Astragaloside IV

The root of Astragalus membranaceus (Fisch.) Bunge

Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.

In Vitro:Astragaloside IV (10, 20, 40 ng/mL) inhibits NSCLC cell growth, whereas low concentrations of astragaloside IV (1, 2.5, 5 ng/mL) has no obvious cytotoxicity on cell viability. Moreover, combined treatment with astragaloside IV significantly increases chemosensitivity to cisplatin in NSCLC cells. On the molecular level, astragaloside IV co-treatment significantly inhibits the mRNA and protein levels of B7-H3 in the presence of cisplatin[2]. Astragaloside IV inhibits the viability and invasive potential of MDA-MB-231 breast cancer cells, suppresses the activation of the mitogen activated protein kinase (MAPK) family members ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2 and -9[4].

In Vivo:Astragaloside IV (10, 20 mg/kg, p.o.) exhibits a potent ability to prevent cognitive deficits induced by transient cerebral ischemia and reperfusion. Astragaloside IV (10 mg/kg) and Astragaloside IV (20 mg/kg) can significantly decrease the levels of these cytokines compared to the Model group. Astragaloside IV significantly inhibits the level of TLR4 and its downstream proteins, suggesting that both MyD88-dependent and -independent pathways play important roles in the anti-inflammatory effects of Astragaloside IV. Astragaloside IV attenuates NLRP3 and cleaved-caspase-1 expression, and reduces Iba1 protein expression[1]. In the mice model, the high-dose astragaloside IV group has a significant increase in the 48-hour survival rate [60% (9/15) vs 13.3% (2/15), P < 0.05], significant reductions in the serum ALT and AST levels (P < 0.01), and significant reductions in liver histopathological indices and the degree of apoptosis of hepatocytes (P < 0.01), as well as a significant reduction in the content of MDA in liver homogenate (P < 0.01) and a significant increase in the activity of SOD[3].

References:
[1]. Li M, et al. Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci Lett. 2016 Dec 20. pii: S0304-3940(16)30994-6 [2]. He CS, et al. Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3. Cell Physiol Biochem. 2016;40(5):1221-1229. Epub 2016 Dec 14. [3]. Liu L, et al. [Protective effect of astragaloside IV against acute liver failure in experimental mice]. Zhonghua Gan Zang Bing Za Zhi. 2016 Oct 20;24(10):772-777. [4]. Jiang K, et al. Astragaloside IV inhibits breast cancer cell invasion by suppressing Vav3 mediated Rac1/MAPK signaling. Int Immunopharmacol. 2016 Dec 5;42:195-202

Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway.[Pubmed:22086717]

Phytother Res. 2012 Jun;26(6):892-8.

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. 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.

Astragaloside IV inhibits adenovirus replication and apoptosis in A549 cells in vitro.[Pubmed:21492171]

J Pharm Pharmacol. 2011 May;63(5):688-94.

OBJECTIVES: 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: 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. KEY FINDINGS: TC(0 ) of Astragaloside IV was 116.8 microm, the virus inhibition rate from 15.98% to 65.68% positively was correlated with the concentration of Astragaloside IV from 1.25 microm to 80 microm, IC50 (the medium inhibitory concentration) was 23.85 microm, LC50 (lethal dose 50% concentration) was 865.26 microm 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. CONCLUSIONS: 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.

Anti-fibrotic effects of Astragaloside IV in systemic sclerosis.[Pubmed:25562158]

Cell Physiol Biochem. 2014;34(6):2105-16.

OBJECTIVE: To evaluate the anti-fibrotic effects of Astragaloside IV in systemic sclerosis. METHODS: 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. RESULTS: 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-beta signaling. Astragaloside IV also decreased the level of p-SMAD3 and completely blocked its relocation into the nuclei. CONCLUSION: Astragaloside IV attenuates fibrosis by inhibiting the TGF-beta-Smads3 axis in systemic sclerosis.

Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-small ka, CyrillicB signaling pathway in isoproterenol-induced myocardial hypertrophy.[Pubmed:24432369]

J Ethnopharmacol. 2013 Dec 12;150(3):1062-70.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV (As IV) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The protective effect of Astragalus membranaceus on myocardial hypertrophy has been extensively proved. To test the hypothesis that Astragaloside IV can ameliorate the myocardial hypertrophy and inflammatory effect induced by beta-adrenergic hyperactivity, we carried out in vivo and in vitro experiments. MATERIAL AND METHODS: In in vivo study, the isoproterenol (Iso) (5 mg kg(-1) d(-1)) was used as a model of myocardial hypertrophy by intraperitoneal injection. SD rats were randomly assigned to following six groups: A: the control; B: Iso group; C: Iso plus As IV 20 mg kg(-1) d(-1); D: Iso plus As IV 40 mg kg(-1) d(-1); E: Iso plus As IV 80 mg kg(-1) d(-1); F: Iso plus Propranolol 40 mg kg(-1) d(-1). In in vitro study, cultured neonatal rat cardiomyocytes were pretreated with As IV (3, 10, 30 mu mol L(-1)), Propranolol (2 mu mol L(-1)) and BAY11-7082 (5 mu mol L(-1)) for 30 min, and then incubated with Iso (10 mu mol L(-1)) for 48 h. For the rats in each group, the heart mass index (HMI) and the left ventricular mass index (LVMI) were measured. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IkappaBalpha and p65 were quantified by Western blot, and the level of TNF-alpha and IL-6 were measured by ELISA. RESULTS: In vivo: Comparing the Iso group to the control, the HMI, LVMI, TDM were significantly increased; the protein expression of TLR4 and p65 were increased, while the IkappaBalpha were decreased; the expression of ANP, TLR4 mRNA, and TNF-alpha, IL-6 in serum were significantly increased. These changes could be partly prevented by As IV and Pro. In vitro: the over-expression of the cell size, total protein content could remarkably down-regulated by As IV and Pro, and the results of RT-PCR, Western blot and ELISA were similar to those of in vivo. CONCLUSIONS: The results of these studies indicate that Astragaloside IV has good protective effect on myocardial hypertrophy induced by isoproterenol. More specifically, the cardioprotection is related to inhibiting the TLR4/NF-small ka, CyrillicB signaling pathway and the attenuating inflammatory effect.

Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-kappaB/PGC-1alpha signaling mediated energy biosynthesis.[Pubmed:25738576]

PLoS One. 2015 Mar 4;10(3):e0118759.

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 kappaB (NF-kappaB)/Peroxisome Proliferator-Activated Receptor-gamma Coactivator 1alpha (PGC-1alpha) signaling gets involved in the dysfunction. The present study was designed to investigate the mechanism by which ASIV improves the cardiac hypertrophy with focuses on the NF-kappaB/PGC-1alpha 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-1alpha, inhibited translocation of p65, subunit of NF-kappaB 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-1alpha expression of NRVMs compared with Iso alone. The results suggested that ASIV protects against Iso-induced cardiac hypertrophy through regulating NF-kappaB/PGC-1alpha signaling mediated energy biosynthesis.

Astragaloside IV improved intracellular calcium handling in hypoxia-reoxygenated cardiomyocytes via the sarcoplasmic reticulum Ca-ATPase.[Pubmed:18349554]

Pharmacology. 2008;81(4):325-32.

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. 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.

Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation.[Pubmed:25728713]

J Cell Mol Med. 2015 Apr;19(4):850-64.

Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41 H68 O14 , MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-kappaB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-kappaB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC.

Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.

Astragaloside IV,84687-43-4,Astrasieversianin XIV; Astraversianin XIV; Cyclosieversioside F,Natural Products, buy Astragaloside IV , Astragaloside IV supplier , purchase Astragaloside IV , Astragaloside IV cost , Astragaloside IV manufacturer , order Astragaloside IV , high purity Astragaloside IV