Astragaloside IV

Names

[ Name ]:
Astragaloside IV

[Synonym ]:
Astragalus Polysaccharides
(3β,6α,9β,16β,20R,24S)-16,25-Dihydroxy-3-(β-D-xylopyranosyloxy)-20,24-epoxy-9,19-cyclolanostan-6-yl β-D-glucopyranoside
ASTRAGALOSIDE
Astrasieversianin XIV
Astragalus extract
Astragaloside IV
β-D-Glucopyranoside, (3β,6α,9β,16β,20R,24S)-20,24-epoxy-16,25-dihydroxy-3-(β-D-xylopyranosyloxy)-9,19-cyclolanostan-6-yl
cyclosieversioside F
cyclosiversioside F
MFCD07368617

Biological Activity

[Description]:

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.

[Related Catalog]:

Signaling Pathways >> MAPK/ERK Pathway >> ERK

Signaling Pathways >> Stem Cell/Wnt >> ERK

Signaling Pathways >> MAPK/ERK Pathway >> JNK

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

Natural Products >> Terpenoids and Glycosides

Research Areas >> Cancer

[Target]

MMP-2

MMP-9

ERK1

ERK2

JNK

[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].

[Kinase Assay]

Briefly, MDA-MB-231 cells treated as indicated or tumor tissues are harvested and lysed in Mg2+ lysis buffer containing 50 mM Tris (pH 7.5), 10 mM MgCl2, 0.5 M NaCl, and protease inhibitor cocktail. Equal amounts of lysates are incubated with PAK-PBD beads at 4°C for 1 h. PAK-PBD beads are pelleted by centrifugation and washed with ish buffer containing 25 mM Tris (pH 7.5), 30 mM MgCl2, 40 mM NaCl. Active Rac1 is detected by western blotting.

[Cell Assay]

Cell viability is determined by CCK-8 assay. To be brief, cultured NSCLC cells are seeded into 96-well plates at the density of 4×104 (cells/well). Then 10 µL⁄well CCK8 solution is added and incubated in dark at 37°C for another 2 h. The absorbance is determined with the wavelength of 490 nm.

[Animal admin]

Transient cerebral ischemia and reperfusion is prepared by BCCAO, as BCCAO is considered an ideal model to study transient cerebral ischemia and reperfusion injury-mediated inflammatory response. Mice are randomLy divided into the Sham, Model, Astragaloside IV (10 mg/kg) and Astragaloside IV (20 mg/kg) treatment groups. The Astragaloside IV treatment groups are intragastrically administered 7 days before the surgery and terminated on the day of sacrifice. On the day of the surgery, Astragaloside IV is administrated 2 h prior to ischemia. The Sham-operated and Model groups are treated with distilled water. After the mice are anesthetized with an intraperitoneal injection of chloral hydrate (350 mg/kg), the bilateral common carotid arteries are exposed and carefully separated with a small ventral neck incision and occluded twice (20 min each) with ligated surgical silk as described previously with minor modifications. There is a 10 min reperfusion period between the two occlusion periods (ischemia 20 min − reperfusion 10 min − ischemia 20 min). Sham-operated mice are subjected to the same surgical operation without the surgical silk ligation. Mouse body temperature is maintained at 37±0.5°C during the surgery with heating equipment until recovery from the anesthesia.

[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

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
895.7±65.0 °C at 760 mmHg

[ Melting Point ]:
295-296ºC

[ Molecular Formula ]:
C₄₁H₆₈O₁₄

[ Molecular Weight ]:
784.970

[ Flash Point ]:
495.5±34.3 °C

[ Exact Mass ]:
784.460938

[ PSA ]:
228.22000

[ LogP ]:
1.96

[ Vapour Pressure ]:
0.0±0.6 mmHg at 25°C

[ Index of Refraction ]:
1.621

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Safety Phrases ]:
S22-S24/25

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2932999099

Customs

[ HS Code ]: 2932999099

[ Summary ]:
2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

[Protective effect and mechanism of astragaloside IV on oxidative stress injury of mesangial cells].

Zhongguo Zhong Yao Za Zhi 38(5) , 725-30, (2013)

To study the protective effect of astragaloside IV (AS IV) on H2O2 induced human mesangial cells (HMC), and further explore its molecular mechanism.The cultured mesangial cells were divided into 5 gro...

Astragaloside IV inhibited the activity of CYP1A2 in liver microsomes and influenced theophylline pharmacokinetics in rats.

J. Pharm. Pharmacol. 65(1) , 149-55, (2013)

With the growing popularity of herbal and natural medicinal products, attention has turned to possible interactions between these products and pharmaceutical drugs. In this study, we examined whether ...

Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro.

Exp. Biol. Med. (Maywood.) 239(10) , 1310-24, (2014)

Astragaloside IV (AS-IV) is a major active ingredient from Radix astragali, which has been considered as a renoprotective agent; however, its molecular mechanisms are unclear. Thus, we designed to inv...