Isosteviol

CAS# 27975-19-5

Isosteviol

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Quality Control of Isosteviol

Number of papers citing our products

Chemical structure

Isosteviol

3D structure

Chemical Properties of Isosteviol

Cas No. 27975-19-5 SDF Download SDF
PubChem ID 314424 Appearance White powder
Formula C20H30O3 M.Wt 318.45
Type of Compound Diterpenoids Storage Desiccate at -20°C
Synonyms (-)-Isosteviol; iso-Steviol
Solubility DMSO : ≥ 100 mg/mL (314.02 mM)
*"≥" means soluble, but saturation unknown.
SMILES CC12CCC3C4(CCCC(C4CCC3(C1)CC2=O)(C)C(=O)O)C
Standard InChIKey KFVUFODCZDRVSS-UHFFFAOYSA-N
Standard InChI InChI=1S/C20H30O3/c1-17-9-5-14-18(2)7-4-8-19(3,16(22)23)13(18)6-10-20(14,12-17)11-15(17)21/h13-14H,4-12H2,1-3H3,(H,22,23)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Source of Isosteviol

The herbs of Stevia rebaudiana

Biological Activity of Isosteviol

DescriptionIsosteviol possesses various biological activities including anti-hyperglycemic, anti-hypertensive, anti-tumor, anti-inflammatory, neuroprotective, antibacterial, antifungal,and antioxidant effects.Isosteviol plays a protective role in a variety of stress-induced cardiac diseases, it can prevent the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.
Targetsp53 | PPAR | LDL | Antifection
In vitro

Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol.[Pubmed: 24444475]

Bioorg Med Chem Lett. 2014 Feb 15;24(4):1184-7.

Lung cancer is one of the most common malignancies worldwide.
METHODS AND RESULTS:
In this Letter, novel MOM-ether analogs of Isosteviol were designed and synthesized to be tested for anticancer activities against H1299 lung cancer cell lines. The effects of these derivatives were studied in H1299 human large cell lung carcinoma cells that are null for p53 and compared to normal counterparts NL-20 normal lung epithelial cells. The initial screening of twelve MOM-ether analogs of Isosteviol derivatives on H1299 lung cancer cells by MTT assay revealed that two derivatives (an ester and a carbamate) were the most potent in reducing cell viability. The IC50 values for these derivatives were determined to be 14 and 21 μM respectively. We compared the cytotoxicity of the best derivatives in H1299 lung cancer cells and NL-20 normal lung epithelial cells.
CONCLUSIONS:
Both derivatives showed lower cytotoxic effects on NL-20 normal lung epithelial cells. Moreover, both derivatives induced apoptosis in H1299 lung cancer cells more than NL-20 normal lung epithelial cells.

In Vitro Antibacterial, Antifungal, Antibiofilm, Antioxidant, and Anticancer Properties of Isosteviol Isolated from Endangered Medicinal Plant Pittosporum tetraspermum.[Pubmed: 26101532 ]

Evid Based Complement Alternat Med. 2015;2015:164261.

This study aimed to investigate the in vitro antibacterial, antifungal, antibiofilm, antioxidant, and anticancer properties of Isosteviol isolated from endangered medicinal plant Pittosporum tetraspermum.
METHODS AND RESULTS:
Pure compound was obtained and characterized by column chromatography followed by (1)H NMR, (13)C NMR, IR, and mass spectral analysis. The antimicrobial activities of the compound were assessed by the broth microdilution method and the antioxidant properties were determined using reducing ability assay, DPPH scavenging assay, hydroxyl radical scavenging activity, and superoxide radical scavenging assay. Anticancer study was evaluated by following MTT assay. Column purification and spectrocopical analysis lead to identifying Isosteviol from the crude ethyl acetate extract. The compound exhibited significant activity against bacteria such as Staphylococcus epidermidis (125 μg/mL), Staphylococcus aureus (125 μg/mL), and Klebsiella pneumoniae (62.5 μg/mL). The MIC of the compound against Candida albicans, Aspergillus niger, and Trichophyton mentagrophytes was 62.5, 125, and 500 μg/mL, respectively. The compound showed comparatively better antibiofilm activity against E. coli, S. typhi, and P. aeruginosa. Furthermore, it exhibited good antioxidant properties. Anticancer properties of the compound against Vero and MCF7 cell lines were its advantage.
CONCLUSIONS:
Novel Isosteviol would be useful to reduce the infectious diseases caused by pathogenic microorganisms or slow the progress of various oxidative stress-related diseases.

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.[Pubmed: 28428073 ]

Biochim Biophys Acta. 2017 Apr 18;1859(10):1872-1879.

Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of Ito is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases.
METHODS AND RESULTS:
Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells.
CONCLUSIONS:
The decrease and increase of current densities for Ito and ICaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of Ito and ICaL are correlated to the alterations of the mRNA transcription level.

In vivo

Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats.[Pubmed: 27047634 ]

Oxid Med Cell Longev. 2016;2016:1379162.

Previous report has indicated that Isosteviol has neuroprotective effects. However, Isosteviol was administered preventively before ischemia and the inclusion criteria were limited.
METHODS AND RESULTS:
In the present study, a more soluble and injectable form of Isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg·kg(-1) can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group.
CONCLUSIONS:
All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury.

Protocol of Isosteviol

Cell Research

Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.[Pubmed: 23418165]

Chem Biodivers. 2013 Feb;10(2):177-88.

Seventeen steviol derivatives, i.e., 2-18, and 19 Isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1).
METHODS AND RESULTS:
Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five Isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 μM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.
CONCLUSIONS:
These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.

Animal Research

The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion.[Pubmed: 22075495]

Life Sci. 2012 Jan 2;90(1-2):30-8.

The aim of present study was to investigate the effects of Isosteviol on hyperglycemia and hyperlipidemia in rats fed with high-fat emulsion (HFE). The effect of the supplement of palmitate in HFE on the activity of Isosteviol was investigated. Ultrastructural changes in islet β-cells and peroxisome proliferator-activated receptor α (PPARα) mRNA expression profile were determined.
METHODS AND RESULTS:
FSG, FSI, TC and LDL levels and insulin resistance index (IRI) were decreased and HDL level was increased by all doses of Isosteviol. During IVGTT, serum glucose levels were decreased by Isosteviol and no significant differences were observed in insulin release between Isosteviol-treated and control groups. The effects of Isosteviol were attenuated by palmitate. Damage to pancreatic islet cells was partially attenuated, and expression profile of hepatic PPARα mRNA was enhanced by Isosteviol.
CONCLUSIONS:
Antihyperglycemic effects of Isosteviol could enhance utilization of glucose in the periphery and reduce β-cell damage induced by dyslipidemia. Modulating-lipidemic effects of Isosteviol might be related to the potential enhancement of liver PPARα mRNA expression.

Isosteviol Dilution Calculator

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Preparing Stock Solutions of Isosteviol

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.1402 mL 15.7011 mL 31.4021 mL 62.8042 mL 78.5053 mL
5 mM 0.628 mL 3.1402 mL 6.2804 mL 12.5608 mL 15.7011 mL
10 mM 0.314 mL 1.5701 mL 3.1402 mL 6.2804 mL 7.8505 mL
50 mM 0.0628 mL 0.314 mL 0.628 mL 1.2561 mL 1.5701 mL
100 mM 0.0314 mL 0.157 mL 0.314 mL 0.628 mL 0.7851 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

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Background on Isosteviol

Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil. Target: Isosteviol dose-dependently relaxed the vasopressin (10-8 M)-induced vasoconstriction in isolated aortic rings with or without endothelium. However, in the presence of potassium chloride (3×10-2 M), the vasodilator effect of isosteviol on arterial strips disappeared. Only the inhibitors specific for the ATP-sensitive potassium (KATP) channel or small conductance calcium-activated potassium (SKCa) channel inhibited the vasodilator effect of isosteviol in isolated aortic rings contracted with 10-8 M vasopressin [1]. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca (2+)]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca (2+)]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present [2]. Isosteviol (1-100 micromol/l) inhibits angiotensin-II-induced DNA synthesis and endothelin-1 secretion. Measurements of 2'7'-dichlorofluorescin diacetate, a redox-sensitive fluorescent dye, showed an isosteviol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II [3].

References:
[1]. Wong KL, et al. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci. 2004 Mar 26;74(19):2379-87. [2]. Wong KL, et al. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med. 2004 Feb;70(2):108-12. [3]. Wong KL, et al. Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology. 2006;76(4):163-9.

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References on Isosteviol

Synthesis and cytotoxic activity of MOM-ether analogs of isosteviol.[Pubmed:24444475]

Bioorg Med Chem Lett. 2014 Feb 15;24(4):1184-7.

Lung cancer is one of the most common malignancies worldwide. In this Letter, novel MOM-ether analogs of Isosteviol were designed and synthesized to be tested for anticancer activities against H1299 lung cancer cell lines. The effects of these derivatives were studied in H1299 human large cell lung carcinoma cells that are null for p53 and compared to normal counterparts NL-20 normal lung epithelial cells. The initial screening of twelve MOM-ether analogs of Isosteviol derivatives on H1299 lung cancer cells by MTT assay revealed that two derivatives (an ester and a carbamate) were the most potent in reducing cell viability. The IC50 values for these derivatives were determined to be 14 and 21 muM respectively. We compared the cytotoxicity of the best derivatives in H1299 lung cancer cells and NL-20 normal lung epithelial cells. Both derivatives showed lower cytotoxic effects on NL-20 normal lung epithelial cells. Moreover, both derivatives induced apoptosis in H1299 lung cancer cells more than NL-20 normal lung epithelial cells.

Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.[Pubmed:23418165]

Chem Biodivers. 2013 Feb;10(2):177-88.

Seventeen steviol derivatives, i.e., 2-18, and 19 Isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five Isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 muM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.

Neuroprotective Effects of Isosteviol Sodium Injection on Acute Focal Cerebral Ischemia in Rats.[Pubmed:27047634]

Oxid Med Cell Longev. 2016;2016:1379162.

Previous report has indicated that Isosteviol has neuroprotective effects. However, Isosteviol was administered preventively before ischemia and the inclusion criteria were limited. In the present study, a more soluble and injectable form of Isosteviol sodium (STVNA) was administered intravenously hours after transient or permanent middle cerebral artery occlusion (tMCAO or pMCAO) to investigate its neuroprotective effects in rats. The rats were assessed for neurobehavioral deficits 24 hours after ischemia and sacrificed for infarct volume quantification and histology evaluation. STVNA 10 mg.kg(-1) can significantly reduce the infarct volumes compared with vehicle in animals subjected to tMCAO and is twice as potent as previously reported. Additionally, the therapeutic window study showed that STVNA could reduce the infarct volume compared with the vehicle group when administered 4 hours after reperfusion. A similar effect was also observed in animals treated 4 hours after pMCAO. Assessment of neurobehavioral deficits after 24 hours showed that STVNA treatment significantly reduced neurobehavioral impairments. The number of restored NeuN-labeled neurons was increased and the number of TUNEL positive cells was reduced in animals that received STVNA treatment compared with vehicle group. All of these findings suggest that STVNA might provide therapeutic benefits against cerebral ischemia-induced injury.

In Vitro Antibacterial, Antifungal, Antibiofilm, Antioxidant, and Anticancer Properties of Isosteviol Isolated from Endangered Medicinal Plant Pittosporum tetraspermum.[Pubmed:26101532]

Evid Based Complement Alternat Med. 2015;2015:164261.

This study aimed to investigate the in vitro antibacterial, antifungal, antibiofilm, antioxidant, and anticancer properties of Isosteviol isolated from endangered medicinal plant Pittosporum tetraspermum. Pure compound was obtained and characterized by column chromatography followed by (1)H NMR, (13)C NMR, IR, and mass spectral analysis. The antimicrobial activities of the compound were assessed by the broth microdilution method and the antioxidant properties were determined using reducing ability assay, DPPH scavenging assay, hydroxyl radical scavenging activity, and superoxide radical scavenging assay. Anticancer study was evaluated by following MTT assay. Column purification and spectrocopical analysis lead to identifying Isosteviol from the crude ethyl acetate extract. The compound exhibited significant activity against bacteria such as Staphylococcus epidermidis (125 microg/mL), Staphylococcus aureus (125 microg/mL), and Klebsiella pneumoniae (62.5 microg/mL). The MIC of the compound against Candida albicans, Aspergillus niger, and Trichophyton mentagrophytes was 62.5, 125, and 500 microg/mL, respectively. The compound showed comparatively better antibiofilm activity against E. coli, S. typhi, and P. aeruginosa. Furthermore, it exhibited good antioxidant properties. Anticancer properties of the compound against Vero and MCF7 cell lines were its advantage. Novel Isosteviol would be useful to reduce the infectious diseases caused by pathogenic microorganisms or slow the progress of various oxidative stress-related diseases.

Isosteviol prevents the prolongation of action potential in hypertrophied cardiomyoctyes by regulating transient outward potassium and L-type calcium channels.[Pubmed:28428073]

Biochim Biophys Acta Biomembr. 2017 Oct;1859(10):1872-1879.

Cardiac hypertrophy is a thickening of the heart muscle that is associated with cardiovascular diseases such as hypertension and myocardial infarction. It occurs initially as an adaptive process against increased workloads and often leads to sudden arrhythmic deaths. Studies suggest that the lethal arrhythmia is attributed to hypertrophy-induced destabilization of cardiac electrical activity, especially the prolongation of the action potential. The reduced activity of Ito is demonstrated to be responsible for the ionic mechanism of prolonged action potential duration and arrhythmogeneity. Isosteviol (STV), a derivative of stevioside, plays a protective role in a variety of stress-induced cardiac diseases. Here we report effects of STV on rat ISO-induced hypertrophic cardiomyocytes. STV alleviated ISO-induced hypertrophy of cardiomyocytes by decreasing cell area of hypertrophied cardiomyocytes. STV application prevented the prolongation of action potential which was prominent in hypertrophied cells. The decrease and increase of current densities for Ito and ICaL observed in hypertrophied myocytes were both prevented by STV application. In addition, the results of qRT-PCR suggested that the changes of electrophysiological activity of Ito and ICaL are correlated to the alterations of the mRNA transcription level.

The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion.[Pubmed:22075495]

Life Sci. 2012 Jan 2;90(1-2):30-8.

AIMS: The aim of present study was to investigate the effects of Isosteviol on hyperglycemia and hyperlipidemia in rats fed with high-fat emulsion (HFE). MAIN METHODS: Hyperglycemia and hyperlipidemia in rats was induced by daily ingestion of HFE for 14 days. Isosteviol (0.2, 1.0, or 5.0mg/kg/day) was orally administered for 7 days, with rosiglitazone maleate (5.0mg/kg/day) used as the positive control. The levels of fasting serum glucose (FSG), fasting serum insulin (FSI), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL) in serum were assayed. Intravenous glucose tolerance test (IVGTT) was performed with serum glucose and insulin levels monitored. The effect of the supplement of palmitate in HFE on the activity of Isosteviol was investigated. Ultrastructural changes in islet beta-cells and peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA expression profile were determined. KEY FINDINGS: FSG, FSI, TC and LDL levels and insulin resistance index (IRI) were decreased and HDL level was increased by all doses of Isosteviol. During IVGTT, serum glucose levels were decreased by Isosteviol and no significant differences were observed in insulin release between Isosteviol-treated and control groups. The effects of Isosteviol were attenuated by palmitate. Damage to pancreatic islet cells was partially attenuated, and expression profile of hepatic PPARalpha mRNA was enhanced by Isosteviol. SIGNIFICANCE: Antihyperglycemic effects of Isosteviol could enhance utilization of glucose in the periphery and reduce beta-cell damage induced by dyslipidemia. Modulating-lipidemic effects of Isosteviol might be related to the potential enhancement of liver PPARalpha mRNA expression.

Description

Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil.

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