The Hypolipidemic Natural Product Guggulsterone Is a Promiscuous Steroid Receptor Ligand

Burris, Thomas P.; Montrose, Chahrzad; Houck, Keith A.; Osborne, Harold E.; Bocchinfuso, Wayne P.; Yaden, Benjamin C.; Cheng, Christine; Zink, Richard W.; Barr, R. J.; Hepler, Christopher D; Krishnan, Venkatesh; Bullock, Heather A; Burris, Lorri L; Galvin, Rachelle J. Sells; Bramlett, Kelli; Stayrook, Keith R.

doi:10.1124/mol.104.007054

Cited by 115 publications

(81 citation statements)

References 33 publications

(40 reference statements)

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“…Still, another possibility is the prevention of cholesterol synthesis in the liver by ketogenic steroids [8,10]. Guggulsterones E and Z are effective antagonists of the bile acids receptor, farnesoid X receptor, which is primarily expressed in the liver, kidney, and small intestine; it regulates the expression of genes involved in cholesterol/bile acids homeostasis, allowing more cholesterol catabolism and excretion from the body [10]. Studies of the efficacy of guggul for hypercholesterolemia have produced conflicting results and information currently available indicates that guggul may be effective for lowering total cholesterol and TG in patients on a non-Western diet [11].…”

Section: Shaik and Khanmentioning

confidence: 99%

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Antihyperlipidemic Activity of Commiphora Mukul Against Atherogenic Diet-Induced Hyperlipidemia in Experimental Rats

Shaik

Khan

2018

Asian J Pharm Clin Res

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Objective: The aim of the present study was to investigate the effect of antihyperlipidemic activity of ethyl acetate extract of Commiphora mukul (EECM) gum resin and compares its efficacy with that of atorvastatin against atherogenic diet-induced hyperlipidemia model using rat as an experimental animal.Methods: Wistar albino rats were divided into five groups. Control animals received normal diet, hyperlipidemic control; rats treated with EECM 100 and 200 mg/kg and positive control, receiving standard drug atorvastatin 2.70 mg/kg. Results:Increase the level of serum cholesterol, phospholipids, high-density lipoproteins, low-density lipoproteins, and triglycerides causing hyperlipidemia further leading to the development of atherosclerosis. On the other hand, oral administration of ethyl acetate extract of C. mukul at dose of 200 mg/kg for 15 days resulted in the prevention of above abnormalities. Conclusion:The results suggest that EECM could be beneficial in the treatment of atherosclerosis, characterized by atherogenic lipoprotein profile and abnormalities in lipid metabolism.

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Section: Shaik and Khanmentioning

confidence: 99%

“…HDL concentration was significantly increased on C. mukul extract treatment in this present investigation. The observed hypolipidemic activity of EECM may be due to the presence of plant sterols (guggulsterone E and guggulsterone) [8][9][10][11]19].…”

Section: Shaik and Khanmentioning

confidence: 99%

Antihyperlipidemic Activity of Commiphora Mukul Against Atherogenic Diet-Induced Hyperlipidemia in Experimental Rats

Shaik

Khan

2018

Asian J Pharm Clin Res

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“…HuH7 and HEK293 cells were seeded in 96-well plates at 25,000 cells per well as described 58 with the modifications outlined in the Supplementary Methods.…”

Section: Co-transfection and Reporter Assaysmentioning

confidence: 99%

Identification of heme as the ligand for the orphan nuclear receptors REV-ERBα and REV-ERBβ

Raghuram

Stayrook

Huang

et al. 2007

Nat Struct Mol Biol

510

509

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The nuclear receptors REV-ERBα (encoded by NR1D1) and REV-ERBβ (NR1D2) have remained orphans owing to the lack of identified physiological ligands. Here we show that heme is a physiological ligand of both receptors. Heme associates with the ligand-binding domains of the REV-ERB receptors with a 1:1 stoichiometry and enhances the thermal stability of the proteins. Results from experiments of heme depletion in mammalian cells indicate that heme binding to REV-ERB causes the recruitment of the co-repressor NCoR, leading to repression of target genes including BMAL1 (official symbol ARNTL), an essential component of the circadian oscillator. Heme extends the known types of ligands used by the human nuclear receptor family beyond the endocrine hormones and dietary lipids described so far. Our results further indicate that heme regulation of REV-ERBs may link the control of metabolism and the mammalian clock.REV-ERBα was originally identified as an orphan member of the nuclear hormone receptor (NHR) family on the basis of its canonical domain structure and sequence conservation 1,2 . REV-ERBβ was subsequently identified by its homology to other NHRs and its pattern of expression, which overlaps greatly with that of REV-ERBα. Both receptors have particularly high expression in the liver, adipose tissue, skeletal muscle and brain 3-8 , where they are transcribed in a circadian manner 9-11 . The REV-ERBs are unique in the NHR superfamily in that they lack the carboxy-terminal tail (helix 12) of the ligand-binding domain (LBD), which is required for coactivator recognition 12

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“…No obstante este aparente efecto negativo sobre los lípidos del plasma, este estudio no evaluó la eliminación fecal de sales biliares, la cual podría estar aumentada indicando un balance neto negativo del colesterol corporal. Por otro lado, se ha descrito que la gugulesterona es capaz de activar otros receptores nucleares, tales como el receptor de andrógenos, el receptor de glucocorticoides, el receptor de mineralocorticoides y el receptor de progesterona 50 , dificultando la interpretación de su efecto final en humanos. Por lo tanto, serán de gran interés los resultados que se obtengan con el uso de agonistas y antagonistas farmacológicos especí-ficos para este receptor nuclear.…”

Section: A R T í C U L Ounclassified

Nuevos receptores nucleares heterodiméricos: reguladores metabólicos con impacto en fisiopatología y su proyección terapéutica en dislipidemias y diabetes mellitus

Cortés¹,

Quezada²,

Rigotti

et al. 2005

Rev. méd. Chile

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The Hypolipidemic Natural Product Guggulsterone Is a Promiscuous Steroid Receptor Ligand

Cited by 115 publications

References 33 publications

Antihyperlipidemic Activity of Commiphora Mukul Against Atherogenic Diet-Induced Hyperlipidemia in Experimental Rats

Antihyperlipidemic Activity of Commiphora Mukul Against Atherogenic Diet-Induced Hyperlipidemia in Experimental Rats

Identification of heme as the ligand for the orphan nuclear receptors REV-ERBα and REV-ERBβ

Nuevos receptores nucleares heterodiméricos: reguladores metabólicos con impacto en fisiopatología y su proyección terapéutica en dislipidemias y diabetes mellitus

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