Total Flavonoids Of Astragalus Research Articles

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease

BackgroundDiabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear.MethodsIn this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods.ResultsOur findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress.ConclusionOur findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Network Pharmacology and Experimental Analyses on Astragalus membranaceus (Huangqi) Effects on Endotoxin-induced Uveitis Model in Rats

Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the Traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com ). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat’s iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

Effects of Taraxacum and Astragalus extracts combined with probiotic Bacillus subtilis and Lactobacillus on Escherichia coli–infected broiler chickens

Diarrhea caused by Escherichia coli (E. coli) is one of the most common diseases that affects the growth and development of poultry. This study was conducted to investigate the synergistic effects of traditional Chinese medicine (TCM) combined with probiotics against E. coli infection and its mechanism in broiler chickens. The optimal proportion formula TCM and probiotics was screened by orthogonal test and range analysis method; the in vitro antibacterial activity was based on the Oxford cup method. Isolated pathogenic E. coli was injected subcutaneously into the neck of the broilers to establish an E. coli–infected model. The broilers were administrated with drugs in drinking water daily for 7 d before and after E. coli infection. The diarrhea rate, mortality, body weight (BW) gain, feed intake, immune organ index, intestinal and hepatic histopathological changes were monitored. The expression of IL-2, IL-10, and TLR-4 mRNA in the intestinal tissues was measured by RT-PCR. Our results showed that the optimal proportion formula of Taraxacum extracts: total flavonoids of Astragalus: polysaccharides of Astragalus: probiotics was 5: 2: 2: 2; TCM combined with probiotics was highly sensitive to E. coli. TCM combined with probiotics synergistically increased BW gain, decreased the diarrhea rate and mortality of broilers, alleviated intestinal and hepatic pathological changes, accompanied by the increase of IL-2 and IL-10 mRNA expression and the inhibition of TLR-4 mRNA expression. It suggests that the combination of TCM and probiotics may produce a synergistic protective effect against E. coli infection by improving the indicators of diarrhea and regulating the expression of IL-2, IL-10, and TLR-4 mRNA in broiler chickens. The synergistic interactions between TCM and probiotics represent a promising strategy for the treatment of E. coli infection.

Total flavonoids of astragalus attenuates experimental autoimmune encephalomyelitis by suppressing the activation and inflammatory responses of microglia via JNK/AKT/NFκB signaling pathway

BackgroundMicroglia-mediated neuroinflammation is one of the most prominent characteristics of multiple sclerosis (MS), a chronic demyelination disease. As one of the main active ingredients in Astragali radix, total flavonoids of Astragalus (TFA) has multiple pharmacological effects such as immunomodulation, anti-inflammation and and anti-tumor. However, little is known about whether TFA could inhibit microglia-mediated neuroinflammation in MS. PurposeThis study was aimed to elucidate whether TFA could inhibit microglia-mediated neuroinflammation in MS. Study designIn the present study, we explored the protective effect of TFA on experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in mice for the first time, and discussed its mechanism from the aspect of anti-microglia-mediated neuroinflammation. MethodsThe mice received oral administration of TFA (25 and 50 mg/kg) daily from two days before immunization and continued until day 21 post-immunization. The effect of TFA on EAE in mice and its mechanism were investigated by ELISA, Western blot, real-time PCR, luciferase reporter assay, histopathology and immunohistochemistry. ResultsTFA were shown to alleviate the severity of EAE in mice. It inhibited the excessive activation of microglia both in spinal cords of EAE mice and in LPS-stimulated BV-2 cells, evidenced by weakening the production of inflammatory mediators such as NO, TNF-α, IL-6, and IL-1β markedly at either protein or mRNA level. Further study demonstrated that TFA repressed the phosphorylation, nuclear translocation and transcriptional activity of NFκB, and inhibited the activation of AKT and JNK signaling in BV-2 cells induced by LPS. The agonists of AKT and JNK, anisomycin and SC79, could partly abolish the inhibitory effect of TFA on the production of inflammatory mediators in BV-2 cells induced by LPS. ConclusionsTaken together, our results clarified that TFA inhibited microglia-mediated inflammation in EAE mice probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings may lay a theoretical foundation for the clinical application of TFA in the treatment of MS.

PSIV-B-40 Late-Breaking: Effects of Total Flavonoids of Astragaluson on Development, ROS Level and Antioxidant Enzyme Genes Expression in Oxidative Damage Mouse Embryos

Abstract In this study, the effect of total flavonoids of astragalus (TFA) on the development, ROS level and the expression of antioxidant enzyme genes in Kunming mouse during in-vitro culture. In the first experiment, effect of different concentration (0 mg/L, 25 mg/L, 50 mg/L, 75 mg/L and 100 mg/L) of TFA was used to determine optimal dose rate. In subsequent experiments, embryos were divided into three groups control, H2O2 treated and optimal concentration TFA+H2O2 treated groups. Our result shows that the 4th cell and blastocyst rate was significantly higher in 75 mg/L TFA group (P < 0.05) than the other groups. The intracellular ROS level was significantly higher in H2O2 group (P < 0.05) which was significantly decrease after the supplementation of TFA. Moreover the mRNA expression level of SOD1 and SOD2 in the TFA+H2O2 group were significantly higher than the H2O2 group (P < 0.05); however, the mRNA expression level of CAT, GPx1 and GPx4 were significantly higher in TFA+H2O2 group compared to H2O2 group (P < 0.01). In conclusion, the present shows that the optimal dose rate of TFA in vitro embryo culture was 75 mg/L. TFA treatment can reduce ROS level, improve the expression levels of CAT, SOD1, SOD2, GPx1 and GPx4 in blastocyst of mice in oxidative stress condition

Protective effects of total flavonoids of Astragalus against adjuvant-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway

BackgroundAstragalus membranaceus Bunge is one of the oldest and most frequently used crude herbs in traditional Chinese medicine. The total flavonoids of Astragalus (TFA) are the main active components isolated from Astragalus membranaceus Bunge. Our recent study has shown its potential immunomodulatory and anti-inflammatory effects in vivo and in vitro. However, its anti-arthritic effects and mechanisms of action involved have not been elucidated. The aim of this study was to evaluate the protective effects and possible mechanisms of TFA on Freund's complete adjuvant (FCA)-induced arthritis in rats. MethodsWistar rats were intradermally injected FCA into the right hind metatarsal footpads to establish adjuvant-arthritic model. The rats were intragastrically administered daily with TFA at 25, 50 and 100mg/kg for 28days after FCA induction. Body weight, primary paw swelling, arthritis index, thymus and spleen indices were measured. The levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, prostaglandin (PG)E2, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined using ELISA. Histopathological changes and scores in joint tissues were examined using hematoxylin and eosin (H&E). The expression of nuclear factor (NF)-κB p65 in synovial tissues was assayed using immunohistochemical method. ResultsTFA significantly increased body weight, attenuated primary paw swelling and arthritis index, decreased thymus and spleen indices of rats induced by FCA. Furthermore, TFA significantly inhibited serum TNF-α, IL-1β, PGE2 and RANKL production, and promoted serum OPG production and OPG/RANKL ratio of rats induced by FCA. Histopathological examination indicated that TFA significantly attenuated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone and cartilage damage. Immunohistochemical assay indicated that TFA inhibited NF-κB p65 expression in synovial tissues of rats induced by FCA. ConclusionsThese results suggest that TFA exerts potential protective effects against FCA-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway.

IN VIVO AND IN VITRO IMMUNOMODULATORY AND ANTI-INFLAMMATORY EFFECTS OF TOTAL FLAVONOIDS OF ASTRAGALUS.

Background:Astragali Radix has long been used to improve immune function in traditional Chinese medicine. However, its main active components and potential immunomodulatory or anti-inflammatory activities have not been elucidated. In the present study, the immunomodulatory and anti-inflammatory activities of total flavonoids of Astragalus (TFA) isolated from Astragali Radix were evaluated by using in vivo animal models and in vitro cell models.Materials and Methods:The in vivo Immunomodulatory and anti-inflammatory activities of TFA were assessed by measuring macrophage phagocytic index, delayed type hypersensitivity, serum hemolysin level and immune organ index in mice, ear edema test in mice, paw edema test in rats, vascular permeability test in mice and granuloma test in rats. The in vitro Immunomodulatory and anti-inflammatory activities of TFA were assessed by examining its effect on cytokine and mediator production in un-stimulated and LPS-stimulated murine RAW 264.7 macrophages.Results:The results of in vivo experiments showed that TFA enhanced macrophage phagocytic index, delayed type hypersensitivity, serum hemolysin level and immune organ index in mice, and attenuated mouse ear edema, rat paw edema, mouse vascular permeability and rat granuloma formation. The results of in vitro experiments showed that TFA stimulated the production of NO and cytokine TNF-α, IL-Ιβ, IL-6 and IFN-γ in un-stimulated RAW 264.7 macrophages, and inhibited the overproduction of these inflammatory mediators in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without exerting cytotoxicity.Conclusion:These results of this study indicate that TFA have potential immunostimulatory and anti-inflammatory effects.

Total Flavonoids of Astragalus Plays a Cardioprotective Role in Viral Myocarditis.

Viral myocarditis is initiated by viral infection of myocardial tissue leading to dilated cardiomyopathy and congestive heart failure. Recent studies have linked viral myocarditis with dysfunctions in endoplasmic reticulum (ER) mediated Ca(2+) homeostasis and the unfolded protein response (UPR). Currently there are no effective treatments for this viral infection. We employed the use of a well-characterized pathogen coxsackievirus B3 (CVB3) to induce mouse viral myocarditis. After intraperitoneal administration of total flavonoids of Astragalus (TFA), we examined the protective effect of TFA on CVB3-induced heart function impairment and decreased calumenin mRNA levels. Furthermore, calumenin protein level was studied in vivo and in vitro with CVB3 infection in the presence or absence of TFA. The interaction between calumenin and the sarco/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) was also tested in HL-1 cells. Whereas customarily we would expect that CVB3 infection would decrease mRNA and protein levels of the Ca(2+) binding ER chaperone calumenin, here TFA treatment prevented this decline in both CVB3 infected mice and in an in vitro system of infected HL-1 cardiomyocytes. CVB3 infection in HL-1 cells prevented the association of calumenin with the calcium mobilizing protein SERCA2, and TFA treatment rescued this interaction. This study identified that CVB3 infection promotes cardiomyocyte dysfunction by effecting expression levels and activity of the cardio protective ER chaperone calumenin. For the first time, TFA was shown to prevent loss of mRNA and protein levels of calumenin and also rescued the association of this protein with SERCA2. Calumenin; Sarco/endoplasmic reticulum Ca(2+)-ATPase; Total flavonoids of Astragalus; Viral myocarditis.

Study of the effects of total flavonoids of Astragalus on atherosclerosis formation and potential mechanisms.

Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.

Investigation of effects and mechanisms of total flavonoids of Astragalus and calycosin on human erythroleukemia cells.

Flavonoids are found in most parts of plants and have been shown to have multiple biological activities such as anticancer, anti-inflammation, antibacteria, antivirus, and immune-stimulation. Existing data showed that the total flavonoids of Astragalus (TFA) can provide biological system with resistance to injury and can possess antimutagenic, atherosclerotic inhibition, and other biological effects. This study investigated the effects of TFA and calycosin (a compound isolated from TFA), on apoptosis induction, and cell cycle of human erythroleukemia cell line K562 by an array of techniques, including proliferation (MTT), PI staining, Annexin V/PI double staining, and RT-PCR. The experimental data showed that TFA and calycosin could inhibit the proliferation of K562 cells. The 50% inhibiting concentrations of TFA and calycosin were 98.63 μg/mL and 130.32 μg/mL, respectively. However, TFA and calycosin could not induce apoptosis in K562 cells, but could increase the number of the cells in the G0/G1 phase. The level of cyclin D1 mRNA in K562 cells decreased after the treatment with TFA and calycosin. This study provides new insights into the functional mechanism of total flavonoids of Astragalus and calycosin on human erythroleukemia cells.

Progressive studies on biological activity of total flavonoids of Astragalus

Progresses in the studies on chemical constituents and bioactivities of total flavonoids of Astragalus (TFA) were systemically reviewed in this article. The results of studies on their bioactivities show that TFA has antioxidant and antitumor activities, and strengthen the immune system. Further biological studies on the species in total flavonoids of Astragalus are needed for better medicinal utilization.

Effect of total flavonoids of Astragalus on nitroxide in ischemia reperfusion injury

To study the protective effect of total flavonoids of Astragalus (TFA) on ischemia/reperfusion injury. Change of nitrite (NO2-), the terminal product of nitric oxide (NO) metabolism, and the effect of TFA and chloroquine (a phospholipase A2 inhibitor) on it were observed with hemorrhagic shock/reperfusion injury (S/R) rabbit model. Plasma NO2- content was positively correlated with blood pH and total carbon dioxide content lowering. TFA and chloroquine could block the decrease of NO in certain degree and might have some effect on maintaining acid-base balance of body. TFA has protective effect on ischemia/reperfusion injury.