Ursodeoxycholic acid

Bile acids (BAs) are natural detergents that solubilize dietary lipids in the intestinal tract. They are also important signaling molecules. BA regulate not only their own synthesis, but also have a role in metabolic syndrome, obesity, and diabetes. High concentrations of hydrophobic BA such as deoxycholic acid produce deleterious effects in liver disorders. Among the different mechanisms triggered by them, there is evidence that they induce cell death via apoptosis. Sodium deoxycholate (NaDOC) activates cell death receptor independently of ligands, stimulates p53, EF2-1 and Cyclin D1 expression, and induces oxidative damage, mitochondrial swelling and glutathione (GSH) depletion. Any of these alterations are enough to activate caspases leading to cell death by apoptosis. More hydrophilic BAs such as ursodeoxycholic acid (UDCA) prevents the reactive oxygen species formation, mitochondrial dysfunction and death receptor induced apoptosis, blocking the apoptosis. The anti-apoptotic effects of UDCA were initially observed in hepatocytes, not only due to an inhibition of ROS production but also by avoiding the release of pro-apoptotic factors from the mitochondria. Due to the protective properties against cytotoxic BAs, UDCA has been used as a first choice treatment for a number of cholestatic liver diseases, mainly primary biliary cirrhosis.

As we know, liver cancer is the second most common cause of cancer death worldwide. Several studies illustrate that constitutive nuclear factor-κB (NF-κB) activity plays a central role in the hepatic neoplastic progression through the upregulation of anti-apoptotic genes. Moreover, the inhibition of NF-κB activation in hepatocytes retards and reduces the development of hepatocellular carcinoma in mice. Therefore, the inhibition of NF-κB activation might be an effective strategy to treat liver cancers.

Glycyrrhizin, the triterpenoid saponin from Glycyrrhiza glabra L. roots (licorice), consists of one molecule of glycyrrhetinic acid and two molecules of glucuronic acid. Glycyrrhizin exhibits various pharmacological effects, such as anti-inflammatory and protective effects in liver. Therefore, glycyrrhizin analogs, such as magnesium isoglycyrrhizinate and stronger neo-minophagen C, are effective and safe for the treatment of patients with chronic liver disease and liver dysfunction.

Silymarin is a flavonolignan complex from Silybum marianum (L.) Gaertn. fruits. Silymarin comprises a number of flavonolignans, including silibinin (silybin A and silybin B), isosilybin A and B, silychristin A and B, silydianin, and other phenolic compounds. Silymarin exhibits anti-inflammatory and immunomodulatory effects and thus promotes the health of livers. In addition, silymarin-type drugs like legalon have been used for the treatment of acute hepatitis and nonalcoholic fatty liver disease in patients.

Silymarin – CAS 65666-07-1

Ursodeoxycholic acid, a hydrophilic stereoisomer of chenodeoxycholic acid, is a major component of Chinese black bear’s bile. Ursodeoxycholic acid is used to treat chronic cholestatic liver diseases, such as primary biliary cirrhosis and primary sclerosing cholangitis. Moreover, some evidences indicate that ursodeoxycholic acid decreases the levels of alanine aminotransferase, aspartate aminotransferase, and gammaglutamyl transpeptidase in patients with chronic hepatitis C and protects livers from against methotrexate-induced toxicity.

Ursodeoxycholic acid CAS 128-13-2

In addition to this, ursodeoxycholic acid is a tertiary bile acid in humans, and large doses have been used as a hepatoprotective drug in the treatment of antivirus therapy non-responsive chronic hepatitis C and primary biliary cirrhosis. Although the detailed mechanism of its hepatoprotective effect remains to be clarified, it may be due to its antioxidative effect and protection against apoptosis caused by mitochondria injury.

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