The flavonolignan silibinin from Silybum marianum targets hepatic lipid biosynthesis and elevates the hepatic biotransformation capacity

Silibinin is considered as major active component of Silybum marianum (milk thistle) extracts and is traditionally used for the treatment of toxic liver damage and as unique therapy for intoxication with Amanita phalloides. However, the molecular mechanisms of silbinin remained enigmatic. Membrane-stabilizing properties of silibinin, modulation of the function of membrane proteins as well as effects on metabolism have been discussed since decades. Here, we show that silibinin and even more pronounced the milk thistle-containing phytopharmaceutical Silimarit® significantly increase the content of major phospholipid classes in human monocytes and hepatocellular carcinoma cells in vitro as well as in murine liver in vivo. The accumulation of phospholipids arises from intracellular membranes and could partially be ascribed to changes in the expression and activation of enzymes in fatty acid metabolism. The enrichment of hepatic phospholipids and expansion of intracellular membranes is associated with an increased expression of ER-localized metabolizing enzymes and elevated biotransformation capacity of mouse liver. Taken together, we provide a link between hepatic fatty acid/phospholipid biosynthesis and biotransformation, which might contribute to the liver-protective properties of silibinin related to intoxication as well as metabolic diseases such as steatosis and cirrhosis.

Publication History

Article published online:
13 December 2021