OBJECTIVE

To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng (, YPF) Powder and its components in rats.

METHODS

A rat chronic bronchitis (CB) model was developed using lipopolysaccharide (LPS) combined with bacillus Calmette Guerin (BCG). YPF, simple recipe Astragalus membranaceus (Fisch.) Bge (AM) and Astragalus membranaceus (Fisch.) Bge plus rhizome of Atractylodes macrocephala Koidz (AM+RA) decoction were administered (intragastric administration, once a day for 21 days) to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM+RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats.

RESULTS

Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM+RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM+RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve (AUE) of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM+RA group inhibited interleukin-8 (IL-8) in the cell culture media, and the effect was much better in the YPF group compared with AM or AM+RA group, with a higher maximal effect (Emax, P<0.05) and larger AUE (P <0.01 and P<0.05). Moreover, serum from rats treated with AM or AM+RA had similar efficacy, while the efficiency was lower than that treated with YPF.

CONCLUSIONS

YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and timedependent relationships were demonstrated in vitro.

We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers.

BACKGROUND

Herbal medicines are being used for treating viral diseases including viral myocarditis, and many controlled trials have been done to investigate their efficacy.

OBJECTIVE

To assess the effects of herbal medicines on clinical and indirect outcomes in patients with viral myocarditis.

METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library 2003, Issue 3, MEDLINE (January 1966 to October 2003), EMBASE (January 1998 to October 2003), Chinese Biomedical Database (1979-2003), AMED (1985-2003), LILACS accessed in October 2003 and the trials register of the Cochrane Complementary Medicine Field. We handsearched Chinese journals and conference proceedings. No language or publication restrictions were used.

METHODS

Randomised controlled trials of herbal medicines (with a minimum of seven days treatment duration) compared with placebo, no intervention, or conventional interventions were included. Trials of herbal medicine plus conventional drug versus drug alone were also included.

METHODS

Two reviewers independently extracted data and evaluated trial quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials.

RESULTS

Forty randomised trials, involving 3448 people were included. All trials were conducted and published in China, and the methodological quality was assessed as generally low. No trial had diagnosis of viral myocarditis confirmed histologically, and few trials attempted to establish viral aetiology for the myocarditis. Twenty-five different herbal medicines were tested in the included trials, which compared herbs with supportive therapy (17 trials), other controls (three trials), or treatment of herbs plus supportive therapy with supportive therapy alone (20 trials). The trials reported electrocardiogram, myocardial enzymes, cardiac function, symptoms, and adverse effects. Astragalus membranaceus (either as single herb or compound of herbs) showed significantly effects on improving arrhythmia, CPK levels, and cardiac function. Salviae miltiorrhizae injection showed significant effects on decreasing the arrhythmia and reducing LDH levels. Shenmai and Shengmai injection (Ginseng preparation) showed significantly effects on reducing myocardial enzymes and improving cardiac function. No serious adverse effect was reported.

CONCLUSIONS

Some herbal medicines may have anti-arrhythmia effect in suspected viral myocarditis. However, interpretation of these findings should be careful due to the low methodological quality, small sample size, and limited number of trials on individual herbs. In the light of the findings, some herbal medicines deserve further examination in rigorous trials.

The changes in calycosin and calycosin-7-O-beta-D-glucoside content as well as the expression of genes involved in their biosynthesis were monitored in roots, stems and leaves of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao seedlings during 10 days of low temperature treatment. The concentrations of calycosin and its 7-O-beta-D-glucoside in the different tissues were analyzed using high-performance liquid chromatography. Higher glycoside contents were observed at 2 degrees C than that at 16 degrees C in all the tested tissues, however, the aglycone was scarcely detected in both leaves and stems at either 16 or 2 degrees C. cDNA fragments encoding four structural genes from the calycosin pathway, namely chalcone synthase, isoflavone synthase, isoflavone 3'-hydroxylase and UDP-glucose: calycosin-7-O-glucosyltransferase were isolated from A. membranaceus var. mongholicus seedlings by polymerase chain reaction (PCR) and sequenced. Real-time quantitative reverse transcript PCR demonstrated that in leaves and stems, five genes (including phenylalanine ammonia lyase), exhibited clear differences in their accumulation pattern in response to a low temperature stress, which was consistent with the increased content of calycosin-7-O-beta-D-glucoside. In the roots, transcription of the five genes was down-regulated at 2 degrees C, but the contents of calycosin and its glucosides were higher than that at 16 degrees C. These findings indicate that low temperature stress could induce accumulation of calycosin and its glucosides in different tissues of the seedlings of A. membranaceus var. mongholicus but the mechanisms regulating the accumulation were different.

Chemoresistance is a major obstacle to successful chemotherapy for glioma. Formononetin is a novel herbal isoflavonoid isolated from Astragalus membranaceus and possesses antitumorigenic properties. In the present study, we investigated the anti-proliferative effects of formononetin on human glioma cells, and further elucidated the molecular mechanism underlying the anti-tumor property. We found that formononetin enhanced doxorubicin cytotoxicity in glioma cells. Combined treatment with formononetin reversed the doxorubicin-induced epithelial-mesenchymal transition (EMT) in tumor cells. Moreover, we found that formononetin treatment significantly decreased the expression of HDAC5. Overexpression of HDAC5 diminished the suppressive effects of formononetin on glioma cell viability. Furthermore, knockdown of HDAC5 by siRNA inhibited the doxorubicin-induced EMT in glioma cells. Taken together, these results demonstrated that formononetin-combined therapy may enhance the therapeutic efficacy of doxorubicin in glioma cells by preventing EMT through inhibition of HDAC5.

BACKGROUND

Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao (A. mongolicus) is an important traditional Chinese herb that is cultivated on a large scale in northwestern China. Understanding plant responses to drought has important effects on ecological environment recovery and local economic development. Here, we combined transcriptomics (Illumina Hiseq 2000) and metabolomics ((1)H-NMR) to investigate how the roots of two-year-old A. mongolicus responded to 14 days of progressive drought stress.

RESULTS

The dried soil reduced the relative water content (RWC) of the leaves and biomass, induced the differential expression of a large fraction of the transcriptome and significantly altered the metabolic processes. PCA analysis demonstrated that the sucrose, proline, and malate metabolites contributed greatly to the separation. Strikingly, proline was increased by almost 60-fold under severe stress compared to the control. Some backbone pathways, including glycolysis, tricarboxylic acid (TCA) cycle, glutamate-mediated proline biosynthesis, aspartate family metabolism and starch and sucrose metabolism, were significantly affected by drought. An integrated analysis of the interaction between key genes and the altered metabolites involved in these pathways was performed.

CONCLUSIONS

Our findings demonstrated that the expression of drought-responsive genes showed a strong stress-dose dependency. Analysis of backbone pathways of the transcriptome and metabolome revealed specific genotypic responses to different levels of drought. The variation in molecular strategies to the drought may play an important role in how A. mongolicus and other legume crops adapt to drought stress.

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. This study was carried out to investigate the effects of PAE on liver fibrosis induced by porcine serum (PS) in rats and to explore its possible mechanisms. Liver fibrosis was induced in male Wistar rats by injection with PS intraperitoneally. The rats were randomly divided into a normal control group, a liver fibrosis model group and a PAE (40, 80, 160 mg•kg-1) treated group. After a 16-week treatment, PAE-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis upon pathological examination. Administration of PAE significantly decreased serum HA, PC III levels, and content of hydroxyproline in the liver tissue of fibrotic rats. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during PS treatment. In vitro, PAE also significantly decreased [3H]-thymidine incorporation in hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB). Moreover, PAE significantly decreased the expression of PDGF receptor beta (PDGFR-β) and p-ERK1/2, p-p38, p-JNK. The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of liver fibrosis.

Astragaloside IV (ASI), a traditional Chinese medicine, is a main active ingredient of Astragalus membranaceus. Many clinical studies have found that ASI protects cardiomyocytes in cardiovascular diseases, but the underlying mechanisms remain obscure. The aim of this study was to investigate the molecular mechanisms responsible for the protective effects of ASI in cardiomyocytes from anoxia/reoxygenation (A/R) injury. According to the previous studies, we hypothesized that the cardioprotective effects of ASI against A/R injury might be associated with Notch1/Hes1 signaling pathway. In this study, neonatal rat primary cardiomyocytes were preconditioned with ASI prior to A/R injury. Our results showed that ASI effectively increased the cell viability, decreased the content of MDA, decreased the activities of CPK and LDH, increased the activities of GSH-Px and SOD, and reduced the reactive oxygen species (ROS) generation and the loss of mitochondrial membrane potential (Δψm). ASI inhibited the mitochondrial permeability transition pore (mPTP) opening and activation of caspase-3, and finally decreased the cell apoptosis in cardiomyocytes. Furthermore, ASI upregulated Hes1 protein expression. However, pretreatment with DAPT, a Notch1 inhibitor, effectively attenuated the cardioprotective effects of ASI against A/R injury, except MDA, SOD, GSH-Px, and the ROS generation. Taken together, we demonstrated that ASI could protect against A/R injury via the Notch1/Hes1 signaling pathway.

Astragalosides were the main active components from a native Chinese herb Astragalus membranaceus. Recent studies have shown that Astragalosides have a protective effect on myocardial injury in rats. The present study was designed to investigate the effect of Astragalosides on intracellular calcium overload and sarcoplasmic reticulum calcium load (SR Ca2+ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 microg/ml) were incubated in the presence of isoproterenol (ISO) (10(-5) M) for 72 hours in cardiomyocytes. Metoprorol (10(-6) M), a beta1-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([Ca2+]i) and SR Ca2+ load increased in ISO-treated cardiac myocytes as compared to control (P < 0.01). Astragalosides prevented ISO-induced increase in [Ca2+]i and SR Ca2+ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca2+ ATPase (SERCA) were enhanced following ISO treatment in cardiac myocytes, and these increases were inhibited by Astragalosides or metoprolol (P < 0.05). The decrease of superoxide dismutase (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were observed after ISO treatment in cardiac myocytes. Both Astragalosides and metoprolol restored the SOD activity and reduced the level of MDA. We conclude that Astragalosides have the effects on reducing [Ca2+]i and SR Ca2+ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.

Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness, and airway remodelling. Astragaloside IV (3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosyl-cycloastragenol, AST), the primary pure saponin isolated from the root of Astragalus membranaceus, is an effective compound with distinct pharmacological effects including anti-inflammation, immunoregulation, and antifibrosis. However, the effect of AST on asthma remains unclear. In the present study, in the murine model of asthma, the airway hyperresponsiveness was relieved after treatment with AST, accompanied by a reduction of inflammatory cells. In addition, the levels of IL-4 and IL-5 decreased, while the IFN-γ level increased, in bronchoalveolar lavage fluid. The compound also significantly inhibited the synthesis of GATA-3-encoding mRNA and protein in addition to increasing the synthesis of T-bet-encoding mRNA and protein in both lung tissues and CD4+ T cells. Our findings indicate that AST treatment inhibits ovalbumin-induced airway inflammation by modulating the key master switches GATA-3 and T-bet, which results in committing T helper cells to a Th1 phenotype.

Astragaloside IV, a new cycloartane-type triterpene glycoside extract of Astragalus membranaceus Bunge, has been identified for its potent immunoregulatory, antiinflammatory, and antifibrotic actions. Here we investigated whether astragaloside IV could suppress the progression of airway inflammation, airway hyperresponsiveness, and airway remodeling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks. Astragaloside IV was orally administered at a dose of 50 mg x kg-1 x day-1 during each OVA challenge. Astragaloside IV treatment resulted in significant reduction of eosinophilic airway inflammation, airway hyperresponsiveness, interleukin (IL)-4 and IL-13 levels in bronchoalveolar lavage fluid, and total immunoglobulin E levels in serum. Furthermore, astragaloside IV treatment markedly inhibited airway remodeling, including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. In addition, the expression of transforming growth factor-beta1 in the lung was also reduced by astragaloside IV. These data indicate that astragaloside IV may mitigate the development of characteristic features in chronic experimental asthma.

OBJECTIVE

To observe the angiogenesis promoting effects of clinical common used Chinese herbal medicines (CHM) for activating blood circulation to remove stasis on chick embryo chorio-allantoic membrane (CAM).

METHODS

Chicken CAM model was established and mice blood serum containing different kinds of medicines, including Radix Peaoniae rubra, Radix Angelicae sinensis, Flos Carthami, Rhizoma Chuanxiong, Radix Salviae miltiorrhizae, Astragalus membranaceus, and their complex prescriptions, Danggui Buxue Decoction, Xuefu Zhuyu Decoction, Xiongshao Capsule, was applied on it respectively to observe the condition of angiogenesis 72 hrs after incubation. Besides, the normal saline group, blank serum group, blank group and basic fibroblast growth factor (bFGF) group were set up for control.

RESULTS

All the CHM applied and bFGF had the CAM angiogenetic promoting effect, among them, Radix Salviae Miltiorrhizae and the three complex prescriptions showed better effects than the three negative control groups in capillary formation and count, with the efficacy similar to that of bFGF. The effect of complex prescriptions was superior to that of single herb except Radix Salviae miltiorrhizae.

CONCLUSIONS

Radix Salviae miltiorrhizae, Danggui Buxue Decoction, Xuefu Zhuyu Decoction and Xiongshao Capsule have good angiogenesis promoting effect on CAM. This study elucidated, from a certain aspect, the mechanism of action of CHM on ischemic diseases, and unfolded the scientific evidence of applying complex prescription.

Astragaloside IV (AS-IV), the major active component extracted from Astragalus membranaceus, has been demonstrated to exhibit protective effects on the cardiovascular, immune, digestive and nervous systems; thus, has been widely used in traditional Chinese medicine. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with the initiation and progression of cardiovascular diseases, including atherosclerosis and restenosis. However, the effects of AS-IV on VSMCs remain unknown. For the first time, the present study demonstrated that AS-IV markedly suppressed platelet-derived growth factor (PDGF)-BB-stimulated cellular proliferation and migration of HDMEC-a human dermal VSMCs (HDVSMCs). Further investigation into the underlying molecular mechanisms demonstrated that the administration of AS-IV attenuated the PDGF-BB-stimulated switch of HDVSMCs into a proliferative phenotype. Furthermore, AS-IV inhibited the PDGF-BB-induced expression of cell cycle-associated proteins, as well as the upregulation of matrix metalloproteinase (MMP)2, but not MMP9. In addition, AS-IV was shown to downregulate the activation of p38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB in HDVSMCs. Therefore, the observations of the present study indicate that AS-IV inhibits PDGF-BB-stimulated VSMC proliferation and migration, possibly by inhibiting the activation of the p38 MAPK signaling pathway. Thus, AS-IV may be useful for the treatment of vascular diseases.

Osteoarthritis is a multifactorial disease characterized by loss of articular cartilage and subchondral plate thickening. Therefore, biochemical analysis of the underlying bone tissue has provided important information for treatment of osteoarthritis. In this study, we determined the potential role of formononetin, a phytoestrogen isolated from Astragalus membranaceus to alter the expression of metabolic markers and cytokine production of human normal osteoblasts (Obs) and osteoarthritis subchondral osteoblasts (OA Obs). Human OA Obs and normal Obs were cultured for 3days, 7days or 14days in the present medium only or were treated with various doses of formononetin. Cells were analyzed for viability by WST-8 assay, alkaline phosphatase (ALP) activity, osteogenic markers (osteocalcin (OCN) and type I collagen (Col I)) and cytokines (interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)). The level of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with normal Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and Col I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal Obs. Interestingly, formononetin markedly increased the expression of VEGF and BMP-2 for 3days of culture and significantly increased OCN and Col I at 14days in human normal Obs. The remodeling effect of formononetin on osteogenic markers and cytokines of inflammatory mediators was more striking in OA Obs as well. Taken together, these results could suggest that formononetin has biphasic positive effects on normal Obs and OA Obs by modifying their biological synthetic capacities.

Tumors are known to produce factors suppressing macrophage function. In this study we demonstrated in vitro suppression of macrophage chemiluminescent oxidative burst associated with viable cells and cell-free extracts of two urological neoplasms--murine renal cell carcinoma (Renca) and murine bladder tumor (MBT). Suppression was reversed by extracts of two Chinese medicinal herbs, Astragalus membranaceus (AM) and Ligustrum lucidum (LL). Murine macrophage cell line J774 was incubated with either the viable tumor cells or the cell-free tumor extract for 18 hours at 37C and 5% CO2. Chemiluminescent oxidative burst as an indicator of macrophage function was triggered by adding zymosan A suspension containing luminol and assayed in an automated luminometer. Photon emission over time was counted and the results were expressed as integrated photon emission. Significant dose-related depression of oxidative burst occurred with either the viable tumor cells or the cell-free tumor extracts. Depression was partially or completely reversed by the presence of 50-100 micrograms./ml. of either the AM or the LL extract. AM and LL have previously been shown to modulate immune response. Data from this study suggest that they may also exert their antitumor activity via abolition of tumor-associated macrophage suppression.

BACKGROUND

Astragalus membranaceus which was originally described in the Shennong's Classic of Materia Medica, the earliest complete Pharmacopoeia of China written from the Warring States Period to Han Dynasty, has been widely used in Chinese medicine for>> 2000 years, especially in the prescription of curing cancer. A. membranaceus has various bioactivities, such as anti-tumor, anti-viral, anti-oxidant, anti-diabetes, anti-inflammation, anti-atherosclerosis, immunomodulation, hepatoprotection, hematopoiesis, neuroprotection and so on. As an important component of A. membranaceus, whether formononetin has a close relationship with its tumor-inhibiting effect on ovarian cancer cell has been investigated.

OBJECTIVE

The present study aimed to demonstrate the anti-proliferation, anti- migration and invasion effects of formononetin on ovarian cancer cells and further explore the underlying molecular mechanisms associated with apoptosis, migration and invasion.

METHODS

MTT assay was performed to detect the viability of ovarian cancer cells. DAPI staining, Annexin-V assay and assay for mitochondrial membrane potential detected the apoptosis of ovarian cancer cells treated by formononetin. The migration and invasion of ovarian cancer cells which exposed to formononetin were detected by scratch assay and transwell assay. Meanwhile, the protein-level changes of in ovarian cancer cells treated by formononetin were assessed by western blot analysis.

RESULTS

MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with formononetin. DAPI staining, Annexin-V assay and assay for mitochondrial membrane potential suggested that formononetin suppressed cells proliferation by inducing apoptosis. We detected the expression of apoptosis-related proteins in ovarian cancer cells after treatment with formononetin and found the expression of caspase 3/9 proteins and the ratio of Bax/Bcl-2 were increased in a dose-dependent manner. In addition, wound healing and transwell chamber assays showed that formononetin suppressed the migration and invasion of ovarian cancer cells. And formononetin decreased expression of MMP-2/9 proteins and phosphorylation level of ERK.

CONCLUSIONS

The present results demonstrated that formononetin have potential effects on induction of apoptosis and suppression of migration and invasion.

OBJECTIVE

Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte.

METHODS

H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague-Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining.

RESULTS

We found that 10 μg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV.

CONCLUSIONS

AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.

Radix Astragali extract (RAE) is obtained from Astragalus membranaceus. It consists of Astragalus polysaccharide and Astragalus membranaceus saponins. In the study, we observed the subchronic toxicity of RAE in Sprague-Dawley rats and beagle dogs to evaluate the safety dosage range in clinical application. These subjects were daily administered of RAE by intra-peritoneum or vein for three consecutive months. General index were observed such as food-intake, behavior, body weight, hematological parameters, etc. Body weight, the weight of principal organ and hematology index are normal in experimental groups and control groups. The hematological biochemistry examination and histopathology examination of experimental groups are similar to control groups. In conclusion, our studies clearly demonstrated that RAE was safe without any distinct toxicity and side effects, the safety dosage range is 5.7-39.9g/kg for rats and 2.85-19.95g/kg for beagle dogs, which is equal to 70 or 35 times of that of human (0.57g/kg, say, average BW 70kg), respectively.

Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.

Astragalus membranaceus is an herbaceous perennial plant, growing to about 2 feet tall, with sprawling stems and alternate leaves about 12-24 leaflets. In total, 24 cross bred (Duroc × Landrace × Yorkshire) piglets weaned at 4 weeks with an average body weight of 10.84 ± 1.86 kg, were divided into four groups and randomly assigned to dietary treatments containing different AMSLF levels (0.00%, 2.50%, 5.00%, and 7.50%). The piglets in the control group (0.00% AMSLF) were fed basal diet and other treatment groups were fed basal diet in addition to 2.50%, 5.00%, and 7.50% pulverized AMSLF. The results indicated that supplementation with AMSLF significantly (p < 0.05) decreased diarrheal incidence in piglets. There was significant difference between treatment in terms of ADFI, ADG and FCR. Both 5.00% and 7.50% treatments significantly increased growth performance. The digestibility of gross energy and dry matter increased (p>> 0.05) with increasing AMSLF level. The level of blood IL-2 and TNF-α were significantly affected by AMSLF supplementation with 7.50% AMSLF group having higher (p < 0.05) IL-2 and TNF-α levels than the other treatment groups. The 16SrDNA sequencing results from the four treatments showed that the potentially active bacterial microbial population and diversity in pig cecum were dominated by the phyla Bacteriodetes and Firmicutes regardless of the AMSLF supplementation. The Shannon diversity, PD whole tree diversity indices and Chao analyses exhibited significant variability in species richness across the treatments. The principal coordinates analysis (PCoA) showed significant (p < 0.1) differences between bacterial communities in all treatment groups. Results from the current study suggested that AMSLF supplementation increased composition of bacterial microbiota in pig gut. In conclusion, dietary supplements with AMSLF could potentially be used to prevent diarrheal incidence and improved pig production.

Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study. Oral administration of AS-IV (10 and 20mg/kg, once per day, started 7days before surgery and continued for 7days after surgery) significantly attenuated memory impairment and neuroinflammation. Moreover, AS-IV treatment significantly reduced the expression of toll-like receptor-4 (TLR4) and its downstream adaptor proteins, including myeloid differentiation primary response gene 88 (MyD88), toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-β (TRIF) and tumour necrosis factor receptor associated factor-6 (TRAF6), and subsequently inhibited NF-κB phosphorylation. It is well-known that cerebral ischemia and reperfusion injury enhances the formation of reactive oxygen species (ROS) and further neuroinflammation. Importantly, we found that AS-IV suppressed NLRP3 inflammasome activation by controlling ROS production. In addition, AS-IV markedly reduced overactivation of microglia and the overexpression of inflammatory cytokines in the hippocampus compared with the transient cerebral ischemia and reperfusion group. These results suggest that AS-IV might possess neuroprotective effects against transient cerebral ischemia and reperfusion partly through its anti-inflammatory effects by inhibiting TLR4 signaling pathway and NLRP3 inflammasome overactivation.

Melanin is a normal production protecting skin from environment-causing damage. Plants produce some agents in response to their environment. These agents could be applied in cosmetic production. Some Chinese herbals have immunomodulatory activities and modulate the symptoms of several diseases. Melanogenesis represents a complex group of conditions that are thought to be mediated through a complex network of regulatory processes. Previously, some studies found that the extracts of Astragalus membranaceus (PG2) regulated immunity and supported hematopoiesis. Herein, we want to determine the molecular mechanisms by which PG2 inhibits melanogenesis in B16F10 melanoma cells. The cellular melanin contents and expression of melanogenesis-related protein, including microphthalmia associated transcription factor (MITF) and tyrosinase were significantly reduced after PG2 treatment. Moreover, PG2 increased phosphorylation of ERK, without affecting phosphorylation of p38. These results suggested that PG2 as a new target in reducing hyperpigmentation through the ERK signal pathway. PG2 has potential for cosmetic usage in the future.

Astragaloside IV (AS-IV) is an active ingredient in Astragalus membranaceus, and involved in various biological processes, such as regulating the immune system, and counteracting inflammation and malignancy. The aim of this study was to explore the effect of AS-IV on non-small cell lung cancer (NSCLC) cells. A cell counting kit (CCK)-8 assay and flow cytometry were performed to investigate cell survival and cell death, and Western blotting was performed to assess protein expression. We found that AS-IV inhibited the migration and proliferation of NSCLC cells, and caused a noticeable increase in cell death. Furthermore, the expression of Bax, a marker of cell death, was increased, while the expression of Bcl-2, an anti-apoptotic protein, was reduced. AS-IV also promoted cleavage of caspase-3, another indication of apoptosis. Finally, the Akt/GSK-3β/β-catenin axis was suppressed in response to AS-IV. Taken together, these findings provide evidence that AS-IV inhibits NSCLC development via inhibition of the Akt/GSK-3β/β-catenin signaling axis. We therefore propose that AS-IV represents a promising novel agent for the treatment of NSCLC.