||Astragaloside IV can protect the myocardium against ischemia/reperfusion injury, inhibit adenovirus replication and apoptosis in A549 cells in vitro, has anti-fibrotic effect against systemic sclerosis, and may be useful in ameliorating food-induced metabolic syndrome and membranous nephropathy. It suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.|
||p65 | NF-kB | TGF-β/Smad | Calcium Channel | TNF-α | LTR | Bcl-2/Bax | Caspase | IL Receptor | Antifection|
|Pharmacology. 2008;81(4):325-32. |
|Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes via the sarcoplasmic reticulum Ca-ATPase.[Pubmed: 18349554 ]|
|Although Astragaloside IV, a saponin isolated from Astragalus membranaceus, has been shown to protect the myocardium against ischemia/reperfusion injury, its effect on the status of sarcoplasmic reticulum (SR) Ca2+ transport in the injured myocardium remains largely unknown.
METHODS AND RESULTS:
In this study, we investigated whether in cultured cardiomyocytes subjected to hypoxia and reoxygenation (H/R) administration of Astragaloside IV during H/R attenuates the myocardial cell injury and prevents changes in Ca2+ handling activities and gene expression of SR Ca2+ pump. Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation. Myocyte injury was determined by the release of cardiac troponin I in supernatant. Astragaloside IV significantly inhibited cardiac troponin I release after H/R in a dose-dependent manner. The diastolic [Ca2+]i measured with Fura-2/AM was significantly increased after reoxygenation. Astragaloside IV prevented the rise of diastolic [Ca2+]i and the depression of caffeine-induced Ca2+ transients caused by H/R. Furthermore, the observed depressions in SR Ca2+-ATPase activity as well as the mRNA and protein expression of SR Ca2+-ATPase in hypoxic-reoxygenated cardiomyocytes were attenuated by Astragaloside IV treatment.
These results suggest that the beneficial effect of Astragaloside IV in H/R-induced injury may be related to normalization of SR Ca2+ pump expression and, thus, may prevent the depression in SR Ca2+ handling.
|J Pharm Pharmacol. 2011 May;63(5):688-94. |
|Astragaloside IV inhibits adenovirus replication and apoptosis in A549 cells in vitro.[Pubmed: 21492171 ]|
|Astragaloside IV, purified from the Chinese medical herb Astragalus membranaceus (Fisch) Bge and Astragalus caspicus Bieb, is an important natural product with multiple pharmacological actions. This study investigated the anti-ADVs effect of Astragaloside IV on HAdV-3 (human adenovirus type 3) in A549 cell.
METHODS AND RESULTS:
CPE, MTT, quantitative real-time PCR (qPCR), flow cytometry (FCM) and Western blot were apply to detect the cytotoxicity, the inhibition and the mechanisms of Astragaloside IV on HAdV-3.
TC(0 ) of Astragaloside IV was 116.8 μm, the virus inhibition rate from 15.98% to 65.68% positively was correlated with the concentration of Astragaloside IV from 1.25 μm to 80 μm, IC50 (the medium inhibitory concentration) was 23.85 μm, LC50 (lethal dose 50% concentration) was 865.26 μm and the TI (therapeutic index) was 36.28. qPCR result showed Astragaloside IV inhibited the replication of HAdV-3. Flow FCM analysis demonstrated that the anti-HAdV-3 effect was associated with apoptosis. Astragaloside IV was further detected to reduce the protein expressions of Bax and Caspase-3 and increasing the protein expressions of Bcl-2 using western blotting, which improved the anti-apoptosis mechanism of Astragaloside IV on HAdV-3.
Our findings suggested that Astragaloside IV possessed anti-HAdV-3 capabilities and the underlying mechanisms might involve inhibiting HAdV-3 replication and HAdV-3-induced apoptosis.
|PLoS One. 2015 Mar 4;10(3):e0118759. |
|Astragaloside IV Protects against Isoproterenol-Induced Cardiac Hypertrophy by Regulating NF-κB/PGC-1α Signaling Mediated Energy Biosynthesis.[Pubmed: 25738576]|
|We previously reported that Astragaloside IV (ASIV), a major active constituent of Astragalus membranaceus (Fisch) Bge protects against cardiac hypertrophy in rats induced by isoproterenol (Iso), however the mechanism underlying the protection remains unknown. Dysfunction of cardiac energy biosynthesis contributes to the hypertrophy and Nuclear Factor κB (NF-κB)/Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α (PGC-1α) signaling gets involved in the dysfunction.
METHODS AND RESULTS:
The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-κB/PGC-1α signaling mediated energy biosynthesis. Sprague-Dawley (SD) rats or Neonatal Rat Ventricular Myocytes (NRVMs) were treated with Iso alone or in combination with ASIV. The results showed that combination with ASIV significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight and Left ventricular weight/body weight, improved the cardiac hemodynamics, down-regulated mRNA expression of Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP), increased the ratio of ATP/AMP, and decreased the content of Free Fat Acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with ASIV significantly decreased the surface area and protein content, down-regulated mRNA expression of ANP and BNP, increased the ratio of ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, ASIV increased the protein expression of ATP5D, subunit of ATP synthase and PGC-1α, inhibited translocation of p65, subunit of NF-κB into nuclear fraction in both rats and NRVMs compared with Iso alone. Parthenolide (Par), the specific inhibitor of p65, exerted similar effects as ASIV in NRVMs. Knockdown of p65 with siRNA decreased the surface areas and increased PGC-1α expression of NRVMs compared with Iso alone.
The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-κB/PGC-1α signaling mediated energy biosynthesis.
|Cell Physiol Biochem. 2014;34(6):2105-16. |
|Anti-fibrotic effects of Astragaloside IV in systemic sclerosis.[Pubmed: 25562158]|
|To evaluate the anti-fibrotic effects of Astragaloside IV in systemic sclerosis.
METHODS AND RESULTS:
Treated or untreated systemic sclerosis (SSc) and normal fibroblast isolated from corresponding pairs were utilized to detect expression of collagen and fibronectin by western blot, quantitative real-time RT-PCR (RT-qPCR), immunofluorescence staining and histopathological examination. SSc mouse model induced by bleomycin was used to evaluate the effects of the drug in vivo.
Compared to normal fibroblast (NF), the expression of collagen and fibronectin in SSc (SScF) dramatically increased, and this could be reduced by Astragaloside IV (AST) in a dose- or time-dependent manner at both protein and mRNA levels. Administration of Astragaloside IV consistently decreased collagen formation and partially restored the structure, as well as suppressing collagen and fibronectin expression in the skin lesions of SSc-model mice. Mechanistically, Astragaloside IV-induced fibrosis reduction may be due to deregulation of Smad 3/Fli-1, the major mediators of the fibrotic response and key molecules for TGF-β signaling. Astragaloside IV also decreased the level of p-SMAD3 and completely blocked its relocation into the nuclei.
Astragaloside IV attenuates fibrosis by inhibiting the TGF-β-Smads3 axis in systemic sclerosis.
|Phytother Res. 2012 Jun;26(6):892-8. |
|Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway.[Pubmed: 22086717 ]|
|Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood.
METHODS AND RESULTS:
Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and Astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex.
In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase.