guggulsterone

{{Chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 414627051

| ImageFile1 = Guggulsterone E.png

| ImageSize1 = 200px

| ImageCaption1 = E-Guggulsterone

| ImageFile2 = Guggulsterone Z.png

| ImageSize2 = 200px

| ImageCaption2 = Z-Guggulsterone

| IUPACName = (8R,9S,10R,13S,14S)-17-Ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione

| OtherNames = Pregna-4,17-diene-3,16-dione

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 2745

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 95975-55-6

| CASNo1_Ref = {{cascite|correct|CAS}}

| CASNo1 = 39025-24-6

| CASNo1_Comment = (E)

| CASNo2_Ref = {{cascite|correct|CAS}}

| CASNo2 = 39025-23-5

| CASNo2_Comment = (Z)

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = A4PW148END

| UNII1_Ref = {{fdacite|correct|FDA}}

| UNII1 = 9B259YE66O

| UNII1_Comment = (E)

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 6CST3U34GN

| UNII2_Comment = (Z)

| PubChem = 6439929

| PubChem_Comment = (E)

| PubChem2 = 6450278

| PubChem2_Comment = (Z)

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 410683

| SMILES = O=C1C[C@@]2([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])CC[C@]2(C)/C1=C\C)=O

| SMILES_Comment = (E)

| SMILES1 = O=C1C[C@@]2([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])CC[C@]2(C)/C1=C/C)=O

| SMILES1_Comment = (Z)

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 4944297

| ChemSpiderID_Comment = (E)

| ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID1 = 4952892

| ChemSpiderID1_Comment = (Z)

| 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/b16-4-/t15-,17+,18+,20+,21-/m1/s1

| InChI_Comment = (E)

| InChIKey = WDXRGPWQVHZTQJ-AUKWTSKRSA-N

| InChI1 = 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/b16-4+/t15-,17+,18+,20+,21-/m1/s1

| InChI1_Comment = (Z)

| InChIKey1 = WDXRGPWQVHZTQJ-OSJVMJFVSA-N

}}

|Section2={{Chembox Properties

| C=21 | H=28 | O=2

| Appearance =

| Density =

| MeltingPt =

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|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

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}}

Guggulsterone is a phytosteroid found in the resin of the guggul plant, Commiphora mukul. Guggulsterone can exist as either of two stereoisomers, E-guggulsterone and Z-guggulsterone. In humans, it acts as an antagonist of the farnesoid X receptor, which was once believed to result in decreased cholesterol synthesis in the liver. Several studies have been published that indicate no overall reduction in total cholesterol occurs using various dosages of guggulsterone, and levels of low-density lipoprotein ("bad cholesterol") increased in many people.{{cite journal | title = Guggulipid Ineffective for Lowering Cholesterol | journal = JAMA | year = 2003 | volume = 290 | pages = 765–772 | pmid = 12915429 | last1 = Szapary | first1 = PO | last2 = Wolfe | first2 = ML | last3 = Bloedon | first3 = LT | last4 = Cucchiara | first4 = AJ | last5 = Dermarderosian | first5 = AH | last6 = Cirigliano | first6 = MD | last7 = Rader | first7 = DJ | issue = 6 | doi = 10.1001/jama.290.6.765| doi-access = }}{{cite journal | title = Guggulipid Use in Hyperlipidemia | journal = Am J Health-Syst Pharm | year = 2005 | volume = 62 | issue = 16 | pages = 1690–1692 | pmid = 16085931 | last1 = Sahni | first1 = S | last2 = Hepfinger | first2 = CA | last3 = Sauer | first3 = KA | doi = 10.2146/ajhp040580}} Nevertheless, guggulsterone is an ingredient in many nutritional supplements. Guggulsterone was also found to have interactions with the viral ADP ribose phosphatase enzyme of SARS-CoV-2 and has been proposed as a potential candidate for the development of therapeutics for the treatment of COVID-19.{{cite journal|vauthors=Kciuk M, Mujwar S, Rani I, Munjal K, Gielecińska A, Kontek R, Shah K|title=Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2|journal=Molecules|year=2022|volume=27|issue=23|page=8287 |id=Art. No. 8287|doi=10.3390/molecules27238287|doi-access=free|pmid=36500379|pmc=9739500}}

Guggulsterone is a broad-spectrum ligand of steroid hormone receptors, and is known to possess the following activities:{{cite journal|last1=Burris|first1=T. P.|title=The Hypolipidemic Natural Product Guggulsterone Is a Promiscuous Steroid Receptor Ligand|journal=Molecular Pharmacology|volume=67|issue=3|year=2004|pages=948–954|issn=0026-895X|doi=10.1124/mol.104.007054|pmid=15602004|s2cid=309272}}{{cite journal|last1=Brobst|first1=D. E.|title=Guggulsterone Activates Multiple Nuclear Receptors and Induces CYP3A Gene Expression through the Pregnane X Receptor|journal=Journal of Pharmacology and Experimental Therapeutics|volume=310|issue=2|year=2004|pages=528–535|issn=0022-3565|doi=10.1124/jpet.103.064329|pmid=15075359|s2cid=7093631}}{{cite book|author1=Hugo Kubinyi|author2=Gerhard Müller|title=Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective|url=https://books.google.com/books?id=oxvYXJSCImUC&pg=PA394|date=6 March 2006|publisher=John Wiley & Sons|isbn=978-3-527-60402-9|pages=394–}}{{cite book|author1=Roger Blumenthal|author2=JoAnne Foody|author3=Nathan D. Wong|title=Preventive Cardiology: A Companion to Braunwald's Heart Disease|url=https://books.google.com/books?id=pca-q0IoukIC&pg=PT1563|date=25 February 2011|publisher=Elsevier Health Sciences|isbn=978-1-4377-3785-1|pages=1563–}}

• Mineralocorticoid receptor antagonist (K_i = 39 nM)
• Progesterone receptor partial agonist (K_i = 201 nM)
• Glucocorticoid receptor antagonist (K_i = 224 nM)
• Androgen receptor antagonist (K_i = 240 nM)
• Estrogen receptor agonist (K_i > 5 μM; EC₅₀ > 5 μM)
• Farnesoid X receptor antagonist (IC₅₀ = 5–50 μM)
• Pregnane X receptor agonist (EC₅₀ = 2.4 μM ((Z)-isomer))

Guggulsterone has been found in animal research to be orally active; it has an absolute bioavailability of 42.9% after oral administration in rats, with a half-life of around 10 hours in this species, indicating a good pharmacokinetic profile.{{cite journal|last1=Verma|first1=N.|last2=Singh|first2=S.K.|last3=Gupta|first3=R.C.|title=Pharmacokinetics of Guggulsterone after Intravenous and Oral Administration in Rats|journal=Pharmacy and Pharmacology Communications|volume=5|issue=5|year=1999|pages=349–354|issn=1460-8081|doi=10.1211/146080899128734956|doi-broken-date=2024-11-11 }}