Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

OBJECTIVE

Asthma is recognized as a common pulmonary disease throughout the world. To date, there has been a growing interest in herbal products in Traditional Chinese Medicine, which is considered to be effective to treat asthma. A Chinese herb Astragalus Membranaceus (AM) was found useful in treating allergic diseases. The purpose of this study is to determine whether this herbal injection could suppress allergic-induced AHR and mucus hypersecretion in allergic mice.

METHODS

A mouse model of chronic asthma was used to investigate AM injection on the airway lesions in compared with glucocorticoids. The study was conducted on mice sensitized and challenged with ovalbumin and the whole body plethsmography was performed to assess AHR. The bronchoalveolar lavage (BAL), histopathology were examined.

RESULTS

We found 28-day AM administration significantly decreased inflammatory infiltration and mucus secretion in the lung tissues of allergic mice. 28-day AM administration enhanced Ova-induced decreased IFN-gamma, and the Ova-induced elevations of IL-5 and IL-13 in BALF were prevented by 28-day injection. We also showed 28-day AM injection markedly suppressed increased AHR in allergic mice.

CONCLUSIONS

Our results indicate Astragalus Membranaceus has a potential role in treating allergic asthma.

OBJECTIVE

To investigate the effects of components isolated from Astragalus membranaceus on myocardial ischemia reperfusion injury.

METHODS

The myocardial ischemia reperfusion injury model was created by the left anterior descending coronary artery occlusion from the oracotouated rats, and the total saponins, total flavonids and astragaloside i.v. isolated from A. membranaceus on hemodynamics during acute myocardial ischemia, Na(+)-K(+)-ATPase activity, cAMP and malondialdehyede (MDA) contents in the ischemic myocardium were observed.

RESULTS

The total saponins, total flavonids and astragaloside i.v. attenuated the declines of the amplitudes of LVSP and +/- LVdp/dtmax in rat heart injured by ischemia reperfusion in vivo, and decreased Na(+)-K(+)-ATPase activity in the ischemic myocardium. Otherwise, the total saponins increased the cAMP content and the total flavonids decreased the level of MDA production in the ischemic myocardium.

CONCLUSIONS

The effects of different components isolated from A. membranaceus on protecting the cardiac function in the process of ischemia reperfusion may be related to the mechanism of improving energy metabolism, scavenging the oxygen free radicals and inhibiting the production of free radicals in the ischemic myocardium.

The study was designed to investigate efficacy and safety of Astragalus membranaceus (AM) in the treatment of patients with seasonal allergic rhinitis (SAR). AM is an active component in the herbal and mineral complex (HMC) registered in Croatia as a food supplement Lectranal. The study was designed as a 6-weeks, double-blind, placebo-controlled clinical trial and conducted in 48 adult patients with a moderate to severe SAR. The treatment efficacy was evaluated by the mean change in the symptom score (TSS), quality of life (QoL), specific serum IgE and IgG, nasal eosinophils, and physicians' and patients' global evaluation. Compared to placebo, HMC significantly decreased the intensity of rhinorrhea while for other primary efficacy variables the treatment groups did not differ. In contrast, investigators and patients equally judged the treatment with HMC as more efficacious. In addition, the analysis of changes from baseline inside the groups for TSS, QoL, and 4 main symptoms of SAR were strikingly in favor of the active treatment. In patients with SAR due to weed pollen allergy HMC significantly improved primary variables, reflective TSS and QoL. The study revealed a significant number of positive signals indicating the therapeutic effectiveness of the HMC in patients with SAR which should be further tested in larger, multicentre trials with more patients.

Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus-treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.

Apoptosis with premature termination of hair follicle growth induces several types of hair loss and is one of the crucial factors of hair loss. Astragaloside IV, which is a major component of Astragalus membranaceus, is a cycloartane triterpene saponin. Although an anti-apoptotic effect of Astragaloside IV has been reported, its effects against hair loss have not been investigated. To explore the underlying mechanisms of Astragaloside IV on apoptotic signaling in hair follicle, the dorsal skin of depilated C57BL/6 mice was topically treated with 1 and 100 μM Astragaloside IV for 14 days. In Astragaloside IV-treated group, TUNEL-positive cells were reduced. We found that Astragaloside IV blocked the procaspase-8, resulting in the inhibition of caspase-3 and procaspase-9 activities. The changes were accompanied with down-regulation of Bax and p53, and up-regulation of Bcl-2 and Bcl-xL by Astragaloside IV treatment. In addition, activation of NF-κB and phosphorylation of IκB-α were inhibited, along with decreases in three MAPKs: ERK, SAPK/JNK and p38 by Astragaloside IV. The expressions of KGF, p21, TNF-α and IL-1β, which are keratinocyte terminal differentiation markers associated with catagen, were modulated by treatment with Astragaloside IV. These results demonstrated that Astragaloside IV is concerned with blocking the Fas/Fas L-mediated apoptotic pathway, which would be an alternative therapy for hair loss.

We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor κB (NF-κB)/Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-κB/PGC-1α signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1α, inhibited translocation of p65, subunit of NF-κB into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1α expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.

BACKGROUND

Astragaloside IV is the primary pure saponin isolated from Astragalus membranaceus, one of the valuable traditional medical herbs. Antifibrotic activities of Astragalus membranaceus have been extensively proved.

OBJECTIVE

To investigate the effects of astragaloside IV on hepatic stellate cells (HSCs) and hepatic fibrosis in rats induced by porcine-serum (PS).

METHODS

Liver fibrosis was induced by PS injection (0.5 ml, twice a week) for 12 weeks. Astragaloside IV (2.0, 4.0 mg kg(-1)) was administered intragastrically. Liver samples were subjected to histological and immunohistochemical studies. In vitro effects of astragaloside IV on primary cultured HSCs were detected by incorporation assays.

RESULTS

Astragaloside IV delayed the formation of liver fibrosis and decrease the serum levels of hyaluronic acid (HA), procollagen type III (PCIII) and hydroxyproline (Hyp) content in liver. The levels of transforming growth factor-beta(1) (TGF-beta(1)) in serum and expression in liver were significantly decreased by astragaloside IV. Collagen synthesis and proliferation were significantly inhibited by astragaloside IV (1.5, 3.0, 6.0, 12.0 and 24.0 mg L(-1)) in HSCs.

CONCLUSIONS

The results showed that astragaloside IV displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its inhibitory effects on collagen synthesis and proliferation in HSCs.

A total of 108 crossbred piglets (7.75 +/- 0.24 kg of BW) weaned at 28 d was used to study the interactive effects of beta-glucan obtained from the Chinese herb Astragalus membranaceus (AM) and Escherichia coli lipopolysaccharide (LPS) challenge on performance, immunological, adrenal, and somatotropic responses of weaned pigs. The treatments were in a 2 x 3 factorial arrangement; main effects were level of Astragalus membranaceus glucan (AMG; 0, 500, or 1,000 mg/kg; as-fed basis) and presence of immunological challenge (with or without LPS). The experiment included six replicate pens per treatment and three pigs per pen. Lipopolysaccharide challenges were conducted on d 7 and 21 of the trial. Blood samples were obtained from the vena cava from one pig per pen at 3 h after LPS challenge to determine plasma responses. Weight gain and feed:gain ratio were unaffected by glucan. However, there was a quadratic effect on feed intake (P < 0.05): pigs fed 500 mg of glucan/kg had the highest feed intake. Immunological challenge with LPS decreased weight gain (P = 0.02). An interaction (P = 0.01 to 0.09) between AMG and LPS was observed for glucose, IL-1beta, PGE2, and cortisol. Astragalus membranaceus glucan had a quadratic effect on the plasma concentrations of glucose, IL-1beta, PGE2, and cortisol (P < 0.05) after both LPS challenges. Plasma concentrations of glucose, IL-1beta, PGE2, and cortisol (P < 0.05) were all increased in LPS-challenged pigs compared with the control pigs after both LPS challenges. The IGF-I concentrations were less for LPS-challenged pigs than for unchallenged pigs. The lymphocyte proliferation response of peripheral blood induced by 5 microg of concanavalin A/mL (P < 0.01) and IL-2 bioactivity (P < 0.05) increased linearly with increasing addition of glucan. Pigs challenged with LPS had greater T-lymphocyte proliferation (P = 0.06) and IL-2 bioactivity (P = 0.07) than unchallenged pigs after the first immunological challenge but not after the second. In conclusion, although glucan did not improve pig performance under the conditions of the present experiment, when included at 500 mg/kg, it decreased the release of inflammatory cytokine and corticosteroid and improved the lymphocyte proliferation response of weanling piglets via enhanced IL-2 bioactivity.

BACKGROUND

The root of Astragalus membranaceus, known as "huang-qi", is one of the most widely used Chinese herbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown.

OBJECTIVE

The aims of the present study were to investigate the cardioprotective effect of the root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro.

METHODS

The saponins in EAM were analyzed using HPLC. The tests for the cardioprotective effects of EAM and its mechanisms were performed in vivo and in vitro. In vivo, the rat model of persistent myocardial ischemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the direct free radical donor, H2O2.

RESULTS

In vivo, the increased myocardial infarct size and the increased serum levels of lactate dehydrogenase (LDH), creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as assessed by±dP/dt, left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP), was dramatically improved. An oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2-triggered myocardial cell death and cytoplasm Ca(2+) overload were blocked by treatment with EAM. Furthermore, the KATP channel blocker (5-HD, glibenclamide) blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by H2O2.

CONCLUSIONS

The cardioprotection of EAM was manifested as a protection of tissue structure and as a decrease in serum markers of ischemic injury. The mechanisms underlying the EAM-mediated protective effects may involve improving cardiac function, attenuating the oxidative injury via a decrease in MDA, a maintenance in SOD, and a reduction in free radical-induced myocardial cell injury. Additionally, EAM enhanced the myocardial cell viability via arresting the influx of Ca(2+) to block cell death and opening mitochondrial KATP channels to reduce cell apoptosis.

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.

The purpose of the present study was to examine the effects of astragaloside IV, a saponin isolated from Astragalus membranaceus (Fisch) Bge, on the impairment of barrier function induced by acute high glucose in cultured human vein endothelial cells. High glucose (27.8 mM) induced a decrease in transendothelial electrical impedance and an increase in cell monolayer permeability in human umbilical vein endothelial cells. Endothelial barrier dysfunction stimulated by high glucose was accompanied by translocation and activation of protein kinase C (PKC), the redistribution of F-actin and formation of intercellular gaps, suggesting that increases in PKC activity and rearrangement of F-actin could be associated with endothelial barrier dysfunction induced by acute high glucose. Application of astragaloside IV inhibited high glucose-induced endothelial barrier dysfunction in a dose-dependent manner, which is compatible with inhibition of PKC translocation and improvement of F-actin rearrangements. Western blot analysis revealed that high glucose-induced PKC alpha and beta2 overexpression in the membrane fraction were significantly reduced by astragaloside IV. These findings indicate that astragaloside IV protected endothelial cells from high glucose-induced barrier impairment by inhibiting PKC activation, as well as improving cytoskeleton remodeling.

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.

OBJECTIVE

Recently, plant lectins have attracted great interest due to their various biological activities such as anti-cancer, anti-fungal and anti-viral activities. We have reported earlier concerning anti-proliferation of human cancer cell lines by a galactose-binding lectin (AML), from a Chinese herb, ASTRAGALUS MEMBRANACEUS: In the present study, detailed investigations into the mechanism of such anti-proliferation properties have been carried out.

METHODS

Mechanism of apoptosis initiation in K562 cells by AML was investigated by morphology, flow cytometry and western blot analysis.

RESULTS

AML induced apoptosis in a caspase-dependent manner in the chronic myeloid leukemia cell line, K562. Furthermore, we observed that cytotoxicity and apoptosis of K562 cells induced by AML were completely abolished in presence of lactose or galactose.

CONCLUSIONS

Our results suggest that AML could act as a potential anti-cancer drug.

This study was designed to identify and characterize the immune receptors for polysaccharides from Ganoderma lucidum, a Chinese medicinal fungus that exhibits anti-tumor activities via enhancing host immunity. We herein demonstrate that G. lucidum polysaccharides (GLPS) activated BALB/c mouse B cells and macrophages, but not T cells, in vitro. However, GLPS was unable to activate splenic B cells from C3H/HeJ mice that have a mutated TLR4 molecule (incapable of signal transduction) in proliferation assays. Rat anti-mouse TLR4 monoclonal antibody (Ab) inhibited the proliferation of BALB/c mouse B cells under GLPS stimulation. Combination of Abs against mouse TLR4 and immunoglobulin (Ig) achieved almost complete inhibition of GLPS-induced B cell proliferation, implying that both membrane Ig and TLR4 are required for GLPS-mediated B cell activation. In addition, GLPS significantly inhibited the binding of mouse peritoneal macrophages with polysaccharides from Astragalus membranaceus, which is known to bind directly with TLR4 on macrophage surface. Moreover, GLPS induced IL-1beta production by peritoneal macrophages from BALB/c, but not C3H/HeJ, mice, suggesting that TLR4 is also involved in GLPS-mediated macrophage activation. We Further identified a unique 31 kDa serum protein and two intracellular proteins (ribosomal protein S7 and a transcriptional coactivator) capable of binding with GLPS in co-precipitation experiments. Our results may have important implications for our understanding on the molecular mechanisms of immunopotentiating polysaccharides from traditional Chinese medicine.

BACKGROUND

The identification of eligible controlled trials for systematic reviews of complementary and alternative medicine (CAM) interventions can be difficult. To increase access to these difficult to locate trials, the Cochrane Collaboration Complementary Medicine Field (CAM Field) has established a specialized register of citations of CAM controlled trials. The objective of this study is to describe the sources and characteristics of citations included in the CAM Field specialized register.

METHODS

Between 2006 and 2011, regular searches for citations of CAM trials in MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were supplemented with contributions of controlled trial citations from international collaborators. The specialized register was 'frozen' for analysis in 2011, and frequencies were calculated for publication date, language, journal, presence in MEDLINE, type of intervention, and type of medical condition.

RESULTS

The CAM Field specialized register increased in size from under 5,000 controlled trial citations in 2006 to 44,840 citations in 2011. Most citations (60%) were from 2000 or later, and the majority (71%) were reported in English; the next most common language was Chinese (23%). The journals with the greatest number of citations were CAM journals published in Chinese and non-CAM nutrition journals published in English. More than one-third of register citations (36%) were not indexed in MEDLINE. The most common CAM intervention type in the register was non-vitamin, non-mineral dietary supplements (e.g., glucosamine, fish oil) (34%), followed by Chinese herbal medicines (e.g., Astragalus membranaceus, Schisandra chinensis) (27%).

CONCLUSIONS

The availability of the CAM Field specialized register presents both opportunities and challenges for CAM systematic reviewers. While the register provides access to thousands of difficult to locate trial citations, many of these trials are of low quality and may overestimate treatment effects. When including these trials in systematic reviews, adequate analysis of their risk of bias is of utmost importance.

Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson's staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF.

Astragalus membranaceus, dried root extract, also known as Astragali radix, is used in traditional Chinese medicine as a tonic remedy. Moreover, it has been reported that Astragalus membranaceus could attenuate intestinal inflammation; however, the underlying mechanism for its anti-inflammatory activity in intestinal epithelial cells (IECs) remains unclear. In this study, we evaluated Astragalus membranaceus extract (5-100 µg/mL) in a model of inflammation and oxidative stress for IECs. We showed that Astragalus membranaceus extract reduced the inflammatory response induced by lipopolysaccharide from E. coli (LPS) plus interferon-γ (IFN), decreasing tumor necrosis factor-α (TNF-α) release, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, nitrotyrosine formation, nuclear factor-κB (NF-κB) activation, and reactive oxygen species (ROS) release in the non-tumorigenic intestinal epithelial cell line (IEC-6). The antioxidant potential of Astragalus membranaceus extract was also evaluated in a model of hydrogen peroxide (H₂O₂)-induced oxidative stress in IEC-6, indicating that this extract reduced ROS release and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and the expression of antioxidant cytoprotective factors in these cells. The results contributed to clarify the mechanisms involved in Astragalus membranaceus extract-reduced inflammation and highlighted the potential use of this extract as an anti-inflammatory and antioxidant remedy for intestinal diseases.

BACKGROUND

Chemoresistance is a major obstacle to successful chemotherapy for human non-small cell lung cancer (NSCLC). Astragaloside IV, the component of Astragalus membranaceus, has been reported to exhibit anti-inflammation, anti-cancer and immunoregulatory properties. In the present study, we investigated the role of astragaloside IV in the chemoresistance to cisplatin in NSCLC cells.

METHODS

We established astragaloside IV-suppressed NSCLC cell lines including A549, HCC827, and NCI-H1299 and evaluated their sensitivity to cisplatin in vitro. In addition, we examined the mRNA and protein levels of B7-H3 in response to cisplatin-based chemotherapy.

RESULTS

We showed that high doses of astragaloside IV (10, 20, 40 ng/ml) inhibited NSCLC cell growth, whereas low concentrations of astragaloside IV (1, 2.5, 5 ng/ml) had no obvious cytotoxicity on cell viability. Moreover, combined treatment with astragaloside IV significantly increased chemosensitivity to cisplatin in NSCLC cells. On the molecular level, astragaloside IV co-treatment significantly inhibited the mRNA and protein levels of B7-H3 in the presence of cisplatin. In addition, ectopic expression of B7-H3 diminished the sensitization role of astragaloside IV in cellular responses to cisplatin in NSCLC cells.

CONCLUSIONS

These results demonstrate that astragaloside IV enhances chemosensitivity to cisplatin via inhibition of B7-H3 and that treatment with astragaloside IV and inhibition of B7-H3 serve as potential therapeutic approach for lung cancer patients.

OBJECTIVE

Tumor cells have developed multiple mechanisms to escape immune recognition mediated by T cells. Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme inducing immune tolerance, is involved in tumor escape from host immune systems in mice. Astragaloside IV (AS-IV), an extract from a commonly used Chinese medicinal plant Astragalus membranaceus, has been shown to be capable of restoring the impaired T-cell functions in cancer patients. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of AS-IV.

METHODS

Here, we used IDO-overexpressed murine Lewis lung carcinoma cells to establish an orthotopic lung cancer model in C57BL/6 mice. Next, tumor growth was evaluated in several different treatment groups: control (saline), AS-IV, paclitaxel, and 1-methyl tryptophan (an inhibitor of IDO). We then analyzed the percentages of various immune cell subsets among the splenic lymphocytes of lung cancer mice by flow cytometry. The level of IDO was measured by real-time PCR and Western blot.

RESULTS

We showed that the growth of tumor was suppressed by AS-IV treatment in vivo. AS-IV also could down-regulate regulatory T cells (Tregs) and up-regulate cytotoxic T lymphocytes (CTLs) in vivo and in vitro. Consistent with its ability to interfere with T-cell immunity, AS-IV blocked IDO induction both in vitro and in vivo.

CONCLUSIONS

The results of these studies indicate that AS-IV has in vivo anticancer activity and can enhance the immune response by inhibiting the Tregs frequency and induce the activity of CTLs, which might be related to the inhibition of IDO expression.

BACKGROUND

Astragalus membranaceus and Salvia miltiorrhiza have been used for centuries in China to treat liver diseases. Previous studies have shown that these herbs and their extracts inhibit the development of liver fibrosis and the proliferation and invasion of human hepatoma HepG2 cells. Further study of their pharmacological effects on hepatocellular carcinoma (HCC) is needed. To investigate the effects of Compound Astragalus and Salvia miltiorrhiza Extract (CASE) on diethylinitrosamine (DEN)-induced hepatocarcinogenesis in rats.

METHODS

Male rats were divided into five groups, with the first group serving as normal control, the second group receiving 0.2% DEN solution five times a week for 14 weeks, and the third to fifth group receiving the same DEN as in the second group together with CASE at the doses of 60, 120, and 240 mg/kg per day for 16 weeks, respectively. Hepatoma incidence, serum enzymes levels, degree of fibrosis and hydroxyproline content were evaluated and compared across the five groups to determine CASE's suppression of fibrosis and HCC progression. In addition, an in vitro experiment using HepG2 cells was conduct to verify CASE's effect on the transcription of plasminogen activator inhibitor-1 (PAI-1) mRNA.

RESULTS

CASE treatment significantly reduced the incidence and multiplicity of DEN-induced HCC development in a dose-dependent manner. It significantly suppressed the elevation of alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, hyaluronic acid, direct bilirubin and total bilirubin, and significantly lessened the depression of serum total protein in DEN-induced HCC rats. CASE treatment also significantly suppressed the elevated expression of GST-P and α-SMA. The in vitro experiment confirmed that CASE inhibits the transcription of PAI-1 mRNA in HepG2 cells induced by TGF-β1 in a dose-dependent manner.

CONCLUSIONS

CASE suppresses DEN-induced hepatocarcinogenesis by inhibiting fibrosis and PAI-1 mRNA transcription, suggesting its potential clinical application in preventing and treating human HCC.

Diabetic nephropathy, a microvascular complication of diabetes, is a progressive kidney disease caused by angiopathy of the capillaries in the kidney glomeruli. Herein, we report a case of a 62-year-old patient with a 30 year history of diabetes, who showed a substantial improvement in diabetic nephropathy on administration of 30 g of Astragalus membranaceus extract per day. After 1 month, estimated glomerular filtration rate increased from 47 to 72 ml/min per 1.73 m(2) and was subsequently maintained at the 1-month follow-up. Urinary protein levels also decreased following treatment. Herein, we present and discuss the evidence and mechanism of A. membranaceus on diabetic nephropathy in this patient.

CONCLUSIONS

Diabetic nephropathy is a progressive kidney disease.Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are currently used to prevent and delay the progression of diabetic nephropathy. However, their effects are not sufficient to prevent a decline in kidney function.Furthermore, combination therapy with an ACE inhibitor and an ARB can produce adverse effects without additional benefits.In the early phase of diabetic nephropathy, administration of Astragalus membranaceus can be a therapeutic option.

Oxidative stress and neuroinflammation are the key and early events during the pathological process of Parkinson's disease (PD). Thus, therapeutic intervention to regulate oxidative stress and neuroinflammation would be an effective strategy to alleviate the progression of PD. Astragaloside IV, the main active component isolated from Astragalus membranaceus, has been shown to possess anti-inflammatory and anti-oxidant properties in neurodegeneration diseases, however, the molecular mechanisms of Astragaloside IV in the pathology of PD are still unclear. In this study, we explored the mechanisms of Astragaloside IV of PD on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model and lipopolysaccharide (LPS)-induced BV2 microglia cells. Our results showed Astragaloside IV significantly alleviated behavioral impairments and dopaminergic neuron degeneration induced by MPTP. Also, Astragaloside IV inhibited microglia activation and reduced the oxidative stress of MPTP mouse model. In addition, Astragaloside IV significantly inhibited NFκB mediated NLRP3 inflammasome activation and activated Nrf2 both in vivo and in vitro. Furthermore, Astragaloside IV lessened reactive oxygen species (ROS) generation in LPS-induced BV2 microglia cells remarkably. These findings demonstrate that Astragaloside IV protects dopaminergic neuron from neuroinflammation and oxidative stress which are largely dependent upon activation of the Nrf2 pathways and suppression of NFκB/NLRP3 inflammasome signaling pathway. Therefore, Astragaloside IV is a promising neuroprotective agent that should be further developed for neurodegeneration diseases.