PMID: 

Drug Des Devel Ther. 2019 ;13:2579-2589. Epub 2019 Jul 29. PMID: 31440038

Abstract Title: 

Astragaloside IV protects endothelial progenitor cells from the damage of ox-LDL via the LOX-1/NLRP3 inflammasome pathway.

Abstract: 

Functional impairment of endothelial progenitor cells (EPCs) is frequently observed in patients with diabetic vascular complications. Astragaloside IV (ASV) has a significant protective effect against vascular endothelial dysfunction. Thus, this study aimed to investigate the role of ASV on oxidized low-density lipoprotein (ox-LDL)-induced EPCs dysfunction and its potential mechanisms.EPCs were isolated from the peripheral blood of mice and treated with different concentration of ASV (10, 20, 40, 60, 80, 100 and 200µM). ox-LDL was served as a stimulus for cell model. The proliferation and migration, and improved tube formation ability of EPCs were determined. Reactive oxygen species (ROS) production and the levels of inflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-10 and tumor necrosis factor (TNF-α) were measured. The expression oflectin-like oxidized LDL receptor (LOX-1) andNod-like receptor nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3) inflammasome were detected by Western blot analysis.We found ASV treatment alleviated ox-LDL-induced cellular dysfunction, as evidenced by promoted proliferation and migration, and improved tube formation ability. Besides, ASV treatment significantly suppressed ox-LDL-induced ROS production and the levels of inflammatory cytokines. ASV inhibited ox-LDL-induced expression of LOX-1 in a concentration-dependent manner. Overexpression of LOX-1 in EPCs triggered NLRP3inflammasome activation, while inhibition of LOX-1 or treatment with ASV suppressed ox-LDL-induced NLRP3 inflammasome activation. Furthermore, overexpression of LOX-1 in ox-LDL-induced EPCs furtherly impaired cellular function, which could be ameliorated by ASV treatment.Our study showed that ASV may protect EPCs against ox-LDL-induced dysfunction via LOX-1/NLRP3 pathway.

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PMID: 

Front Pharmacol. 2019 ;10:898. Epub 2019 Aug 13. PMID: 31456687

Abstract Title: 

Astragaloside III Enhances Anti-Tumor Response of NK Cells by Elevating NKG2D and IFN-γ.

Abstract: 

Natural killer (NK) cells play an irreplaceable role in the development of colon cancer, in which antitumor function of NK cells was impaired. Astragaloside III is a natural compound from Astragalus that has been shown to have immunomodulatory effects in various systems. However, few studies have evaluated the antitumor effects of Astragaloside III through stimulating systemic immunity and regulating NK cells. In this study, flow cytometry, immunohistochemical analysis, and immunofunctional assays were performed to elucidate the functions of Astragaloside III in restoring antitumor function of NK cells. We demonstrated that Astragaloside III significantly elevated the expression of natural killer group 2D (NKG2D), Fas, and interferon-γ (IFN-γ) production in NK cells, leading to increased tumor-killing ability. Experiments in cell co-culture assays and CT26-bearing mice model further confirmed that Astragaloside III could effectively impede tumor growth by increasing infiltration of NK cells into tumor and upregulating the antitumor response of NK cells. We further revealed that Astragaloside III increased IFN-γ secretion of NK cells by enhancing the expression of transcription factor T-bet. In conclusion, the effective anti-tumor function of Astragaloside III was achieved through up-regulation of the immune response ofNK cells and elevation of NKG2D, Fas, and IFN-γ production.

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PMID: 

Front Pharmacol. 2019 ;10:894. Epub 2019 Aug 15. PMID: 31474858

Abstract Title: 

Astragaloside IV Protects Ethanol-Induced Gastric Mucosal Injury by Preventing Mitochondrial Oxidative Stress and the Activation of Mitochondrial Pathway Apoptosis in Rats.

Abstract: 

Alcohol consumption affects gastric mucosa by multiple and complex mechanisms depending either by direct contact of ethanol or by indirect biological damage induced by its metabolite acetaldehyde. The present study aims at further investigating the mechanism of ethanol-induced gastric mucosa injury and the protective effect of astragaloside IV (AS-IV) in an aspect of mitochondrial oxidative stress and mitochondrial pathway of apoptosis. Using an array of experimental approaches, we have shown that the development of mitochondrial oxidative stress and associated apoptosis play crucial roles in the pathogenesis of gastric injury induced by ethanol. AS-IV inhibits mitochondrial oxidative stress by scavenging accumulation of malondialdehyde and decreasing the consumption of glutathione. AS-IV also prevents ethanol-induced apoptosis by modulating the activity of caspase-3 and caspase-9, the expression of Bax/Bcl-2, and the release of cytochrome C and apoptosis inducing factor. Moreover, AS-IV reduces ethanol-mediated activation of caspase-8 and breakage of Bid. This study thus indicates that AS-IV prevented ethanol-induced gastric damage by blocking activation of mitochondrial oxidative stress and mitochondrial pathway of apoptosis induced by ethanol in the gastric mucosa.

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PMID: 

Biomed Pharmacother. 2019 Sep 2 ;119:109387. Epub 2019 Sep 2. PMID: 31487583

Abstract Title: 

Inhibitory effects of astragaloside IV on silica-induced pulmonary fibrosis via inactivating TGF-β1/Smad3 signaling.

Abstract: 

PURPOSE: To observe the effect of astragaloside ASV (ASV) on silicosis fibroblasts, and further investigate its regulatory mechanism on TGF-β1/Smad3 signaling pathway.METHODS: Silica-induced rats model was established in this study. RT-qPCR was performed to detectα-SMA, Collagen I, Collagen III, Smad2, Smad3 and Smad7 expression. Immunofluorescence was conducted to detect α-SMA, Collagen I, Collagen III and p-Smad3 protein and the nucleoplasmic distribution of p-Smad3.Western-blotting was performed to detect the protein of Smad2, p-Smad2, Smad3, p-Smad3 and Smad7.RESULTS: 20 μg/mL ASV could effectively reduce the expression of α-SMA, Collagen I, Collagen III. TGF-β1 stimulated the proliferation of fibroblasts, promoted phosphorylation of Smad2 and Smad3, and down-regulated Smad7 expression. Among them, continuous phosphorylation of Smad3 is a major factor in causing fibrosis. Besides, ASV can inhibit silica-induced lung fibroblast fibrosis through TGF-β1/Smad3 signaling pathway, thereby inhibiting the formation of silicosis.CONCLUSION: ASV could inhibit the expression of collagen in fibroblasts and the transformation to myofibroblasts, and has an anti-silicosis fibrosis effect, which may be related to the continuous phosphorylation of Smad3 in the TGF-β1/Smad signaling pathway.

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PMID: 

Am J Transl Res. 2019 ;11(8):5029-5038. Epub 2019 Aug 15. PMID: 31497219

Abstract Title: 

Astragaloside IV attenuates renal fibrosis through repressing epithelial-to-mesenchymal transition by inhibiting microRNA-192 expression:andstudies.

Abstract: 

The aim of this study was to investigate the effect of Astragaloside IV (AS-IV) on renal fibrosisand, and further to explore the underlying mechanism. To investigate the effect of AS-IV treatment on renal fibrosis, mouse renal fibrosis model was established by performing unilateral ureteral occlusion (UUO). The mice in the intervention group of AS-IV were given AS-IV 20 mg/(kg/d) on the day after surgery for 7 consecutive days. Then renal sections were stained with hematoxylin and eosin (H&E) to evaluate the degree of fibrosis. Forstudy, human kidney tubular epithelial cells induced by (TGF-β1) were performed to research the protective role of AS-IV in anti-fibrosis. Results form thestudy showed that AS-IV treatment in UUO mice significantly reduced parenchymal loss and tubular atrophy, indicating that AS-IV treatment attenuated renal fibrosis caused by UUO. TGF-β1 treatment significantly increased the expression of α-SMA, vimentin, collagen I, miR-192 and decreased E-cadherin expression in HK-2 cells, suggesting that TGF-β1 stimulated renal tubulointerstitial fibrosis. Moreover, in TGF-β1 stimulated HK-2 cells, AS-IV clearly inhibited the expression levels of α-SMA, vimentin, collagen I, and miR-192 in a dose-dependent fashion while increased the expression level of E-cadherin in the same manner, indicating that AS-IV functioned the inhibitory role in renal tubulointerstitial fibrosis. Interestingly, we noted that ZEB2 was a direct target of miR-192. The effects of AS-IV on the expression of α-SMA, vimentin, collagen I and E-cadherin were inhibited by miR-192 mimic and aggravated by miR-192 inhibitor. Taken together, our results provided evidence that AS-IV could effectively protect kidney against epithelial fibrosis, and this renoprotective effect involved miR-192. Therefore, AS-IV might be considered as a potential and promising candidate drug for the treatment of renal epithelial fibrosis.

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PMID: 

Med Sci Monit. 2019 Sep 23 ;25:7158-7168. Epub 2019 Sep 23. PMID: 31545785

Abstract Title: 

Astragaloside IV Alleviates the Myocardial Damage Induced by Lipopolysaccharide via the Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB)/Proliferator-Activated Receptor α (PPARα) Signaling Pathway.

Abstract: 

BACKGROUND We previously reported that astragaloside IV (As-IV) can alleviate myocardial damage induced by lipopolysaccharide (LPS). However, the anti-inflammatory effects of As-IV following LPS stimulation in mice and H9C2 cardiomyocytes remain unclear. The present study was designed to explore the mechanism of action of As-IV. MATERIAL AND METHODS In vivo, C57BL/6J mice were randomly divided into 5 groups: the control group, the LPS group (10 mg/kg), and 3 LPS groups receiving different doses of As-IV (20, 40, and 80 mg/kg). The protective effect of As-IV on LPS-stimulated H9C2 cardiomyocytes was evaluated in vitro. Cardiac function was detected by echocardiography, and H&E staining was used to evaluate morphologic changes. Cardiomyocyte viability was detected by MTT assay. ELISA was used to detect free fatty acid (FFA), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor alpha (TNF-alpha) levels in mouse serum and in cell supernatant. Adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents in myocardial tissues and cells were detected by high-performance liquid chromatography. ATP5D and TLR4/NF-kappaB/PPARalphasignaling pathway proteins (TLR4, NF-kappaB, p65, and PPARalpha) were detected by Western blotting. RESULTS As-IV significantly improved cardiac function, myocardial cell viability, and pathological changes and reduced FFA, IL-1ß, IL-6, and TNF-alpha levels. The ATP/AMP ratio in the cardiac tissues of mice and in H9C2 cardiomyocytes was increased compared to that in the LPS group. In addition, As-IV enhanced ATP synthase and PPARalpha protein expression. In H9C2 cardiomyocytes, the p65-specific inhibitor BAY11-7082 exerted similar effects as As-IV. CONCLUSIONS As-IV alleviates LPS-induced myocardial damage by modulating TLR4/NF-kappaB/PPARalpha signaling-mediated energy biosynthesis.

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PMID: 

Pharmacology. 2019 Sep 25:1-12. Epub 2019 Sep 25. PMID: 31554002

Abstract Title: 

Astragaloside IV Attenuates Lipopolysaccharides-Induced Pulmonary Epithelial Cell Injury through Inhibiting Autophagy.

Abstract: 

BACKGROUND: Astragaloside IV has shown its promising effect on acute respiratory distress syndrome (ARDS).OBJECTIVES: We aim to explore whether astragaloside IV is effective for ARDS treatment in a lipopolysaccharides (LPS)-induced cell model and whether autophagy is involved in the therapeutic function of astragaloside IV.METHODS: MLE-12 cells were induced by LPS to construct an ARDS model in vitro. Cell viability was estimated by cell counting kit-8 and cell apoptosis by flow cytometry. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by enzyme-linked immunosorbent assay kit. The expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, zonula occludens (ZO)-1, Beclin-1 and autophagy-related (atg) 5 mRNA was evaluated by quantitative PCR, and the expression of ZO-1, microtubule-associated proteins 1A/1B light chain 3B (LC3B) I and, LC3B II protein by Western blot.RESULTS: LPS effectively inhibited cell viability and LC3B I expression and enhanced LC3B II, Beclin-1 and atg5 expressions in MLE-12 cells. In LPS-induced ARDS cell model, astragaloside IV up-regulated cell viability, SOD activity and ZO-1 and LC3B I expressions but down-regulated cell apoptosis, TNF-α, IL-6, LC3B II, Beclin-1 and atg5 expressions and LDH and MDA levels. 3-methyladenine promoted cell viability and ZO-1 expression, down-regulated Beclin-1 and atg5 expression, while Rapamycin (Rap) had an opposite effect. Astragaloside IV suppressed cell viability and ZO-1 expression after the Rap treatment.CONCLUSIONS: Astragaloside IV might suppress autophagy initiation directly or indirectly through suppressing the oxidative stress and inflammatory response, which further enhances the cell viability and tight junction and reduces apoptosis in LPS-stimulated pulmonary endothelial ARDS cell model, thus exerting its therapeutic function in ARDS.

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PMID: 

Biochem J. 2007 Aug 1 ;405(3):559-68. PMID: 17456048

Abstract Title: 

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies.

Abstract: 

The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes.

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PMID: 

J Cell Physiol. 2002 Jul ;192(1):16-22. PMID: 12115732

Abstract Title: 

Insights into electromagnetic interaction mechanisms.

Abstract: 

Low frequency (

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PMID: 

Arch Med Res. 2011 May ;42(4):261-7. PMID: 21820603

Abstract Title: 

Effects of a 900-MHz electromagnetic field on oxidative stress parameters in rat lymphoid organs, polymorphonuclear leukocytes and plasma.

Abstract: 

BACKGROUND AND AIMS: The present study investigated the effects of a 900-MHz electromagnetic field (EMF) for 2 h/day for 45 days on lymphoid organs (spleen, thymus, bone marrow), polymorphonuclear leukocytes (PMNs) and plasma of rats, focusing on changes in the enzymatic and nonenzymatic antioxidant system. We determined whether there is any difference between immature and mature rats in terms of oxidative damage caused by EMF and tested recovery groups to determine whether EMF-induced damage is reversible in immature and mature rats.METHODS: Twenty four immature and 24 mature rats were divided randomly and equally into six groups as follows: two control groups, immature (2 weeks old) and mature (10 weeks old); two groups were exposed to 900 MHz (28.2± 2.1 V/m) EMF for 2 h/day for 45 days. Two recovery groups were kept for 15 days after EMF exposure.RESULTS: Substantial, deleterious biochemical changes were observed in oxidative stress metabolism after EMF exposure. Antioxidant enzyme activity, glutathione levels in lymphoid organs and the antioxidant capacity of the plasma decreased, but lipid peroxidation and nitric oxide levels in PMNs and plasma and also myeloperoxidase activity in PMNs increased. Oxidative damage was tissue specific and improvements seen after the recovery period were limited, especially in immature rats.CONCLUSIONS: In the present study, much higher levels of irreversible oxidative damage were observed in the major lymphoid organs of immature rats than in mature rats.

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