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Atopic disease is a kind of abnormal immune reaction caused by tissue damage and physiological dysfunction caused by allergens. Atopic diseases involve many systems and have obvious genetic tendencies, threatening the quality of life, health, and life safety of human beings. Astragalus membranaceus is an ancient and commonly used traditional Chinese medicine widely used in allergic diseases. Astragaloside IV is one of the main active ingredients in Astragalus membranaceus and is an important index component for evaluating the quality of Astragalus membranaceus and Astragalus membranaceus preparations at present. It has good antiallergic and immunomodulatory effects. Therefore, this paper reviews and summarizes the mechanism of action, pharmacokinetics, and drug optimization research progress of astragaloside IV in the treatment of atopic diseases.

Descurainia sophia seeds (DS), Astragalus mongholicus (AM), and their formulas are widely used to treat heart failure caused by various cardiac diseases in traditional Chinese medicine practice. However, the molecular mechanism of action of DS and AM has not been completely understood. Herein, we first used mass spectrometry coupled to UPLC to characterize the chemical components of DS and AM decoctions, then applied MS-based quantitative proteomic analysis to profile protein expression in the heart of rats with isoproterenolinduced cardiomyopathy (ISO-iCM) before and after treated with DS alone or combined with AM, astragaloside IV (AS4), calycosin-7-glucoside (C7G), and Astragalus polysaccharides (APS) from AM. We demonstrated for the first time that DS decoction alone could reverse the most of differentially expressed proteins in the heart of the rats with ISO-iCM, including the commonly recognized biomarkers natriuretic peptides (NPPA) of cardiomyopathy and sarcomeric myosin light chain 4 (MYL4), relieving ISO-iCM in rats, but AM did not pronouncedly improve the pharmacological efficiency of DS. Significantly, we revealed that AS4 remarkably promoted the pharmacological potency of DS by complementarily reversing myosin motor MYH6/7, and further downregulating NPPA and MYL4. In contrast, APS reduced the efficiency of DS due to upregulating NPPA and MYL4. These findings not only provide novel insights to better understanding in the combination principle of traditional Chinese medicine but also highlight the power of mass spectrometric proteomics strategy combined with conventional pathological approaches for the traditional medicine research. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic retinopathy (DR) is a serious complication of diabetes mellitus, which nearly happens to all the diabetic sufferers. This study aims to identify the preliminary molecular regulation involved in the therapeutic efficacy of astragaloside IV (AS- IV) for DR. Methods: Diabetic rat models were established and treated with AS-IV. Optical coherence tomography (OCT) and Hematoxylin-eosin (HE) staining was employed to demonstrate the histopathological changes. The main targets of AS-IV were identified by searching from public databases of traditional Chinese medicine (GeneCards, PharmMapper and Swiss Target Prediction). Besides, disease targets of DR were also obtained by integrated data from GEO datasets and predicted from public databases. Protein-protein interaction (PPI) network was constructed by Cytoscape with overlapping genes and 10 core targets were selected, on which Gene Ontology (GO) along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. The interaction between AS-IV and these crucial genes were analyzed using molecular docking. RT-qPCR and western blot were used to verify the expression variation of core targets. Results: OCT imaging and HE staining demonstrated that AS-IV administration significantly increased retinal thickness in diabetic rats, obviously alleviating DR induced histopathological changes as well as elevated blood glucose levels. 107 common targets of AS-IV and DR were determined after intersection. PPI network analysis filtered 10 hub genes potentially targeted by AS-IV, including VEGFA, CASP3, HIF1α, STAT3, CTNNB1, SRC, AKT1, EGFR, IL1β and IL6. Enrichment analysis indicated that these genes were mainly enriched in biological processes like T cell activation, epithelial cell proliferation and protein kinase B signaling, and involved in oxidative stress, apoptosis and inflammation-related pathways. The molecular docking prediction suggested that AS-IV exhibited stable binding to these core targets. In addition, mRNA levels of core targets in diabetic rats were differentially expressed before and after AS-IV treatment. Western blot further revealed that AS-IV treatment elevated DR-depressed protein levels of PI3K and AKT. Conclusion: Our study elucidated the effect of AS-IV in attenuating retinopathy induced by diabetes in rats and preliminarily unveiled the therapeutic efficacy of AS-IV in the treatment of DR might be attributed to activation of PI3K-AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV), one of the major compounds extract from Astragalus membranaceus, has shown attractive anti-cancer effects in certain malignancies. Oxidative stress (OS) is considered as a crucial factor in promoting the progression of hepatocellular carcinoma (HCC). In response to OS, nuclear factor erythroid 2-related factor 2 (Nrf2) upregulates and induces heme oxygenase 1 (HO-1) to combat oxidative damages. The phosphorylation of the COOH-terminal of Smad3 (pSmad3C) activates p21 to resist HCC progression, while the phosphorylation of the linker region of Smad3 (pSmad3L) up-regulates c-Myc transcription to exert promoting effect towards HCC. This study aimed to explore whether AS-IV suppresses migration and invasion of human hepatoma HuH-7 cells by regulating Nrf2/HO-1 and TGF-β1/Smad3 pathways. HuH-7 cells were induced with TGF-β1 (9 or 40 pM) to establish HCC model in vitro and pretreated with AS-IV at different concentration (5, 10, and 20 μM) for 24 h. Cell proliferation, migration, invasion, and intracellular reactive oxygen species (ROS) of HuH-7 cells were measured. The expression of Nrf2, pSmad3C, Nrf2/pNrf2, HO-1, pSmad3C/3L, c-Myc, and p21 were detected. Exposure of HuH-7 cells to TGF-β1 enhanced the cell proliferation, migration, invasion, and ROS production. Pretreatment with AS-IV (5, 10, and 20 μM) significantly reduced the cell proliferation, migration, invasion, and ROS production in HuH-7 cells. Furthermore, AS-IV increased the expressions of Nrf2/pNrf2, HO-1, pSmad3C, and p21, meanwhile reduced the expressions of pSmad3L and c-Myc. In conclusion, our study suggested that AS-IV inhibit HuH-7 cells migration and invasion, which related to activate Nrf2/HO-1 pathway, up-regulation pSmad3C/p21 pathway, and down-regulation pSmad3L/c-Myc pathway. The present research supports the notion that AS-IV may be a latent agent for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the mechanism of astragaloside IV (AS-IV) inhibiting the invasion and metastasis of vulvar squamous cell carcinoma (VSCC). Material and methods: MTT and plate colony-formation assays were used to examine the cell proliferation of VSCC (SW962 cell line). Transwell and scratch wound-healing assays were used to analyse cell migration and invasion. Western blot was used to detect the expression of relevant proteins in terms of cell proliferation, invasion and metastasis, as well as the TGF-β1/FAK/AKT signaling pathway. Results: The results showed that AS-IV inhibited the proliferation of SW962 cells in a concentration-dependent manner, as demonstrated by the upregulation of P53 and P21 expression and the downregulation of cyclin D1 expression. AS-IV decreased the ability of cell invasion and metastasis by the downregulation of MMP-2 and MMP-9 expression. When TGF-β1 was added to SW962 cells, the expression of the N-cadherin and Vimentin were upregulated and that of the E-cadherin was downregulated. Subsequently, fibroblast-like elongated spindle-shaped cells appeared, which suggests that TGF-β1 could induce EMT in SW962 cells. Furthermore, the expression of p-FAK, p-AKT, MMP-2 and MMP-9 were upregulated. The expression of these proteins exhibited the opposite effect after AS-IV intervention. Cell invasion and metastasis were suppressed. Conclusions: AS-IV inhibits cell invasion and metastasis in VSCC through the TGF-β1/FAK/AKT signalling pathway. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AGS-IV) is an active constituent of Radix Astragali used in many Traditional Chinese Medicines. This paper describes a sensitive and specific assay for the quantitation of AGS-IV in rat plasma. After solid phase extraction (SPE), samples were analyzed by liquid chromatography electrospray ionization mass spectrometry using a reversed-phase C18 column. The assay was linear in the range 1–500 ng/ml with a limit of detection of 0.5 ng/ml. The recovery was 92.5% and within-day and between-day precision were 3.7–6.0 and 2.8–9.8%, respectively. The assay was applied to a pharmacokinetic study in rat after a single oral dose. The drug was rapidly absorbed and subsequently eliminated according to a biphasic concentration–time curve. [Copyright &y& Elsevier]

Yu-Qing Tan,1,2 Heng-Wen Chen,1,* Jun Li1,* 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, People’s Republic of China; 2Graduate School of Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heng-Wen Chen; Jun Li Email chenhengwen@163.com; 13051458913@163.comAbstract: Cardiovascular disease (CVD), the number one cause of death worldwide, has always been the focus of clinical and scientific research. Due to the high number of deaths each year, it is essential to find alternative therapies that are safe and effective with minimal side effects. Traditional Chinese medicine (TCM) has a long history of significant impact on the treatment of CVDs. The mode of action of natural active ingredients of drugs and the development of new drugs are currently hot topics in research on TCM. Astragalus membranaceus is a commonly used Chinese medicinal herb. Previous studies have shown that Astragalus membranaceus has anti-tumor properties and can regulate metabolism, enhance immunity, and strengthen the heart. Astragaloside IV (AS-IV) is the active ingredient of Astragalus membranaceus, which has a prominent role in cardiovascular diseases. AS-IV can protect against ischemic and hypoxic myocardial cell injury, inhibit myocardial hypertrophy and myocardial fibrosis, enhance myocardial contractility, improve diastolic dysfunction, alleviate vascular endothelial dysfunction, and promote angiogenesis. It can also regulate blood glucose and blood lipid levels and reduce the risk of cardiovascular diseases. In this paper, the mechanism of AS-IV intervention in cardiovascular diseases in recent years is reviewed in order to provide a reference for future research and new drug development.Keywords: Astragalus membranaceus, astragaloside IV, traditional Chinese medicine, cardiovascular diseases, cardiomyocytes

Objective: To investigate the effect of astragaloside IV on cardiac hypertrophy and its regulation on autophagy. Methods: Fifty male Sprague-Dawley rats were randomly divided into sham operation group and abdominal aortic coarctation group(AAC group). There were 10 rats in sham operation group and 40 rats in the AAC group. One week after the operation, there were 32 rats in AAC group, 10 rats in sham group. AAC group was randomly divided into model group, low-dose astragaloside group, high-dose astragaloside group and rapamycin group, 8 rats in each group. Rapamycin group was a positive autophagy contrast agent group. They were given the corresponding solvents once a day by gavage for six weeks. At the end of study, three rats were randomly selected from each group, left ventricular mass index(LVW/BW), cardiac mass index(HW/BW) and the content of hydroxyproline were measured. HE staining, masson staining and sirius red staining were used to observe the morphological changes of myocardium. The expression of LC3II, LC3I, Beclin1, AMPK and mTOR were detected by western blot. Results: Compared with the sham operation group, AAC group showed hypertrophy, LVW/BW, HW/BW, HYP and p-mTOR/mTOR were significantly increased(P<0.05), p-AMPK/AMPK, LC3II/LC3I, Beclin1 were significantly decreased(P<0.05). Compared with the model group, the low-dose astragaloside IV group showed the hypertrophy of cardiomyocytes was relatively light, LVW/BW and HW/BW were significantly decreased (P<0.05), there was no significant difference in HYP and p-mTOR/mTOR(P>0.05), LC3II/LC3I, Beclin1 and p-AMPK/AMPK were significantly increased (P<0.05). Compared with the model group, high-dose astragaloside IV group and rapamycin group showed reduced myocardial hypertrophy, LVW/BW, HW/BW, HYP and p-mTOR/mTOR were significantly decreased (P<0.05), LC3II/LC3I, Beclin1 and p-AMPK/AMPK were significantly increased(P<0.05). Compared with the low-dose astragaloside group, the high-dose astragaloside group showed reduced myocardial hypertrophy, there were significant differences in each index(P<0.05). Compared with rapamycin group, there was no obvious difference in morphology and structure of myocardial cells, LVW/BW, HYP and p-mTOR/mTOR were decreased (P<0.05), HW/BW and p-AMPK/AMPK had no significant difference (P>0.05), LC3II/LC3I and Beclin1 were increased in high-dose astragaloside group (P<0.05). Conclusion: As IV has protective effect on cardiac hypertrophy in a dose-dependent manner and its mechanism may be related to regulate autophagy. [ABSTRACT FROM AUTHOR]

Astragaloside IV is the main active ingredient of Astragalus membranaceus. Studies have found that it can promote the proliferation of osteoblasts and can antagonize the apoptosis of mouse osteoblasts induced by hydrogen peroxide, but its molecular mechanism for the treatment of osteoporosis is still not clear. First, we used 3 online platforms: CTD, PharmMapper and SwissTargetPrediction to retrieve the targets of Astragaloside IV, and collected osteoporosis-related targets. Next, we used Cytoscape 3.7.2 software to construct a visual network diagram of PPI and further screened the key genes of Astragaloside IV in the treatment of osteoporosis using cluster analysis. Finally, after the receptor and ligand were docked, the binding activity was assessed by docking score. We obtained 102 overlapping targets of Astragaloside IV and osteoporosis. According to the node degree value in the PPI network, the top 10 genes were PIK3CA, MAPK1, SRC, STAT3, VEGFA, HSP90AA1, RELA, AKT1, IGF1, EGFR, of which SRC, AKT1, PIK3CA could bind stably to Astragaloside IV. KEGG pathway enrichment results showed that Astragaloside IV treated osteoporosis through 10 main pathways, including PI3K-Akt signaling pathway, FoxO signaling pathway, MAPK pathway, and so on. The classification of these pathways belongs to signal transduction, immune system, development and regeneration and endocrine system. Astragaloside IV is significantly related to several pathways involved in osteoporosis, such as PI3K-Akt, FoxO signaling pathway and MAPK pathway. SRC, AKT1, and PIK3CA can bind stably with Astragaloside IV, and they may be hub genes for the treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Astragaloside IV (ASIV) is the main active component of Astragalus , and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups (n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium–treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition. [ABSTRACT FROM AUTHOR]

IDO1-mediated immune escape can lead to the malignant progression of tumors. However, the precise mechanism of IDO1 remains unclear. This study showed that IDO1 can bind to GBP1 and increase the extracellular secretion of IDO1 with the assistance of GBP1, thereby promoting the malignant proliferation and metastasis of lung cancer. In vitro study showed that the high expression levels of IDO1 and GBP1 in lung cancer cells promoted cell invasion and migration. In vivo study revealed that knock-down of IDO1 and GBP1 inhibited tumor growth and metastasis. In addition, Astragaloside IV reduces the extracellular secretion of IDO1 by blocking the interaction of IDO1 and GBP1, thereby reducing T cell exhaustion and inhibiting tumor progression. These results suggest that blocking the extracellular secretion of IDO1 may prevent T cell exhaustion and thereby enhance the effect of PD-1 inhibitors on cancer treatment. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway. We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10 mg/kg/d) and Astragalus extract (AE) (4.35 g/kg/d, which contained about ASG 10 mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h. The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis. AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway. Image 1 [ABSTRACT FROM AUTHOR]

Gut microbiota and short‐chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography‐mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up‐regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT–NF‐κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS/IV) is one of the extracted components from the traditional Chinese medicine Astragalus which has been demonstrated to have potential capacity for anti-inflammation activity and for treating cardiovascular disease. Our purpose was to determine the function and underlying molecular mechanism of AS/IV in hypoxia/reoxygenation (H/R) injured in cardiomyocytes. Differentially expressed genes (DEGs) were screened using bioinformatic analysis, and the molecular targeting relationship was verified by the dual-luciferase report system. H/R injured cardiomyocytes were employed to explore the effect of AS/IV. QRT-PCR and Western blot analysis were applied to detect the expression of mRNA and proteins, respectively. Additionally, superoxide dismutase (SOD), lactic dehydrogenase (LDH) and MDA (malondialdehyde) levels were detected to determine the oxidative damage. Cell viability was assessed by CCK-8, and flow cytometry was used to evaluate cell apoptosis ratio. TGFBR1 and TLR2 were selected as DEGs. Additionally, AS/IV could enhance cell proliferation and upregulated miR-101a expression, which suppressed TGFBR1 and TLR2 expression in H/R injured cardiomyocytes. Moreover, the results of Western blot exhibited that the downstream genes (p-ERK and p-p38) in the MAPK signaling pathway were suppressed, which meant AS/IV could inhibit this pathway in H/R injured cardiomyocytes. Overall, this study demonstrated AS/IV could attenuate H/R injury in human cardiomyocytes via the miR-101a/TGFBR1/TLR2/MAPK signaling pathway axis, which means that it could serve as a possible alternate for H/R treatment. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling. [ABSTRACT FROM AUTHOR]

Radix Astragali is a traditional Chinese medicine (TCM), which strengthens the efficacy in tonifying Qi after honey-processing. However, a comparative study on the marker compounds in raw and honey-processed Radix Astragali has not been reported. A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method has been established for the analysis of astragaloside IV and calycosin-7-O-β-glucoside from raw and honey-processed Radix Astragali. The method employed silica gel G F254 thin-layer plates as the stationary phase, with chloroform–methanol–water (13:7:2 v/v) as the mobile phase. Following development, the plates were observed under ultraviolet (UV) light at 365 nm. The method was validated for linearity, precision, recovery, limit of detection (LOD), and limit of quantification (LOQ). Recovery of the two compounds was between 99.10% and 99.74%. LOD and LOQ were in the range of 15–42 ng and 45–126 ng for the two compounds, respectively. The method was successfully utilized to analyze the two marker components in raw and honey-processed Radix Astragali. The quantitative results demonstrated that astragaloside IV and calycosin-7-glucoside could be converted into their aglycones in the honey-processing procedure. This established HPTLC method would be sensitive enough and reliable for the comprehensive quality control of raw and processed Radix Astragali. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown. Material and methods: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion. Results: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actin–myosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV. Conclusions: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Astragaloside IV (AS-IV), a natural herbal compound from Astragalus membranaceus, has inhibitory effects on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, and RANKL signal helps to regulate odontoblast differentiation. However, whether and how AS-IV affects odontoblastic differentiation remains unclear.Methods: Lipopolysaccharide (LPS)-stimulated MDPC-23 cells and rat pulpitis were treated with AS-IV, cell viability, and LDH leakage was analyzed by CCK-8 assay and LDH Leakage assay. The production of TNF-α and IL-6 was determined by ELISA and qRT-PCR assay. The expression of alkaline phosphatase (ALP) was detected using an ALP assay kit, and the expression of dentin sialophos-phoprotein (DSPP), dentin matrix protein-1 (DMP1), basic fibroblast growth factor (FGF2), and phosphorylated extracellular signal-regulated kinase (p-ERK) was determined by western blot.Results: AS-IV dose dependently increased in cell viability and decreased the overproduction of TNF-α and IL-6 in LPS-stimulated MDPC-23 cells. AS-IV also counteracted LPS-induced downregulation of ALP, DSPP, and DMP1 in MDPC-23 cells. Furthermore, AS-IV significantly decreased the expression of FGF2 and p-ERK in LPS-stimulated MDPC-23 cells. More important, the addition of FGF2 partly neutralized AS-IV-mediated inhibition of FGF2/ERK signaling, abolished AS-IV-induced reduction of TNF-α and IL-6, and counteracted AS-IV-induced upregulation of DSPP and DMP-1 in these cells. Meanwhile, AS-IV inhibited the excessive production of TNF-α and IL-6, suppressed the downregulation of DSPP and DMP1, and disturbed the up-regulation of FGF2 and p-ERK in the pulp tissues of rat pulpitis model.Conclusions: AS-IV exerted anti-inflammatory and pro-differentiation effects in LPS-stimulated MDPC-23 cells and rat pulpitis via inhibiting the FGF2/ERK signaling pathway. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) has become the major cause of end-stage renal disease increasing the mortality risk of diabetes. Research has demonstrated that the oxidative damage and apoptosis of renal tubular cells is present during DN. Astragaloside IV (AS-IV) has been widely used for the treatment of many diseases, however, the role and mechanism by which AS-IV may ameliorate high glucose-induced apoptosis and oxidative stress of the human proximal tubular cell line HK-2 remains largely unknown. The present study investigated the effect of AS-IV on high glucose-induced apoptosis and oxidative stress in HK-2 cells. Cell viability, apoptosis and protein expression were detected by Trypan blue staining, Cell Counting Kit-8 assay, terminal deoxynucleotidyl transferase 2′-deoxyuridine-5′-triphosphate nick-end labelling, flow cytometry and western blot analyses. In addition, enzymatic activities, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and lipid peroxide (LPO), were measured with the corresponding detection kits. DCFH-DA assay and flow cytometry were performed to detect the production of reactive oxygen species (ROS). Western blot analysis and reverse transcription-quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expressions of the nuclear factor erythroid 2 like 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. The results demonstrated that AS-IV significantly enhanced HK-2 cell viability induced by high glucose in a dose-dependent manner. In addition, AS-IV notably inhibited HK-2 cell apoptosis stimulated by high glucose, which may be associated with inhibition of BCL2 associated X protein, Cleaved-caspase-3 and Cleaved-caspase-9, expression and the promotion of Bcl-2. AS-IV significantly increased the activities of antioxidant enzymes SOD, GSH-Px and CAT, and decreased the high-glucose-induced ROS production in HK-2 cells, in a dose-dependent manner. Finally, it was determined that AS-IV regulated the Nrf2/ARE signaling pathway and inhibited the expression of liver-type fatty acid binding protein. In conclusion, these findings may provide evidence that AS-IV has a potential role for the treatment of DN. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AST-IV) is a major active ingredient of astragalus, with a neuroprotective effect. The current study is aimed to investigate the impact of AST-IV on the M1/M2 microglial activation in response to lipopolysaccharide (LPS) stimulation, how AST-IV attenuated microglia-mediated neuronal damage, and the molecular mechanisms underlying AST-IV's protection of neurons against microglia-mediated neuronal damage. Our results showed that AST-IV partially protected microglia from death evoked by LPS and downregulated the release of pro-inflammatory (M1) mediators including interleukin (IL)-1β, IL-6, tumour necrosis factor α (TNF-α) and nitric oxide, as well as the expression of Toll-like receptors 4 (TLR4), MyD88, and nuclear factor κB (NF-κB) of these cells. In contrast, AST-IV elevated the production of anti-inflammatory cytokine IL-10 and expression of arginase 1, an M2 marker of microglia, whose conditioned medium promoted PC12 neurons survival. These results indicate that AST-IV exerts an anti-inflammatory effect on microglia, possibly through inhibiting TLR4/NF-κB signalling pathways, and protects neurons from microglia-mediated cell death through conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype. [ABSTRACT FROM AUTHOR]

Activation of calcium sensing receptor (CaSR) contributes to cardiac injury, but the underlying mechanism has not yet been examined. Astragaloside IV (AsIV) was previously reported to exhibit protective effects against various myocardial injuries. The aim of the present study was to investigate the underlying mechanism of CaSR in cardiac hypertrophy and apoptosis and to evaluate whether the protective effect of AsIV against myocardial injury is associated with CaSR and its related signaling pathway. In vivo and in vitro myocardial injury was induced by isoproterenol (Iso) or GdCl3 (a CaSR agonist) in rats and heart H9C2 cells. Cardiac cell hypertrophy, apoptosis, function, Mitochondrial Membrane Potential (MMP), mitochondrial ultrastructure, and [Ca2+]i, as well as the protein expression of CaSR, calcium/calmodulin-dependent protein kinase II (CaMKII), calcineurin (CaN), sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a), and the inositol 1,4,5-trisphosphate receptor (IP3R), were measured in vivo and/or in vitro. The results showed that AsIV attenuated cardiac hypertrophy and apoptosis and attenuated impairments in cardiac function, mitochondrial structure, and MMP induced by Iso or GdCl3 in rat myocardial tissue and H9C2 cells. Importantly, AsIV treatment inhibited the enhancement of [Ca2+]i and CaSR expression induced by Iso or GdCl3, an effect similar to that of the CaSR antagonist NPS2143. In addition, AsIV treatment repressed CaSR, CaMKII, and CaN activation and inhibited NFAT-3 nuclear translocation. Mechanistic analysis using lentivirus infection showed that CaSR overexpression activated the CaMKII and CaN signaling pathways and that this response was enhanced by Iso. The results suggested that CaSR-mediated changes in [Ca2+]i and CaMKII and CaN signaling pathways contribute to cardiac hypertrophy and apoptosis and are involved in the protective effect of astragaloside IV against cardiac injury. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV), the major pharmacological extract from Astragalus membranaceus Bunge, possesses a variety of biological activities in the cardiovascular systems. Here, we aimed to evaluate preclinical evidence and possible mechanism of AS-IV for animal models of myocardial ischemia/reperfusion (I/R) injury. Studies of AS-IV in animal models with myocardial I/R injury were identified from 6 databases from inception to May, 2018. The methodological quality was assessed by using CAMARADES 10-item checklist. All the data were analyzed using Rev-Man 5.3 software. As a result, 22 studies with 484 animals were identified. The quality score of studies ranged from 3 to 6 points. Meta-analyses showed AS-IV can significantly decrease the myocardial infarct size and left ventricular ejection fraction, and increase shortening fraction compared with control group (P < 0.01). Significant decreasing of cardiac enzymes and cardiac troponin and increasing of decline degree in ST-segment were reported in one study each (P < 0.05). Additionally, the possible mechanisms of AS-IV for myocardial I/R injury are promoting angiogenesis, improving the circulation, antioxidant, anti-inflammatory and anti-apoptosis. Thus, AS-IV is a potential cardioprotective candidate for further clinical trials of myocardial infarction. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the effect of astragaloside IV on adipose lipolysis and hepatic gluconeogenesis. Methods: High-fat diet (HFD) feeding induced adipose dysfunction with enhanced endogenous glucose production in mice. The effects of Astragaloside IV on lipolysis and hepatic glucose production were investigated. Results: HFD feeding induced cAMP accumulation through reducing PDE3B expression and activity in adipose tissue. As a result, HFD feeding increased adipose lipolysis inmice. Astragaloside IV enhanced Akt phosphorylation and promoted Akt binding to PDE3B to preserve PDE3B content, resultantly reducing adipose cAMP accumulation. Knockdown of Akt1/2 diminished the effect of astragaloside IV on PDE3B induction, indicative of the role of Akt in astragaloside IV action. As a result from blocking of cAMP/PKA signaling, astragaloside IV suppressed hormone-sensitive lipase (HSL) activation and inhibited inflammation-associated adipose lipolysis. Moreover, astragaloside IV reduced ectopic fat deposition in the liver and inhibited FoxO1 activation via regulation of Akt, resultantly restraining excess hepatic glucose production. Conclusion: We showed that preserving PDE3B content by Akt is a key regulation to prevent lipolysis. Astragaloside IV inhibited lipolysis by reducing cAMP accumulation via regulation of Akt/PDE3B, contributing to limiting hepatic lipid deposition and restraining excessive hepatic glucose production. [ABSTRACT FROM AUTHOR]

Background: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. Methods: The ApoE-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. Results: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE-/- mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53- apoptosis pathway and oxidant-antioxidants in the hearts of ApoE-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16INK4a in the hearts of ApoE-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. Conclusion: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress. [ABSTRACT FROM AUTHOR]