptozotocin-induced diabetes was modestly attenuated by these treatments. However, eight weeks of treatment with DBT failed to modify the concentration of angiotensin II in plasma or kidney, indicating that the ability of the preparation to retard the progression of kidney disease was not attributable to inhibition of the renin-angiotensin system. We propose that DBT alleviates renal alterations in diabetes and slows the progression of diabetic nephropathy by suppressing transforming growth factor-beta (1) mRNA expression. The preparation may therefore be useful as an adjuvant therapy for controlling diabetes and its complications. 

Zhang WD. Chen H. Zhang C. Liu RH. Li HL. Chen HZ. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro. Planta Medica. 72(1):4-8, 2006 Astragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of cardiovascular diseases in China. However, the effects of astragaloside IV on myocardial ischemia and its mechanisms of action remain largely unknown. In this study, we have examined the effects of astragaloside IV on myocardial infarction and coronary flow in vivo and in vitro. The possible roles of its antioxidative and nitric oxide-inducing properties were also explored. Astragaloside IV significantly reduced infarct size in dogs subjected to coronary ligation in vivo. Astragaloside IV also improved post-ischemic heart function and ameliorated reperfusion arrhythmias in rat hearts in vitro. The cardioprotection of astragaloside IV was accompanied by a significant increase in coronary flow both in vivo and in vitro. The nitric oxide synthase inhibitor, Nomega-nitro- L-arginine methyl ester partially abrogated astragaloside IV's protective effect on heart function. Myocardial antioxidative enzyme superoxide dismutase activity increased with astragaloside IV administration. These data suggest the potential roles of antioxidative and nitric oxide-inducing properties of astragaloside IV in its protection from myocardial ischemia. 

Xu ME. Xiao SZ. Sun YH. Ou-Yang Y. Zheng XX. Effects of astragaloside IV on pathogenesis of metabolic syndrome in vitro. Acta Pharmacologica Sinica. 27(2):229-36, 2006 AIM: To investigate the diverse pharmacological actions of astragaloside IV from the perspective of metabolic syndrome, and to investigate the effect of the drug on the pathogenesis of metabolic syndrome. METHODS: Adipogenesis was used as an indicator of the effect of astragaloside IV on preadipocyte differentiation, and was measured by using an oil red O assay. Glucose uptake was determined by measuring the transport of [2-(3)H]-deoxyglucose into the cells. The concentrations of peroxisome proliferator-activated receptor-gamma (PPARgamma) and aP2 mRNA were determined by using reverse transcription-polymerase chain reaction. Apoptosis and viability loss of endothelial cells were detected by using flow cytometry and the WST-1 assay, respectively. Intracellular free Ca2+ was labeled with Fluo-3 AM and measured by using a laser scanning confocal microscope. RESULTS: Astragaloside IV can significantly potentiate insulin-induced preadipocyte differentiation at concentrations of 3, 10, and 30 microg/mL, improve high glucose-induced insulin resistance in adipocytes at a concentration of 30 microg/mL, and prevent tumor necrosis factor (TNF)-alpha-induced apoptosis and viability loss at concentrations of 10 and 30 microg/mL, and 30 microg/mL, respectively, in endothelial cells. Furthermore, we found that these effects were partly due to the promotion of PPARgamma expression and to the inhibition of abnormal TNF-alpha-induced intracellular free Ca(2+) accumulation in endothelial cells. CONCLUSION: The diverse pharmacological actions of astragaloside IV can all be linked to metabolic syndrome pathogenesis. Our study provides a new insight into the mechanism by which astragaloside IV exerts its effect. 

Ko JK. Lam FY. Cheung AP. Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis. World Journal of Gastroenterology. 11(37):5787-94, 2005 AIM: To investigate the protective effects of Astragalus membranaceus (Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism. METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o. twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis. RESULTS: Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression. Besides, deprivation of colonic GSH level under colitis condition was also preserved. CONCLUSION: These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues. 

Yang ZG. Sun HX. Fang WH. Haemolytic activities and adjuvant effect of Astragalus membranaceus saponins (AMS) on the immune responses to ovalbumin in mice. Vaccine. 23(44):5196-203, 2005 In this study, the haemolytic activities of Astragalus membranaceus saponins (AMS) and its adjuvant potentials on the cellular and humoral immune responses of ICR mice against OVA were evaluated. We determined the haemolytic activity of AMS using 0.5% rabbit red blood cell. AMS showed a slight haemolytic effect, with its haemolytic percent being 0.66% at the concentration of 500 microg/ml. Furthermore, the adjuvant potentials of AMS at three dose levels on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA) were investigated. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing Alum (200 microg), QuilA (10 and 20 microg) or AMS (50, 100 or 200 microg) on Day 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. AMS significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice especially at a dose of 100 microg (P<0.05 or P<0.001). OVA-specific IgG, IgG1 and IgG2b antibody titers in serum were also significantly enhanced by AMS compared with OVA control group (P<0.01 or P<0.001). Moreover, no significant differences (P>0.05) were observed between enhancing effect of AMS and QuilA on the OVA-specific IgG, IgG1 and IgG2b antibody responses to OVA in mice. In conclusion, the results suggest that AMS could be safely used as adjuvant with low or non-haemolytic effect. 

Hei ZQ. Huang HQ. Zhang JJ. Chen BX. Li XY. Protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury after hemorrhagic shock in rats. World Journal of Gastroenterology. 11(32):4986-91, 2005 AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats. METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group, model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL) was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined. RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group, slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group. CONCLUSION: High dose Astragalus membranaeus has much better protective effect on hemorrhagic shock-reperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion. 

Lee KY. Jeon YJ. Macrophage activation by polysaccharide isolated from Astragalus membranaceus. International Immunopharmacology. 5(7-8):1225-33, 2005 We show that APS, a polysaccharide isolated from the roots of Astragalus membranaceus, significantly induces nitric oxide (NO) production and inducible NO synthase (iNOS) transcription through the activation of nuclear factor-kappaB/Rel (NF-kappaB/Rel). In vivo administration of APS induced NO production by peritoneal macrophages of B6C3F1 mice. APS also dose-dependently induced the production of NO in isolated mouse peritoneal macrophages and RAW 264.7, a mouse macrophage-like cell line. Moreover, iNOS protein and mRNA transcription were strongly induced by APS in RAW 264.7 cells. To further investigate the mechanism responsible for the induction of iNOS gene expression, we investigated the effect of APS on the activation of transcription factors including NF-kappaB/Rel and Oct, whose binding sites were located in the promoter of iNOS gene. Treatment of RAW 264.7 cells with APS produced strong induction of NF-kappaB/Rel-dependent reporter gene expression, whereas Oct-dependent gene expression was not affected by APS. Nuclear translocation and DNA binding activity of NF-kappaB/Rel was significantly induced by APS. The treatment with NF-kappaB SN50, an inhibitor of NF-kappaB/Rel nuclear translocation, effectively inhibited the activation of NF-kappaB/Rel binding complexes and NO production. In conclusion, we demonstrate that APS stimulates macrophages to express iNOS gene through the activation of NF-kappaB/Rel. 

Wu Y. Ou-Yang JP. Wu K. Wang Y. Zhou YF. Wen CY. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B. Acta Pharmacologica Sinica. 26(3):345-52, 2005 AIM: To examine the effects of Astragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance. METHODS: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type II diabetes mellitus (TIIDM), were treated with APS (400 mg/kg p.o.) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit. RESULTS: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle, but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle, but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS. CONCLUSION: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats. 

Shao BM. Xu W. Dai H. Tu P. Li Z. Gao XM. A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochemical & Biophysical Research Communications. 320(4):1103-11, 2004 The immunopotentiating effect of the roots of Astragalus membranaceus, a medicinal herb, has been associated with its polysaccharide fractions (Astragalus polysaccharides, APS). We herein demonstrate that APS activates mouse B cells and macrophages, but not T cells, in terms of proliferation or cytokine production. Fluorescence-labeled APS (fl-APS) was able to selectively stain murine B cells, macrophages and a also human tumor cell line, THP-1, as determined in flow cytometric analysis and confocal laser scanning microscopy. The specific binding of APS to B cells and macrophages was competitively inhibited by bacterial lipopolysaccharides. Rabbit-anti-mouse immunoglobulin (Ig) antibody was able to inhibit APS-induced proliferation of, and APS binding to, mouse B cells. Additionally, APS effectively stimulated the proliferation of splenic B cells from C3H/HeJ mice that have a mutated TLR4 molecule incapable of signal transduction. These results indicate that APS activates B cells via membrane Ig in a TLR4-independent manner. Interestingly, macrophages from C3H/HeJ mice were unable to respond to APS stimulation, suggesting a positive involvement of the TLR4 molecule in APS-mediated macrophage activation. Monoclonal Ab against mouse TLR4 partially inhibited APS binding with macrophages, implying direct interaction between APS and TLR4 on cell surface. These results may have important implications for our understanding on the molecular mechanisms of immunopotentiating polysaccharides from medicinal herbs. 

Lei H. Wang B. Li WP. Yang Y. Zhou AW. Chen MZ. Anti-aging effect of astragalosides and its mechanism of action. Acta Pharmacologica Sinica. 24(3):230-4, 2003 AIM: To study the anti-aging effect of astragalosides (AST) and its mechanism of action. METHODS: Rotating rod test and step-down type passive avoidance test were performed to determine the effects of AST on motor and memory of D-galactose (D-gal)-induced senescent mice and the middle-aged mice. The proliferative response of splenocytes induced by Con A or LPS, IL-2 production of splenocytes induced by ConA of D-gal-treated mice and the middle-aged mice were also measured. RESULTS: AST (40 mg.kg(-1).d(-1), ig, for 10 weeks) was found to ameliorate age-related alternations in both motor response and memory, enhance the deteriorated cellular immunity in D-gal-treated mice and the pre-aged (17-month-old) mice. CONCLUSION: AST has an anti-aging effect on D-gal-induced senescent mice and has the effect of delaying senility of the middle-aged mice, which was related to its improvement of brain function and immunomodulatory effects. 

Cui R. He J. Wang B. Zhang F. Chen G. Yin S. Shen H. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemotherapy & Pharmacology. 51(1):75-80, 2003 Astragalus membranaceus (AM) has been widely used for treating liver diseases in traditional Chinese medicine. Experimental evidence indicates that it has antitumor potential. In this study, the effect of AM on hepatocarcinogenesis induced by diethylnitrosamine (DEN), two-thirds partial hepatectomy, and 2-acetylaminofluorene (2-AAF) (DEN-PH-AAF) was evaluated using glutathione S-transferase placenta form (GST-P) as marker. First, rats were injected intraperitoneally (i.p.) with DEN (200 mg/kg in saline), a two-thirds partial hepatectomy was carried out 2 weeks later, and the rats were then placed on a basal diet containing 0.02% AAF from week 3 to week 8 to induce hepatocarcinogenesis. The rats were given AM (90 mg/kg or 180 mg/kg body weight) by gavage from week 3 to week 8 (treatment groups). The formation of GST-P-positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF were reduced in the treatment groups, which clearly suggests that AM is effective in delaying DEN-PH-AAF-induced hepatocarcinogenesis. 

Toda S. Yase Y. Shirataki Y. Inhibitory effects of astragali radix, crude drug in Oriental medicines on lipid peroxidation and protein oxidative modification of mouse brain homogenate by copper. Phytotherapy Research. 14(4):294-6, 2000 Astragali Radix, the root of Astragalus membranaceus Bunge, is a crude drug used widely in Oriental medicines. It is a major component of Ougi-Keishi-gomotsu-to, a traditional herbal medicine, used for neurop patients with abnormal sensations and neuropathic pain of the legs. It was shown to have inhibitory effects on lipid peroxidation and protein oxidative modification by copper. The effects were similar to and stronger than those of mannitol and superoxide dismutase as free radical scavengers. These results demonstrated that Astragali Radix has inhibitory effects on oxidative stress induced by metal. 

Yim TK. Wu WK. Pak WF. Mak DH. Liang SM. Ko KM. Myocardial protection against ischaemia-reperfusion injury by a Polygonum multiflorum extract supplemented 'Dang-Gui decoction for enriching blood', a compound formulation, ex vivo. Phytotherapy Research. 14(3):195-9, 2000 'Dang-Gui Decoction for Enriching the Blood' (BE), a traditional Chinese formulation comprising Angelica sinensis and Astragalus membranaceus, is used for stimulating red blood cell production as well as enhancing cardiovascular function. In the present study, we have demonstrated the myocardial protection afforded by BE pretreatment against ischaemia-reperfusion (IR) injury in isolated-perfused rat hearts. A more complete and potent myocardial protection against IR injury was also shown by a Polygonum multiflorum extract supplemented BE preparation (BEA). The results suggest that the more potent cardioprotective action of BEA may be related to its ability to sustain the myocardial glutathione antioxidant status under conditions of IR-induced oxidative stress, which may possibly in turn result from the synergistic interaction between the BE and Polygonum extract. 

Ma J. Peng A. Lin S. Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure. Chinese Medical Journal. 111(1):17-23, 1998 OBJECTIVE: To investigate the therapeutic effect of Astragali on sodium and water retention in aortocaval fistula-caused experimental congestive heart failure and its involved mechanisms. METHODS: In aortocaval fistula-caused chronic (5 wk), heart failure rats treated with and without Astragali 1.0 g/day intraperitoneally, changes of cardiac and renal function, renal response to atrial natriuretic peptide (ANP) were examined. Dot blot analysis was used to determine the effect of Astragali on hypothalamic arginine vasopresin (AVP) mRNA expression, and mRNA expressions of aortic and renal AVP V1a receptor, renal AVP V2 receptor and aquaporin-2 (AQP2) were simultaneously detected by RT-PCR method. RESULTS: Rats with aortocaval fistula impaired cardiac and renal functions evidenced by higher right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), lower + dP/dtmax of left ventricle, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume (UV), urinary sodium excretion (UNaV) and free water clearance (CH2O) compared with sham-operated control (P < 0.05). There was no change in serum sodium, hematocrit and plasma osmolality. Astragali could remarkably improve the cardiac and renal functions. Dot blot analysis demonstrated upregulated hypothalamic AVP mRNA expression in this experimental heart failure. The AVP V1a receptor mRNA level of aortic arch and renal medulla were reduced, while in renal cortex it was elevated. The mRNA expressions of AVP V2 receptor and AQP2 were increased in renal cortex while decreased in medulla. Astragali could partially or completely correct those abnormal mRNA expressions. Analysis on plasma atrial natriuretic peptide (ANP), urinary cyclic guanidino monophosphate excretion (UcGMP V), urinary cyclic guanidino monophosphate excretion/plasma atrial natriuretic peptide (UcGMP V/pANP), and further correlation and linear regression analysis between UcGMP V and plasma ANP showed that there was blunted renal response to ANP in heart failure rat, and astragali could improve the renal reaction to ANP significantly. CONCLUSION: Chinese herb, astragali have therapeutic effects on sodium and water retention in aortocaval fistula-induced heart failure, the mechanisms of which might be the improvement of cardiac and renal functions, partly correction of abnormal mRNA expressions of AVP system and AQP2, and amelioration of blunted renal response to ANP.