Dioscorea bulbiferaL.-induced hepatotoxicity and involvement of metabolic activation of furanoterpenoids

The rhizome ofDioscorea bulbiferaL. (DBL) is a popular traditional herb in the treatment of goiters, breast lumps, and tumors. Unfortunately, DBL can give rise to severe hepatotoxicity. More than 100 cases of liver injury, due to the usage of DBL in China, have been reported in the past half-century. The main toxic components of DBL are furanoditerpenoids diosbulbin B (DSB) as well as 8-epidiosbulbin E (EEA). This toxic effect requires metabolic oxidation of the furan ring mediated by cytochrome P450 enzymes, and the P450 3A subfamily is the main enzyme responsible for the reported hepatotoxicity.cis-Enedial intermediates resulting from furan ring oxidation can react with nucleophilic sites of macromolecules, such as protein and DNA, which may trigger the toxicities. This review illustrates the liver injury induced by DBL including metabolic activation of DSB and EEA, the essential components responsible for DBL-induced hepatotoxicity, along with biochemical mechanisms of their toxic actions. It will facilitate the development of approaches to prevent and intervene in liver injury induced by DBL for its safe use in clinical practice.