Product name: Deoxycholic acid
Synonym name:
Catalogue No.: SBP03885
Cas No.: 83-44-3
Formula: C₂₄H₄₀O₄
Mol Weight: 392.58
Botanical Source:
Physical Description: White powder
Type of Compound: Steroids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of Deoxycholic acid

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Deoxycholic acid, as a secondary bile acid, is one of the key end products of cholesterol metabolism in the human and animal bodies. Its chemical essence is a derivative of bile acid, CAS number 83-44-3. For a long time, bile acids have been mainly regarded as "detergents" that promote lipid digestion and absorption. However, in the past two decades, with the deepening of molecular pharmacology research, the role of bile acids as an important signaling molecule has gradually been revealed. Deoxycholic acid is not only a byproduct of gut microbiota metabolism, but also a regulator of various physiological and pathological processes. It can specifically activate key receptors such as TGR5 (GPBAR1) and farnesol X receptors, thereby playing a core regulatory role in energy metabolism, glucose homeostasis, inflammatory response, and bile acid metabolism. Its traditional application in choleretic therapy has been interpreted by modern pharmacological targets, including ABCG5, FXR, TGR5, SLC10A2, and ABCB11. This article aims to systematically review the chemical properties, sources, pharmacological activities, molecular mechanisms of action, pharmacological characteristics, and potential application prospects of deoxycholic acid in disease treatment, in order to provide a comprehensive academic perspective for the deep development and clinical application of this natural product.

Chemical structure and physicochemical properties

The chemical name of deoxycholic acid is 3 α, 12 α - dihydroxy-5 β - cholic acid, with a molecular formula of C ₂₄ H ₄₀ O ₄ and a molecular weight of 392.5800. Its structural skeleton is the steroid parent nucleus (cyclopentane dihydrophenanthrene), which belongs to the 5 β - series of bile acids. Compared with primary bile acids such as bile acids, deoxycholic acid lacks one hydroxyl group at the C-7 position and only retains two alpha configured hydroxyl groups at the C-3 and C-12 positions. This structural difference significantly affects its physicochemical properties and biological activity.

It has strong hydrophobicity, with a calculated LogP value of about 3.95, indicating high lipid solubility. The theoretical polar surface area (TPSA) is 77.76 Å ². It has poor water solubility, approximately 0.0435 mg/mL, which is consistent with its hydrophobic steroid nucleus structure. At physiological pH, deoxycholic acid usually exists in the form of deprotonated bile acid salts, and the water solubility and surface activity of its sodium or potassium salt are significantly enhanced, which is the basis for its emulsifying fat function. The presence of carboxyl and hydroxyl groups in deoxycholic acid molecules enables them to form complexes with metal ions and has a certain acidity. Its crystals are usually white or off white powder. These physicochemical properties determine its distribution, metabolism, and patterns of interaction with targets in the body.

Plant sources and extraction methods

Strictly speaking, deoxycholic acid is not a typical natural product of plant origin, but mainly exists in the bile of vertebrates, especially in animals such as cows, sheep, and pigs with high bile content. In animal bodies, it is converted from primary bile acids (mainly bile acids) through 7 α - dehydroxylation by intestinal anaerobic bacteria (such as Clostridium bacteria). Therefore, commercial deoxycholic acid is mainly extracted from animal bile and is one of the active ingredients in animal medicinal materials such as bezoar and bear bile. It is also an important intermediate in the preparation of bile acid drugs.

The traditional extraction method is mainly based on the difference in solubility of bile acids in different solvents. The general process includes: 1) Raw material processing: collecting animal bile, concentrating and drying it to obtain bile paste or powder; 2) Saponification hydrolysis: Heating hydrolysis under alkaline conditions to hydrolyze bound bile acids (such as glycocholic acid, taurocholic acid, etc.) into free bile acids; 3) Acidic precipitation: Adjust the pH to acidity with inorganic acids to precipitate free bile acids; 4) Separation and purification: Using organic solvents (such as ethanol, acetone, ethyl acetate) for repeated extraction, crystallization, or column chromatography (such as silica gel column, reverse phase C18 column) to separate deoxycholic acid from other bile acids (such as cholic acid, chenodeoxycholic acid). Modern industrial production increasingly adopts efficient preparation chromatography, crystallization separation technology, as well as enzymatic or microbial transformation methods (using bile acid as a substrate and specific strains for 7 α - dehydroxylation) to obtain high-purity deoxycholic acid. These methods ensure a stable supply as research reagents and pharmaceutical raw materials.

Pharmacological activity research

Deoxycholic acid exhibits a wide and complex pharmacological activity, far exceeding its traditional digestive function.

1. Choleretic effect This is its classic pharmacological effect. Deoxycholic acid can directly stimulate liver cells to secrete bile rich in water and electrolytes, while promoting the function of transport proteins (such as ABCB11, the bile salt efflux pump) on the bile duct membrane, increasing bile acid dependent bile flow. It can also relax the Oddi sphincter and promote the discharge of bile into the duodenum.
2. Metabolic regulation effect Deoxycholic acid is an important metabolic regulatory signaling molecule. By activating TGR5 receptor, it can stimulate intestinal L cells to secrete glucagon like peptide-1, thereby promoting insulin secretion, improving insulin sensitivity, and inhibiting appetite, which has potential therapeutic significance for type 2 diabetes and obesity. In addition, by activating FXR, it can inhibit the expression of key hepatic gluconeogenesis enzymes and regulate glucose metabolism.
3. Anti inflammatory and immune regulatory effects Research has shown that deoxycholic acid can inhibit the activation of NLRP3 inflammasome in macrophages through the TGR5-cAMP PKA pathway, reduce the release of pro-inflammatory factors such as interleukin-1 β, and exert anti-inflammatory effects. It can also regulate intestinal barrier function, affect immune cell differentiation, and show protective effects in disease models such as inflammatory bowel disease and non-alcoholic fatty liver disease.
4. Cell protection and apoptosis regulation At low concentrations, deoxycholic acid may have a protective effect on liver cells by activating survival signaling pathways such as EGFR and MAPK. However, high concentrations of deoxycholic acid have cytotoxicity and can induce oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress, leading to cell apoptosis or necrosis. This concentration dependent dual effect is of great significance in the occurrence and development of cholestatic liver injury and colon cancer.
5. Regulation of gut microbiota As a metabolite of the microbiota, deoxycholic acid itself can shape the structure of the intestinal microbiota. Its strong antibacterial activity, especially against Gram positive bacteria, helps maintain the balance of gut microbiota, but excessive amounts may also lead to dysbiosis of the microbiota.

Mechanism of action and molecular targets

The pharmacological effects of deoxycholic acid are mainly mediated by acting on specific membrane receptors and nuclear receptors, with the following core targets:

1. G protein coupled receptor TGR5 (GPBAR1)This is a high affinity receptor for deoxycholic acid (EC ₅₀ at the micromolar level). After binding to TGR5, deoxycholic acid activates Gs protein, increases intracellular cAMP levels, and subsequently activates protein kinase A (PKA) and its downstream signals. This pathway is the main molecular basis for its regulation of energy metabolism (GLP-1 secretion), inhibition of macrophage inflammatory response, promotion of brown adipose tissue thermogenesis, and vasodilation.
2. Farnesol X receptor (FXR, NR1H4)FXR is a key nuclear receptor for bile acid homeostasis. Deoxycholic acid is a medium affinity ligand for FXR. The activated FXR forms a heterodimer with the retinol X receptor (RXR) and binds to the bile acid responsive element in the promoter region of the target gene, regulating gene transcription. Its choleretic effect is partially achieved through FXR: after FXR activation, ABCB11 (BSEP) and ABCC2 (MRP2) on the bile duct membrane are upregulated, promoting the excretion of bile acids and organic anions; Simultaneously inducing the expression of small intestine fibroblast growth factor 19 (FGF19, human derived FGF15), which inhibits the transcription of cholesterol 7 α - hydroxylase (CYP7A1) in the liver and negatively feedback inhibits de novo synthesis of bile acids.
3. Transporter protein target：
   • SLC10A2 (Top Sodium Dependent Bile Salt Transporter, ASBT）Located on the apical membrane of epithelial cells at the terminal ileum, responsible for the reabsorption of bile acids. Deoxycholic acid is one of its substrates and inhibitors, which can block enterohepatic circulation and promote bile acid excretion through competitive inhibition. It is used to treat cholestasis or hypercholesterolemia.
   • ABCB11（BSEP）The main bile acid efflux pump on the bile duct membrane of liver cells. Deoxycholic acid is not only its transport substrate, but also upregulates its expression through the FXR pathway, directly promoting bile secretion.
   • ABCG5/G8 A heterodimer transporter protein located in the bile duct membrane of liver cells and the apical membrane of intestinal epithelial cells, responsible for pumping cholesterol and plant sterols out of cells. Deoxycholic acid may indirectly affect its expression through pathways such as FXR and participate in cholesterol homeostasis regulation.

These targets form a complex network that enables deoxycholic acid to integrate and regulate bile acid metabolism, lipid metabolism, glucose homeostasis, and inflammatory response.

Evaluation of drug properties and pharmacokinetics

Based on the provided pharmacological parameters, deoxycholic acid exhibits the following characteristics:
* Molecular weight (392.58)Meets the general range of small molecule drugs (<500).
* Fat solubility (LogP~3.95)A higher LogP value indicates good membrane permeability, but may lead to poor water solubility (0.0435 mg/mL), affecting oral absorption and formulation development. Usually, it needs to be made in salt form (such as sodium salt) to improve bioavailability.
* Polar surface area (TPSA 77.76 Å ²)This value is at a moderate level and has a certain impact on membrane permeability, but it is not the main limiting factor.
* Blood-brain barrier permeability Predicted as' low ', which is consistent with most bile acid characteristics and has a lower risk of central nervous system side effects.
* Preliminary safety warning HERG inhibition is' no ', indicating a low risk of potential cardiac toxicity (inducing long QT syndrome). The Ames test result is 0.0, indicating no mutagenicity and low genetic toxicity risk in this testing system.

Pharmacokinetic aspects Deoxycholic acid is mainly actively absorbed through ASBT in the ileum after oral administration, with a high absorption rate. After absorption, it binds with albumin and enters the liver through the portal vein. In the liver, the majority (>90%) is rapidly taken up and combined with glycine or taurine to form conjugated deoxycholic acid, which is then secreted into bile and enters the enterohepatic circulation. A small amount enters the systemic circulation. In addition to binding reactions, its metabolism can also undergo differential isomerization and other transformations under the action of intestinal microbiota. Mainly excreted through feces (via bile), with a very small amount excreted through the kidneys. Its pharmacokinetics are significantly influenced by gut hepatic circulation, gut microbiota status, and liver function. As an endogenous substance, the immunogenicity risk of exogenous administration is extremely low.

Clinical application prospects and prospects

Deoxycholic acid currently has clear clinical applications and shows broad prospects for expansion.

1. Existing and traditional applications：

   • Choleretic drugs As a regulator of biliary function, it is used to treat conditions such as insufficient bile secretion and chronic cholecystitis.
   • Local fat solubilizer The US FDA has approved injection of deoxycholic acid (Kybella) ®/ Belkyra ®） Used to improve the accumulation of fat under the chin in adults (double chin). The mechanism is to induce adipocyte lysis by disrupting the adipocyte membrane.

2. Potential therapeutic areas：

   • Metabolic diseases Based on its powerful TGR5 agonist activity, the development of TGR5 agonists with higher selectivity and stable metabolism for the treatment of type 2 diabetes, obesity and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a current research hotspot. Deoxycholic acid and its structurally optimized derivatives are important lead compounds.
   • cholestatic liver diseases Through its choleretic and FXR activation properties, it may be used to improve the symptoms of bile stasis in diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The success of the FXR agonist obeticolic acid (6-ECDCA) partially validated this pathway.
   • Gastrointestinal diseases Its role in regulating gut microbiota, anti-inflammatory, and protecting the intestinal barrier makes it of exploratory value in the adjuvant treatment of Clostridium difficile infection and inflammatory bowel disease (IBD).
   • Cardiovascular and neuroprotection TGR5 activated vasodilation and antiatherosclerotic effects, as well as potential neuroanti-inflammatory effects, provide new ideas for related diseases.

3. Challenges and Prospects：

   • Duality and Dose Window Its concentration dependent dual effects of cell protection and toxicity require precise control of therapeutic concentration to avoid liver and intestinal toxicity.
   • Receptor selectivity Deoxycholic acid has activity on both FXR and TGR5, and its broad effects may bring unforeseen side effects. The future direction is to develop derivatives or formulations with higher receptor subtype selectivity or tissue targeting.
   • Microbial interference Long term systemic administration may disrupt the balance of gut microbiota, and intervention strategies need to be evaluated and sought.
   • Formulation innovation To address the issue of poor water solubility, develop new delivery systems (such as nano formulations and prodrugs) to improve efficacy and reduce side effects.

Conclusion

Deoxycholic acid, a natural molecule derived from cholesterol metabolism and gut microbiota, has evolved from a simple digestive cofactor to a multifunctional signaling regulatory hub. It precisely acts on key receptors such as TGR5 and FXR, and is widely involved in core physiological and pathological processes such as choleretic, metabolic, immune, and inflammatory processes. Although its high lipid solubility and complex biological effects pose challenges in drug development, the success of existing clinical applications (such as lipid solubilization) and its enormous potential as a lead compound for the treatment of metabolic diseases fully demonstrate its important pharmaceutical value. Future research needs to focus on in-depth analysis of its specific signaling network in different tissues and concentrations, and optimize its pharmacokinetic properties and targeting through medicinal chemistry and formulation methods, in order to develop safer and more effective new therapeutic drugs based on deoxycholic acid structure, benefiting patients in the fields of metabolic syndrome, liver disease, and inflammatory diseases. The continuous exploration of deoxycholic acid will also deepen our understanding of the complex interaction network of "host metabolite microbiota" in health and disease.