| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
JNK; Akt; FXR; Caspase
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| ln Vitro |
GugguLsterone (0.5 -20 μM; 24 hours) suppresses the production of TREM-1, TLR4 and TNF-α and the phosphorylation of IκBα and NF-κB p65 by LPS [2].
Guggulsterone suppressed LX-2 cell growth in a dose- and activation-dependent manner. This growth suppression was due to the induction of HSC apoptosis, which was mediated by the activation of c-Jun N-terminal kinase and mitochondrial apoptotic signaling. Additionally, guggulsterone regulated phosphorylation of Akt and adenosine monophosphate-activated protein kinase, which were subsequently proven responsible for the guggulsterone-induced HSC growth suppression. Guggulsterone inhibited NF-κB activation in LX-2 cells, which is one of the major mediators in HSC activation. Indeed, guggulsterone decreased collagen α1 synthesis and α-smooth muscle actin expression in these cells. [3] |
| ln Vivo |
GugguLsterone (mouse; 100 mg/kg once daily for 8 days) significantly increased the incidence of TNBS-induced cystitis in wild-type mice [2].
Compared with the control mice or mice treated with a low dose of guggulsterone , high dose of guggulsterone significantly decreased the extent of collagen deposition and the percentage of activated HSCs undergoing apoptosis. Conclusions: These results demonstrate that guggulsterone suppressed HSC activation and survival by inhibiting NF-κB activation and inducing apoptosis. Therefore, guggulsterone may be useful as an antifibrotic agent in chronic liver diseases.[3] |
| Enzyme Assay |
Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-κB, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed M1 polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hyperactivation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD. NEW & NOTEWORTHY We found that guggulsterone attenuates triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated hyperactivation of macrophages and polarizes macrophages toward the M2 phenotype. This was mediated by IL-10 and partly Toll-like receptor 4 signaling pathways. Overall, these data support that guggulsterone as a natural plant sterol modulates macrophage phenotypes in colitis, which may be of novel therapeutic importance in inflammatory bowel disease treatment[2].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: RAW 264.7 murine macrophage Tested Concentrations: 0.5, 5, 10, 20 μM Incubation Duration: 24 hrs (hours) Experimental Results: LPS inhibits TREM-1, TLR4 and TNF-α expression as well as IκBα and NF-κB Phosphorylation of p65. |
| Animal Protocol |
Animal/Disease Models: TNBS-induced colitis in wild-type mice [2]
Doses: 100 mg/kg Route of Administration: po (po (oral gavage)) one time/day; for 8 days Experimental Results: Improved survival of wild-type mice with TNBS-induced colitis Rate. Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, which is characterized by steatosis, inflammation, and fibrosis. The aim of this designed study is to evaluate the ability of guggulsterone to prevent high fat diet induced steatohepatitis in mice. Five groups of male mice were selected and treated as the following: group I, mice had free access to standard commercial diet and considered as control group, group II, mice were fed a specially formulated high-fat diet for 12 weeks to induce non-alcoholic liver disease, while groups III, IV and V the mice were administered high fat diet containing guggulsterone at 500, 1000 and 2000 ppm concentration respectively for 12 weeks. Maintaining mice on fat rich diet only resulted in inducing the metabolic and histological changes related to NAFLD. While the treatment with guggulsterone significantly improves the evaluated markers. These results demonstrate guggulsterone may be useful in preventing the development of steatohepatitis.[4] |
| References |
[1]. Shishodia S, et al. Guggulsterone for Chemoprevention of Cancer. Curr Pharm Des. 2016;22(3):294-306.
[2]. Che X, et al. Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages. Am J Physiol Gastrointest Liver Physiol. 2018 Jul 1;315(1):G128-G139. [3]. Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis. J Gastroenterol Hepatol. 2013 Dec;28(12):1859-68. [4]. Possible Amelioration of the Severity of Nutritional Steatohepatitis by Guggulsterone in Mice. Iraqi J Pharm Sci, Vol.28(1) 2019. DOI: https://doi.org/10.31351/vol28iss1pp17-23; https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/801; https://pdfs.semanticscholar.org/fed5/b2b899b009d9a009406450b1d111bb67f233.pdf |
| Additional Infomation |
Guggulsterone is a 3-hydroxy steroid. It has a role as an androgen.
Guggulsterone has been reported in Commiphora mukul and Commiphora wightii with data available. |
| Molecular Formula |
C21H28O2
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|---|---|
| Molecular Weight |
312.4458
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| Exact Mass |
312.208
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| Elemental Analysis |
C, 80.73; H, 9.03; O, 10.24
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| CAS # |
95975-55-6
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| Related CAS # |
39025-23-5 (Z-Guggulsterone); 39025-24-6 (E-Guggulsterone)
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| PubChem CID |
6450278
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| Appearance |
Typically exists as White to off-white solids at room temperature
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
463.3±45.0 °C at 760 mmHg
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| Flash Point |
172.3±25.7 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.557
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| Source |
Commiphora wightii
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| LogP |
3.65
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
23
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| Complexity |
640
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C[C@@]12C(=CC)C(=O)C[C@H]1[C@@H]1CCC3=CC(CC[C@]3(C)[C@H]1CC2)=O
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| InChi Key |
WDXRGPWQVHZTQJ-BVEOMGIMSA-N
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| InChi Code |
InChI=1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/t15?,17?,18?,20-,21+/m0/s1
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| Chemical Name |
(10R,13S)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione
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| Synonyms |
Z/E-Guggulsterone; Guggulsterone; 95975-55-6; (10R,13S)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~20.83 mg/mL (~66.67 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.25 mg/mL (4.00 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (4.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 10 mg/mL (32.01 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2005 mL | 16.0026 mL | 32.0051 mL | |
| 5 mM | 0.6401 mL | 3.2005 mL | 6.4010 mL | |
| 10 mM | 0.3201 mL | 1.6003 mL | 3.2005 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01492998 | Terminated | Other: guggulsterone, a natural FXR antagonist. | Chronic Hepatitis C | Hospices Civils de Lyon | 2010-01 | Not Applicable |
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