Chenodeoxycholic acid

 Cat.No.£ºIC-015568

Product Information

Biological Activity

Chenodeoxycholic acid (CDCA) and Deoxycholic acid (DCA) both inhibit 11 beta HSD2 with IC₅₀ values of 22 mM and 38 mM, respectively and causes cortisol-dependent nuclear translocation and increases transcriptionalactivity of mineralocorticoid receptor (MR)^[1]. Chenodeoxycholic acid is able to stimulate Ishikawa cell growth by inducing a significant increase in Cyclin D1 protein and mRNA expression through the activation of the membrane G protein-coupled receptor (TGR5)-dependent pathway^[2]. Chenodeoxycholic acid (CDCA) induces LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold in a cultured human hepatoblastoma cell line, Hep G2^[3]. Chenodeoxycholic acid-induced Isc is inhibited (¡Ý67%) by Bumetanide, BaCl₂, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. Chenodeoxycholic acid-stimulated Isc is decreased 43% by the adenylate cyclase inhibitor MDL12330A and Chenodeoxycholic acid increases intracellular cAMP concentration^[4]. Chenodeoxycholic acid treatment activates C/EBP¦Â, as shown by increases in its phosphorylation, nuclear accumulation, and expression in HepG2 cells. Chenodeoxycholic acid enhances luciferase gene transcription from the construct containing -1.65-kb GSTA2 promoter, which contains C/EBP response element (pGL-1651). Chenodeoxycholic acid treatment activates AMP-activated protein kinase (AMPK), which leads to extracellular signal-regulated kinase 1/2 (ERK1/2) activation, as evidenced by the results of experiments using a dominant-negative mutant of AMPK¦Á and chemical inhibitor^[5].

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species

Mouse

Rat

Rabbit

Guinea pig

Hamster

Dog

Weight (kg)

0.02

0.15

1.8

0.4

0.08

10

Body Surface Area (m2)

0.007

0.025

0.15

0.05

0.02

0.5

Km factor

3

6

12

8

5

20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by  (Animal B Km / Animal A Km)
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

Molecular Weight

392.57

Formula

 C₂₄H₄₀O₄

CAS Number

Purity

>98%

Solubility

¡Ý 50 mg/mL (127.37 mM) in DMSO

Storage

at -20¡ãC

References Information

[1]. Stauffer AT, et al. Chenodeoxycholic acid and deoxycholic acid inhibit 11 beta-hydroxysteroid dehydrogenase type 2 and cause cortisol-induced transcriptional activation of the mineralocorticoid receptor. J Biol Chem. 2002 Jul 19;277(29):26286-92
[2]. Casaburi I, et al. Chenodeoxycholic acid through a TGR5-dependent CREB signaling activation enhances cyclin D1 expression and promotes human endometrial cancer cell proliferation. Cell Cycle. 2012 Jul 15;11(14):2699-710
[3]. Kawabe Y, et al. The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells. Biochem Biophys Res Commun. 1995 Mar 8;208(1):405-11.
[4]. Ao M, et al. Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells. Am J Physiol Cell Physiol. 2013 Aug 15;305(4):C447-56
[5]. Noh K, et al. Farnesoid X receptor activation by chenodeoxycholic acid induces detoxifying enzymes through AMP-activated protein kinase and extracellular signal-regulated kinase 1/2-mediated phosphorylation of CCAAT/enhancer binding protein ¦Â. Drug Metab