(E)-Guggulsterone
(Synonyms: 孕二烯二酮,(E)-Guggulsterone) 目录号 : GC46336
A farnesoid X receptor antagonist
Cas No.:39025-24-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1 They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3 Bile acid-
1.Makishima, M., Okamoto, A.Y., Repa, J.J., et al.Identification of a nuclear receptor for bile acidsScience2841362-1365(1999) 2.Barbier, O., Torra, I.P., Sirvent, A., et al.FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activityGastroenterology1241926-1940(2003) 3.Tan, K.P., Yang, M., and Ito, S.Activation of nuclear factor (erythroid-2 like) factor 2 by toxic bile acids provokes adaptive defense responses to enhance cell survival at the emergence of oxidative stressMol. Pharmacol.72(5)1380-1390(2007) 4.Urizar, N.L., Liverman, A.B., Dodds, D.T., et al.A natural product that lowers cholesterol as an anatagonist ligand for FXRScience296(5573)1703-1706(2002) 5.Cui, J., Huang, L., Zhao, A., et al.Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pumpThe Journal of Biological Chemisty278(12)10214-10220(2003) 6.Wu, J., Xia, C., Meier, J., et al.The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptorMolecular Endocrinology16(7)1590-1597(2002)
| Cas No. | 39025-24-6 | SDF | |
| 别名 | 孕二烯二酮,(E)-Guggulsterone | ||
| Canonical SMILES | O=C1CC[C@@]2(C)C(CC[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC(/C4=C\C)=O)=C1 | ||
| 分子式 | C21H28O2 | 分子量 | 312.5 |
| 溶解度 | DMF: 10 mg/ml,DMF:PBS (pH 7.2) (1:4): 0.2 mg/ml,DMSO: 0.25 mg/ml,Ethanol: 1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.2 mL | 16 mL | 32 mL |
| 5 mM | 0.64 mL | 3.2 mL | 6.4 mL |
| 10 mM | 0.32 mL | 1.6 mL | 3.2 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
(E)-Guggulsterone Inhibits Dengue Virus Replication by Upregulating Antiviral Interferon Responses through the Induction of Heme Oxygenase-1 Expression
Viruses 2021 Apr 20;13(4):712.PMID:33924157DOI:10.3390/v13040712.
Dengue virus (DENV) infection, which causes dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is a severe global health problem in tropical and subtropical areas. There is no effective vaccine or drug against DENV infection. Thus, the development of anti-DENV agents is imperative. This study aimed to assess the anti-DENV activity of (E)-Guggulsterone using a DENV infectious system. A specific inhibitor targeting signal molecules was used to evaluate the molecular mechanisms of action. Western blotting and qRT-PCR were used to determine DENV protein expression and RNA replication, respectively. Finally, an ICR suckling mouse model was used to examine the anti-DENV activity of (E)-Guggulsterone in vivo. A dose-dependent inhibitory effect of (E)-Guggulsterone on DENV protein synthesis and RNA replication without cytotoxicity was observed. The mechanistic studied revealed that (E)-Guggulsterone stimulates Nrf2-mediated heme oxygenase-1 (HO-1) expression, which increases the antiviral interferon responses and downstream antiviral gene expression by blocking DENV NS2B/3B protease activity. Moreover, (E)-Guggulsterone protected ICR suckling mice from life-threatening DENV infection. These results suggest that (E)-Guggulsterone can be a potential supplement for controlling DENV replication.
Binding studies of guggulsterone-E to calf thymus DNA by multi-spectroscopic, calorimetric and molecular docking studies
Spectrochim Acta A Mol Biomol Spectrosc 2018 Feb 5;190:402-408.PMID:28954252DOI:10.1016/j.saa.2017.09.065.
Guggulsterone, a sterol found in plants is used as an ayurvedic medicine for many diseases such as obesity, internal tumors, ulcers etc. E and Z are two isoforms of guggulsterone, wherein guggulsterone-E (GUGE) has also been shown to have anticancer potential. Most of the anticancer drugs target nucleic acids. Therefore, we studied the mode of interaction between ctDNA and GUGE using UV-Vis, fluorescence and CD spectroscopy, isothermal calorimetry along with molecular docking studies. Hoechst 3325, ethidium bromide and rhodamine-B displacement experiments confirms that GUGE binds in the minor groove of DNA. ITC results further suggest these interactions to be feasible and spontaneous with hydrogen bond formation and van der waals interactions. Lastly, molecular docking also suggests GUGE to be a minor groove binder interacting through a single hydrogen bond formation between OH group of GUGE and nitrogen (N3) of adenosine (A6).
HPTLC method for guggulsterone. I. Quantitative determination of E- and Z-guggulsterone in herbal extract and pharmaceutical dosage form
J Pharm Biomed Anal 2004 Sep 21;36(1):33-41.PMID:15351045DOI:10.1016/j.jpba.2004.04.014.
A sensitive, selective, precise and robust high-performance thin-layer chromatographic method of analysis of E and Z stereoisomers of guggulsterone (the hypolipidemic agent in the gum-resin exudates of Commiphora mukul) both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-acetone (9:1, v/v). Densitometric analysis of guggulsterone was carried out in the absorbance mode at 250 nm. This system was found to give compact spots for E- and Z-guggulsterone (Rf value of 0.38 +/- 0.02 and 0.46 +/- 0.02, respectively) following double development of chromatoplates with the same mobile phase. The linear regression analysis data for the calibration plots for E- and Z-guggulsterone showed good linear relationship with r2 = 0.9977 +/- 0.054 and 0.9975 +/- 0.068, respectively, in the concentration range of 100-6000 ng/spot. The mean value of slope and intercept were 0.11 +/- 0.006 and 0.11 +/- 0.005, 14.26 +/- 0.56 and 10.92 +/- 0.76, respectively, for E- and Z-guggulsterone. The method was validated for precision, robustness and recovery. The limit of detection and quantitation were 12, 10 and 24, 20 ng/spot, respectively, for E- and Z-guggulsterone. Statistical analysis proves that the method is repeatable and selective for the estimation of the said drug. Since the proposed mobile phase effectively resolves the E- and Z-isomers of guggulsterone, this HPTLC method can be applied for identification and quantitation of these isomers in herbal extracts and pharmaceutical dosage form.
CYP3A4 mediated pharmacokinetics drug interaction potential of Maha-Yogaraj Gugglu and E, Z guggulsterone
Sci Rep 2021 Jan 12;11(1):715.PMID:33436877DOI:10.1038/s41598-020-80595-5.
Maha yogaraja guggulu (MYG) is a classical herbomineral polyherbal formulation being widely used since centuries. The aim of this study was to investigate the effect of MYG formulation and its major constituents E & Z guggulsterone on CYP3A4 mediated metabolism. In vitro inhibition of MYG and Guggulsterone isomers on CYP3A4 was evaluated by high throughput fluorometric assay. Eighteen Adult male Sprague-Dawley rats (200 ± 25 g body weight) were randomly divided into three groups. Group A, Group B and Group C were treated with placebo, MYG and Standard E & Z guggulsterone for 14 days respectively by oral route. On 15th day, midazolam (5 mg/kg) was administered orally to all rats in each group. Blood samples (0.3 mL) were collected from the retro orbital vein at 0.25, 0.5, 0.75, 1, 2, 4, 6, 12 and 24 h of each rat were collected. The findings from the in vitro & in vivo study proposed that the MYG tablets and its guggulsterone isomers have drug interaction potential when consumed along with conventional drugs which are CYP3A4 substrates. In vivo pharmacokinetic drug interaction study of midazolam pointed out that the MYG tablets and guggulsterone isomers showed an inhibitory activity towards CYP3A4 which may have leads to clinically significant interactions.
Quantitative determination of guggulsterone in existing natural populations of Commiphora wightii (Arn.) Bhandari for identification of germplasm having higher guggulsterone content
Physiol Mol Biol Plants 2015 Jan;21(1):71-81.PMID:25648764DOI:10.1007/s12298-014-0271-1.
Guggulsterone is an aromatic steroidal ketonic compound obtained from vertical rein ducts and canals of bark of Commiphora wightii (Arn.) Bhandari (Family - Burseraceae). Owing to its multifarious medicinal and therapeutic values as well as its various other significant bioactivities, guggulsterone has high demand in pharmaceutical, perfumery and incense industries. More and more pharmaceutical and perfumery industries are showing interest in guggulsterone, therefore, there is a need for its quantitative determination in existing natural populations of C. wightii. Identification of elite germplasm having higher guggulsterone content can be multiplied through conventional or biotechnological means. In the present study an effort was made to estimate two isoforms of guggulsterone i.E. E and Z guggulsterone in raw exudates of 75 accessions of C. wightii collected from three states of North-western India viz. Rajasthan (19 districts), Haryana (4 districts) and Gujarat (3 districts). Extracted steroid rich fraction from stem samples was fractionated using reverse-phase preparative High Performance Liquid Chromatography (HPLC) coupled with UV/VIS detector operating at wavelength of 250 nm. HPLC analysis of stem samples of wild as well as cultivated plants showed that the concentration of E and Z isomers as well as total guggulsterone was highest in Rajasthan, as compared to Haryana and Gujarat states. Highest concentration of E guggulsterone (487.45 μg/g) and Z guggulsterone (487.68 μg/g) was found in samples collected from Devikot (Jaisalmer) and Palana (Bikaner) respectively, the two hyper-arid regions of Rajasthan, India. Quantitative assay was presented on the basis of calibration curve obtained from a mixture of standard E and Z guggulsterones with different validatory parameters including linearity, selectivity and specificity, accuracy, auto-injector, flow-rate, recoveries, limit of detection and limit of quantification (as per norms of International conference of Hormonization). Present findings revealed the role of environmental factors on biosynthesis of guggulsterone isomers under natural conditions.