We tested the effect of Astragalus membranaceus (AM) on acute hemorrhagic stroke. Seventy-eight patients were randomly assigned to Group A (3 g of AM three times/day for 14 days); or Group B (3 g of placebo herb). A total of 68 patients (Group A 36, Group B 32) completed the trial. The increase of functional independence measure scale score between baseline and week 4 was 24.53 ± 23.40, and between baseline and week 12 was 34.69 ± 28.89, in the Group A was greater than 11.97 ± 11.48 and 23.94 ± 14.8 in the Group B (both P≦0.05). The increase of Glasgow outcome scale score between baseline and week 12 was 0.75 ± 0.77 in the Group A was greater than 0.41 ± 0.50 in the Group B (P < 0.05). The results are preliminary and need a larger study to assess the efficacy of AM after stroke.

OBJECTIVE

To explore the effects of large dose of Astragalus membranaceus (Astragalus) on the dentritic cell (DC) induction in vitro and augumentation by peripheral mononuclear cell (MNC) and on antigen presenting ability of DC in children with acute leukemia.

METHODS

Forty-four children with acute leukemia in complete remission stage were divided into two groups. Twenty patients in the Astragalus (90 g daily) group were treated with large dose of Astragalus (90 g daily) based on conventional chemotherapy for one month, while 24 patients in the control group received chemotherapy alone. MNC were extracted from peripheral blood by wall-sticking method and cultured with such cell factors as interleukin-4, gramulocyte macrophage colony stimulating factor, tumor necrosis factor-alpha for 7-8 days. Phenotype of DC was assayed by flow cytometry and antigen presenting ability of them was assayed by mixed lymphocyte reaction.

RESULTS

There was no morphological difference in MNC induced DC between the two groups. The average number of DC in Astragalus group and control group was 4.4 x 10(6) / 2.5 x 10(6) MNC and 2.6 x 10(6) / 2.5 x 10(6) MNC, respectively, showing significant difference (P < 0.001). DC in Astragalus group could stimulate the proliferation of allogeneic lymphocytes strongly, showing significant difference when compared with that in the control group (P < 0.001). Conclusion Large dose of Astragalus could increase the DC induction of MNC and enhance the antigen presenting ability of DC in acute leukemia patients.

The inhibitory effects of astrapterocarpan, formononetin, and calycosin isolated from Astragalus membraneceus on platelet-derived growth factor (PDGF)-BB-induced proliferative response in rat vascular smooth muscle cells (A10 cells) were investigated. Astrapterocarpan significantly inhibited PDGF-BB-induced cell proliferation and DNA synthesis in a concentration-dependent manner. This inhibition was not attributed to toxicity. In contrast, formononetin and calycosin had no effect. We next examined the effect of astrapterocarpan on PDGF-BB signal transduction. Astrapterocarpan inhibited PDGF-BB-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERIC1/2) mitogen-activated protein (MAP) kinase. However, this compound had no effect on phosphorylation of PDGF-beta-receptor, Akt kinase and p38 MAP kinase. These results indicated that astrapterocarpan inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and that this effect may be mediated, at least in part, by inhibition of the ERK1/2 MAP kinase cascade.

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development (IC25 = 3.37 x 10(-5) mg/mL) less than 17beta-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3 +/- 4.2% and 138.5 +/- 10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.

The main pathological change of radiation-induced heart disease is fibrosis. Emerging evidence has indicated that Astragalus membranaceus and its extractant, Astragalus saponin (AST), were used for treating fibrosis diseases. In the present study, the effects of AST on fibrosis damage induced by irradiation were determined. After being irradiated with 1 or 2-Gy X-rays, obvious changes of endoplasmic reticulum morphology were observed in cardiac fibroblasts (CFs), suggesting that its protein processing function was imbalanced, which indirectly indicated that fibrosis damage was caused by irradiating CFs. The expression levels of TGF-β1 and collagen I (Col-1) were increased at 48-h post-irradiation. Administration of 20 μg/ml AST reduced the production of reactive oxygen species in irradiated CFs and decreased the expression of Col-1, TGF-β1, and p-Smad2/3. Polymerase chain reaction (PCR)-array analysis showed that there were ~30 genes which were mainly classified into extracellular matrix, remodeling enzymes, inflammatory cytokines/chemokines, and TGF-β superfamily, were up-regulated after treatment with 1-Gy X-ray, whereas most of these genes were down-regulated when pretreated with 20 μg/ml of AST. In addition, TIMP1 and Smad7 genes that were down-regulated after treatment with 1-Gy X-ray were up-regulated when pretreated with 20 μg/ml of AST. In conclusion, radiation-induced fibrosis damage was observed at a cellular level. AST attenuated this fibrosis damage effect in irradiated CFs and this anti-fibrosis effect may be closely related to its antioxidant action. The involvement of fibrosis-related molecules in irradiated CFs was systematically demonstrated by a PCR array for the first time. AST reversed the expression of the majority of genes changed by irradiation, which further confirmed its anti-fibrosis effect.

OBJECTIVE

To observe the influence of Salvia miltiorrhiza (SM) and Astragalus membranaceus (AM) on hemodynamics and liver fibrosis indexes in patients of liver cirrhosis with portal hypertension.

METHODS

Eighty-four cases of liver cirrhosis were enrolled and divided randomly into two groups, 42 in each. The control group was treated with conventional therapy and the tested group treated with SM and AM. The parameters, including diameter of portal vein and splenic vein (Dpv and Dsv), speed of blood flow in portal vein and splenic vein (Spv and Ssv), quantity of blood flow in portal vein and splenic vein (Qpv and Qsv) as well as liver fibrosis indexes, such as HA, PC III and LN, were determined before, 1, 2 and 3 months after treatment.

RESULTS

After treatment, in the tested group, Dpv and Dsv decreased, Spv and Ssv increased, and Qpv and Qsv reduced, showing a significant difference in comparison with those in the control group (P < 0.05 or P < 0.01). The liver fibrosis indexes were improved significantly in the tested group, also showed significant difference from those in the control group (P < 0.01).

CONCLUSIONS

SM and AM could improve portal hypertension effectively in liver cirrhosis patients, one of the mechanism may be related with the improvement of liver fibrosis.

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations.

Astragalus polysaccharides (APS), one of the major active components in Astragalus membranaceus, is an effective immunomodulator used in the treatment of immunological diseases in China. However, the anti-infective action and mechanism of APS is not fully known. In the present study, we found that APS induced the expression of human cathelicidin antimicrobial peptide LL-37, a key host anti-infective molecule, in both mRNA and protein levels in respiratory epithelial cells HBE16 and A549. Furthermore, the lysate and supernatant from APS-treated HBE16 cells both exhibited an obvious antibacterial action, which was partially neutralizated by LL-37 monoclonal antibody. In addition, APS also significantly elevated the phosphorylation of p38 MAPK and JNK and caused the degradation of IκBα. Specific inhibitors of p38 MAPK, JNK, or NF-κB obviously abolished APS-induced LL-37 synthesis and antibacterial activity, respectively. Taken together, our results confirmed the enhancement of APS on LL-37 induction and antibacterial action in respiratory epithelial cells, which may be attributed to activation of p38 MAPK/JNK and NF-κB pathways. Furthermore, these results also supported the clinical application of APS in the treatment of infectious diseases.

Astragalus membranaceus and Salvia miltiorrhiza (AM/SM) are well used in Traditional Chinese Medicines (TCM) for nourishing Qi and activating blood circulation method. From TCM theory, the pathogenesis of acute lung injury (ALI) was determined as Qi deficiency and blood stagnation. In this study, we are aiming to investigate the protective and therapeutic effects of AM/SM on a rat model of lipopolysaccharide- (LPS-) induced ALI in rats and to elucidate potential molecular mechanisms. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in Sprague-Dawley rats. SM/AM was given orally before and after LPS administration. Results demonstrated that AM/SM attenuated lung histopathological changes induced by LPS, decreased wet/dry weight ratios and protein concentrations, and inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in BALF. Moreover, AM/SM significantly downregulated protein and mRNA expression of toll-like receptors 4 (TLR-4), interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear factor-kappa B (NF-κB/p65). These findings suggest that AM/SM showed protective and therapeutic effects in LPS-induced ALI rat through modulating TLR-4 signaling pathways. Nourishing Qi and activating blood circulation may be a beneficial treatment for ALI.

To investigate the combination therapy of Western and traditional Chinese medicine on treatment of acute viral myocarditis, 48 patients were randomly divided into 2 groups. The 1st group consisted of 30 patients, receiving the combination therapy of Western and traditional Chinese medicine, including Astragalus membranaceus, taurine, coenzyme Q10 and antiarrhythmics, while the 2nd group consisted of 18 patients, receiving the conventional therapy, including glucose-insulin-potassium (GIK), coenzyme Q10 and also antiarrhythmics.

RESULTS

The efficacy of combination therapy of western and traditional Chinese medicine was better than that of conventional therapy in improving the clinical manifestation, negative converting positive EVsRNA in peripheral leukocytes and controlling the premature beats.

CONCLUSIONS

The combination therapy of western and traditional Chinese medicine was an effective method in treating acute viral myocarditis.

Astragaloside IV (AS-IV), a main active constituent of Astragalus membranaceus, has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS-IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS-IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL-4, IL-5, IL-13, IL-17, and INF-γ), and CD4+CD25+Foxp3+Treg cells in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling were examined. AS-IV markedly suppressed airway hyperresponsiveness and reduced IL-4, IL-5, and IL-17 levels and increased INF-γ levels in the BALF. Histological studies showed that AS-IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS-IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4+CD25+Foxp3+Treg cells in BALF were not significantly changed by AS-IV. Together, these results suggest that the antiasthmatic effects of AS-IV were at least partially from inhibiting the mTORC1 signaling pathway.

This study describes the screening of extracts obtained from 18 plants and two fungi used in the Chinese and Mediterranean traditional medicines on epimastigote forms of Trypanosoma cruzi. The extracts were tested against epimastigote of T. cruzi Bra C15C2 clone in vitro at 27 degrees C and at a concentration of 250 microg/ml in axenic culture. Angelica dahurica, A. pubescens, A. sinensis, Astragalus membranaceus, Coptis chinensis, Haplophyllum hispanicum, Phellodendron amurense, Poria cocos, Ranunculus sceleratus and Scutellaria baicalensis showed significant effects against the parasite with a percentage of growth inhibition between 20 and 100%. C. chinensis and R. sceleratus showed the greatest activity with IC(50) values of 1.7 microg/ml for C. chinensis and 10.7 microg/ml for R. sceleratus. These activities are greater than that of allopurinol. C. chinesis and R. sceleratus extracts did not show cytotoxic effects on rat polimorphonuclear cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactic dehydrogenase assays. These results allowed us to suggest that R. sceleratus and C. chinensis could be a source of new compounds clinically active against T. cruzi.

Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of β-catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/β-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/β-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/β-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/β-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/β-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright © 2016 John Wiley & Sons, Ltd.

Chinese herbal medicines (CHMs) containing aristolochic acid (AA) are associated with chronic kidney disease (CKD), but some prescribed CHMs have been shown to possess renoprotective effects. We conducted a nationwide retrospective cohort study to delineate the role of prescribed CHMs on the CKD progression. Renoprotective CHM (RPCHM) was defined if a CHM contained dong chong xia cao (Cordyceps sinensis (Berk.) Sacc.), da huang (Rheum palmatum L), huang qi (Astragalus membranaceus), dan shen (Salvia miltiorrhiza Bge.), and dong quai (Angelica sinensis (Oliv.) Diels) or belonged to specific mixture herbal formulations (Yishen capsule, Saireito, or Wen Pi Tang). Subjects who had ever used AA-containing CHMs, had cancer or HIV prior to CKD diagnosis, or died within the first month of CKD diagnosis were excluded. A total of 11,625 patients were eligible subjects. The adjusted hazard ratio (aHR) for all-cause mortality was 0.6 (p < 0.001) and 0.6 (p = 0.013) among subjects receiving RPCHMs containing Angelica sinensis and those receiving other RPCHMs, respectively. For CKD-related mortality, the aHR among subjects receiving RPCHMs containing Angelica sinensis was 0.6 (p = 0.025). The use of specific RPCHMs, especially those that contained Angelica sinensis, was associated with a lower risk of mortality among CKD patients.

Natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from 28 patients with systemic lupus erythematosus (SLE) was measured using enzyme-release assay. The SLE patients had significantly decreased NK activity in comparing with normal controls. The levels of NK activity correlated with disease activity. Pre-incubation of PBMC separately with Astragalus membranaceus and Tripterygium hypoglaucum or with their mixture considerably stimulated NK cytotoxicity both in SLE patients and healthy donors. The extent of enhancement was dose-dependent and relevant to pre-incubation periods. The release of a soluble natural killer cytotoxic factor (NKCF) by peripheral blood mononuclear cells was tested by cytotoxicity assay induced in K562 cells. Natural killer cytotoxic factor release was significantly lower in SLE patients than in controls. The levels of natural killer cytotoxic factor were correlated well with NK activities, but correlated negatively with clinical activity. Pre-incubated supernatants from peripheral blood mononuclear cells with above-mentioned agents caused much higher percentage of lysis on K562 targets than that of without pre-incubation.

OBJECTIVE

To explore the effects and mechanisms of combining astragaloside IV (the effective component of Astragalus membranaceus) with notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1 (the effective components of Panax notoginseng) against oxidative injury in PC12 cells induced by cobalt chloride (CoCl₂).

METHODS

CoCl₂ was used to stimulate PC12 cells to induce injury after transdifferentiation with nerve growth factor. Then the PC12 cells were divided into 10 groups and cultured with corresponding drugs. After culture, apoptotic cells were tested by using Hocchst 33258 fluorescent staining, the level of mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 fluorescent staining and the content of reactive oxygen species (ROS) in PC12 cell was measured by dichlorofluorescin diacetate fluorescent staining.

RESULTS

CoCl₂ induced apoptosis along with the obvious decrease of MMP as well as overproduction of ROS in PC12 cells. Astragaloside IV, ginsenosides Rg1, ginsenosides Rb1 and notoginsenoside R1 had inhibition effects in different degree on PC12 cell apoptosis induced by CoCl₂, reduced the overproduction of ROS and the decrease of MMP. The effects of the combination were better than those of active component alone.

CONCLUSIONS

Active components extracted from Astragalus and Panax notoginseng can inhibit PC12 cell apoptosis induced by oxidative injury, furthermore, the effects were enhanced by combination of these components, which may be associated with jointly antagonizing the generation of ROS and raising MMP.

The effect of HT042, a blend of three herbal extracts, on longitudinal bone growth was investigated in short- and long-term rat models. In the short-term model, we divided female Sprague-Dawley rats (3 weeks old) into six groups, according to treatment: vehicle, HT042 (100 mg/kg), Phlomis umbrosa (100 mg/kg), Astragalus membranaceus (100 mg/kg), and Eleutherococcus senticosus (100 mg/kg) were administered twice daily, and recombinant human growth hormone (rhGH) (1 IU) was subcutaneously injected once daily. Treatments were maintained for 4 days in each case. On day 3, tetracycline (20 mg/kg) was injected intraperitoneally (20 mg/kg) to form the fluorescent band on the growth plates. On days 2-4, 5-bromo-2'-deoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally to label proliferating cells. On day 5, the tibias were dissected and fixed in 30% sucrose. Dehydrated bone was sectioned at a thickness of 40 μm and observed. The bone growth in groups administered HT042 and rhGH was significantly increased to 433.50 ± 21.61 and 434.49 ± 15.21 μm/day, respectively, from 410.03 ± 17.4 μm/day (control). The height of the growth plates in the HT042 and rhGH groups was also significantly increased to 556.5 ± 21.1 and 544.2 ± 21.1 μm (P < .05), respectively, from 518.1 ± 4.1 μm (normal). The number of BrdU-positive cells in chondrocytes of the HT042 and rhGH groups was increased to 389 ± 36 and 627 ± 39 cells/mm² (P < .001), respectively, from 264 ± 17 cells/mm² (control). Insulin-like growth factor-1 and bone morphogenetic protein-2 in the HT042 group were highly expressed in the growth plate. In the long-term rat model, the body weight, nose-tail length, and nose-anus length were measured by microknemometry for 4 weeks. The body weight of the rhGH group was significantly increased. The nose-anus length of the HT042 and rhGH groups was significantly greater at 18.5 ± 0.3 and 18.7 ± 0.3 cm compared to 18.2 ± 0.2 cm (control).

Astragaloside IV (AS-IV) is a flavonoid from the plant Astragalus membranaceus (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present study was to examine the effect of AS-IV on rats with necrotizing enterocolitis (NEC) under oxidative stress and inflammation. Newborn Sprague-Dawley rats were induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The rats were orally administered AS-IV at 25, 50 and 75 mg/kg for 4 days. The results revealed that AS-IV administration prevented NEC-induced decrease in the concentration of malondialdehyde and myeloperoxidase, and increase in the activity of glutathione (GSH) and superoxide dismutase in murine models. AS-IV also inhibited NEC-induced elevation in the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α and nuclear factor (NF)-κB. The effects of AS-IV were achieved under inflammation and oxidative stress. Western blotting demonstrated that AS-IV substantially inhibited the phosphorylated (p)-IκBα, NF-κBp65, p-NF-κBp65 protein levels and increased vitamin D3 upregulated protein 1 (VDUP1) and IκBα protein levels. These data indicate that AS-IV may be effective in the protection of NEC-induced ileum degeneration by inhibiting the levels of inflammatory markers and oxidative stress via the regulation of the VDUP1/NF-κB signaling pathway.

OBJECTIVE

Astragalus membranaceus (AM) is the first-choice herb for fatigue treatment in traditional Chinese medicine and the main herb used for stroke treatment in China and Taiwan. The purpose of this study was to evaluate the effect of AM on poststroke fatigue (PSF).

METHODS

This study was designed as a double-blind, randomized, controlled preliminary study. Sixty-four patients with PSF were assigned to treatment group (TG; 31 patients), which received oral administration of AM (2.8g three times per day) for 28 days, and a control group (CG; 33 patients), which received a placebo. The primary outcome measures were the changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Brief Fatigue Index (BFI) scores RESULTS: A total of 61 patients (29 patients in the TG and 32 patients in the CG) completed the trial. The difference in BFI scores between Visit 2 and Visit 1 was -17.83±17.70 in the TG, which was greater than that in the CG (-8.03±9.95; p=0.01); additionally, the difference in BFI scores between Visit 3 and Visit 1 was -16.48±16.41 in the TG, which was also greater than that in the CG (-9.47±13.39; p=0.05). In the EORTC QLQ-C30, the difference in cognitive functioning scores between Visit 2 and Visit 1 was 14.37±13.89 in the TG, which was greater than that in the CG (3.65±19.74; p=0.02); additionally, the difference in these scores between Visit 3 and Visit 1 was 14.37±16.50 in the TG, which again was greater than that in the CG (6.25±19.74; p=0.04). The difference in social functioning scores between Visit 3 and Visit 1 was 9.77±15.12 in the TG, which was greater than that in the CG (-1.56±20.46; p=0.01). The difference in global quality of life (QOL) scores between Visit 2 and Visit 1 was 14.08±18.78 in the TG, which was also greater than that in the CG (1.56±18.14; p=0.003); moreover, the difference in these scores between Visit 3 and Visit 1 was 10.92±17.55 in the TG, and this was greater than that in the CG (1.82±15.8; p=0.05).

CONCLUSIONS

AM can improve BFI scores; cognitive functioning, social functioning, and global QOL scores in the EORTC QLQ-C30. Our results suggest that physicians should pay close attention to the unmet medical needs of patients with PSF. AM is helpful for treating patients with PSF; however, additional studies with a larger sample and a longer period of investigation are required.

We have investigated whether the saponin astragaloside IV (AS-IV), a 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol, purified from the Chinese herb drug Astragalus membranaceus, which is used in traditional Chinese medicine to treat cardiovascular diseases, might affect the fibrinolytic potential of cultured human umbilical vein endothelial cells (HUVECs). When HUVECs were conditioned with AS-IV, a dose (0.01-100 microg AS-IV/ml)- and time-dependent decrease in plasminogen activator inhibitor type 1 (PAI-1) and an increase in tissue-type plasminogen activator (t-PA) synthesis were observed, which were significant from 1 microg AS-IV/ml and from 12 h of incubation with 100 microg AS-IV/ml. PAI-1 antigen decreased from 641 +/- 86 to 318 +/- 18 ng/10(5) cells/24 h, whereas t-PA antigen increased from 4.1 +/- 0.3 to 9.7 +/- 0.4 ng/10(5) cells/24 h after addition of 100 microg AS-IV/ml. PAI-1 activity decreased to 30% of control level, whereas t-PA activity and t-PA-PAI-1 complexes reached a maximum stimulation of 3- and 5-fold over control levels, respectively, in the conditioned media of HUVECs treated with 100 microg AS-IV/ml for 24 h. PAI-1-specific mRNA expression decreased to 55% (2.2 kb) and 72% (3.2 kb), 66% (2.2 kb) and 88% (3.2 kb), and 19% (2.2 kb) and 41% (3.2 kb) of control values after incubation for 6, 12 and 18 h, respectively, whereas t-PA-specific mRNA increased 2-, 2.5- and 1.4-fold in HUVECs treated with 100 microg/ml AS-IV for 6, 12, and 18 h, respectively. In conclusion our data give evidence that in fact AS-IV can increase the fibrinolytic potential of cultured HUVECs not only by upregulating the expression of t-PA as NG-R1 does, but also by downregulating the expression of PAI-1.

Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl₄. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl₄-treated rats. Compared to rats treated with CCl₄ alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.

Ten constituents have been isolated from the alcoholic extract of Astragalus membranaceus var. monghlicum root. All of them were identified. Among them astraisoflavanin (3S-(-)-mucronulatol-7-O-D-glucopyranoside) is a new compound. Dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphyenyl 1-2, 2'-dicarboxylate is a known synthetic compound, but it was first isolated from natural resource Astragalus root and identified by the authors.

BACKGROUND

Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging.

RESULTS

AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure.

CONCLUSIONS

Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.

A reverse-phase high-performance liquid chromatographic method is developed for the determination of astragaloside IV, a characteristic constituent in Radix Astragali. Samples are analyzed by means of a reverse-phase column (Zorbax Eclipse XDB C18) using acetonitrile and water under gradient conditions as the mobile phase for 30 min. An evaporative light-scattering detector is used and set at an evaporating temperature of 43 degrees C with a nebulizing gas (compressed air) pressure of 3.4 bar. The detection limit (signal-to-noise ratio>> 5) of astragaloside IV is 40 ng on-column.