|Description:||1. Cycloastragenol and astragaloside IV can suppress ROS-associated ER stress and then inhibit TXNIP/NLRP3 inflammasome activation with regulation of AMPK activity, and thereby ameliorate endothelial dysfunction by inhibiting inflammation and reducing cell apoptosis. |
2. Cycloastragenol stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression, cycloastragenol may have a novel therapeutic role in depression.
3. Cycloastragenol can suppress the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.
4. Cycloastragenol and astragaloside IV have been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity, they also may exert their cellular effects through the activation of the Src/MEK/ERK pathway.
5. Cycloastragenol can remarkably inhibit CYP3A4 and activate CYP2E1 in rats.
6. Cycloastragenol has been shown to extend T cell proliferation by increasing telomarase activity showing that it may also help delay the onset of cellular aging; it is an extraordinary wound healing agent; it inhibits the apoptosis of PC12 induced by 6-OHDA, may be as potential neuroprotective agents in the treatment of Parkinson's disease.
|Targets:||ROS | AMPK | IL Receptor | ERK | MEK | Src | cAMP | Bcl-2/Bax | Telomerase|
|Source:||The root of Astragalus membranaceus (Fisch.) Bunge|
|Solvent:||Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.|
|Storage:||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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|After receiving:||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.|
|1 mg||5 mg||10 mg||20 mg||25 mg|
|1 mM||2.0379 mL||10.1893 mL||20.3786 mL||40.7573 mL||50.9466 mL|
|5 mM||0.4076 mL||2.0379 mL||4.0757 mL||8.1515 mL||10.1893 mL|
|10 mM||0.2038 mL||1.0189 mL||2.0379 mL||4.0757 mL||5.0947 mL|
|50 mM||0.0408 mL||0.2038 mL||0.4076 mL||0.8151 mL||1.0189 mL|
|100 mM||0.0204 mL||0.1019 mL||0.2038 mL||0.4076 mL||0.5095 mL|
J Ethnopharmacol. 2015 Apr 25. pii: S0378-8741(15)00296-2.
|Astragaloside IV and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in the endothelium.[Pubmed: 25922268]|
|ETHNOPHARMACOLOGICAL RELEVANCE: Astragaloside IV and Cycloastragenol are present together in Astragalus membranaceus Moench (Fabaceae) and this study aims to simultaneously investigate their regulation of endothelial homeostasis in the setting of endoplasmic reticulum stress (ER stress). MATERIAL AND METHODS: We stimulated endothelial cells with palmitate (PA 100μM) to evoked ROS-associated ER stress and observed the effects of astragaloside IV and Cycloastragenol on thioredoxin-interacting protein (TXNIP) expression, NLRP3 inflammasome activation and mitochondrion-dependent apoptosis. RESULTS: Astragaloside IV and Cycloastragenol inhibited ROS generation and attenuated ER stress inducer IRE1α phosphorylation, indicating the inhibition of ROS-associated ER stress. In response to ER stress, TXNIP expression increased, accompanied with NLRP3 induction and increased IL-1β and IL-6 production, but these alternations were reversed by treatment with astragaloside IV and Cycloastragenol, demonstrating the inhibitory effects of astragaloside IV and Cycloastragenol on TXNIP/NLRP3 inflammasome activation. Inflammasome activation led to mitochondrial cell death in endothelial cells, whereas astragaloside IV and Cycloastragenol restored the loss of the mitochondrial membrane potential with inhibition of caspase-3 activity, and thereby protected cells from ER stress-induced apoptosis. Astragaloside IV and Cycloastragenol enhanced AMPK phosphorylation and AMPK inhibitor compound C diminished their beneficial effects, indicative of the potential role of AMPK in their regulation. CONCLUSIONS: Astragaloside IV and Cycloastragenol suppressed ROS-associated ER stress and then inhibited TXNIP/NLRP3 inflammasome activation with regulation of AMPK activity, and thereby ameliorated endothelial dysfunction by inhibiting inflammation and reducing cell apoptosis. Simultaneous investigations further showed that astragaloside IV and Cycloastragenol were equally effective in regulation of endothelial homeostasis.|
Biochem Biophys Res Commun. 2014 Jul 18;450(1):306-11.
|Cycloastragenol, a triterpene aglycone derived from Radix astragali, suppresses the accumulation of cytoplasmic lipid droplet in 3T3-L1 adipocytes.[Pubmed: 24942874 ]|
|Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 μM. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 μM. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 μM. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.|
Planta Med. 2012 Jan;78(2):115-21.
|Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types.[Pubmed: 22083896 ]|
|Two Chinese herb-derived small molecule telomerase activators, astragaloside IV (AG-IV) and Cycloastragenol (CAG), have recently been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity. Here, we examined the signaling mechanism of AG-IV and CAG. Telomerase activity in human embryonic kidney HEK293 fibroblasts was increased upon treatment with increasing concentrations of AG-IV or CAG. Both compounds induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) in a time- and dose-dependent manner in HEK293 cells and HEK-neo keratinocytes. AG-IV and CAG also stimulated ERK phosphorylation in other cell lines of lung, brain, mammary, endothelial, and hematopoietic origins. Use of selective inhibitors and dominant negative mutants revealed the involvement of c-Src, MEK (ERK kinase), and epidermal growth factor receptor in CAG-induced ERK phosphorylation. Our data indicate that AG-IV and CAG may exert their cellular effects through the activation of the Src/MEK/ERK pathway.|
|Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management.[Pubmed: 25095809]|
|Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that Cycloastragenol stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, Cycloastragenol promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of Cycloastragenol prompted evaluation of its potential application in the treatment of neurological disorders. Accordingly, Cycloastragenol induced telomerase activity and cAMP response element binding (CREB) activation in PC12 cells and primary neurons. Blockade of CREB expression in neuronal cells by RNA interference reduced basal telomerase activity, and Cycloastragenol was no longer efficacious in increasing telomerase activity. Cycloastragenol treatment not only induced the expression of bcl2, a CREB-regulated gene, but also the expression of telomerase reverse transcriptase in primary cortical neurons. Interestingly, oral administration of Cycloastragenol for 7 days attenuated depression-like behavior in experimental mice. In conclusion, Cycloastragenol stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, Cycloastragenol may have a novel therapeutic role in depression. © 2014 S. Karger AG, Basel.|
Chinese Journal of New Drugs, 2014, 23(4):476-9.
|Effect of continuous oral cycloastragenol on the activity of cytochrome P450 enzymes in rats[Reference: WebLink]|
|Objective: To determine the effect of Cycloastragenol (CAG) on cytochrome P450 enzyme subtypes of rat liver microsomes. Methods: Rats were treated with CAG (40 mg·kg-1·d-1) for 7 days to induce hepatic microsomal enzyme. Cocktail probe substrates were incubated with liver microsomes in vitro. Then, the metabolic elimination percentages of the five probe substrates metoprolol, aminophenylsulfone, chlorzoxazone, phenacetin and tolbutamide were determined by HPLC. The effect of CAG on the enzymatic activity of rat liver microsomal CYP450s was evaluated. Results: Compared with the control, CAG obviously activated CYP2E1, and remarkably inhibited CYP3A4. However, CAG did not significantly affect CYP2D6, CYP1A2 and CYP2C9. The IC50 of CYP3A4 was 12.13 μmol·L-1, and inhibition type was competitive inhibition. Conclusion: CAG can remarkably inhibit CYP3A4 and activate CYP2E1.|
Planta Med., 2011, 77(12):1444.
|Protective Effects of Astragaloside IV and Cycloastragenol in 6-hydroxydopamin (6-OHDA)-Induced Neurotoxicity in PC12 Cells[Reference: WebLink]|
|Cycloastragenol (CG), which is a minor metabolite mostly found in its glycosidic form, was obtained from AST-IV via hydrolysis reaction. CG has been shown to extend T cell proliferation by increasing telomarase activity showing that it may also help delay the onset of cellular aging (1). Indeed, recently, CG has been introduced to the market as a new generation antiaging molecule. Moreover our studies proved CG as an extraordinary wound healing agent (2). Although AST-IV's neuroprotective effects on Parkinson's disease was reported previously, there has been no data for CG. The aim of this study was to investigate the protective effects of AST-IV and CG on neurotoxicity induced by 6-hydroxydopamin (6-OHDA) in PC12 cells, an excepted in vitro model for Parkinson's disease. The cells were seeded on tissue culture plates for 24h. After 24 hours, they were incubated with AST-IV (0.1μM-1 fM) and CG (0.1μM-1 fM) for 30min before the insults with 200μM 6-OHDA. The cells were incubated for 24h. Cell viability and cells death were assessed by (3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide) MTT assay and lactate dehydrogenase (LDH) assay kit, respectively. AST-IV and CG inhibited the apoptosis of PC12 induced by 6-OHDA at 0.001 and 0.0001μM concentrations. On the basis of these results, we propose AST-IV and CG as potential neuroprotective agents in the treatment of Parkinson's disease.|