Licorice and enzymes other than 11 beta-hydroxysteroid dehydrogenase: an evolutionary perspective

Licorice has long been known to promote the healing of ulcers. In the 1950s, studies with licorice-derived compounds revealed that the anti-ulcer effects of licorice are due to inhibition of 15-hydroxyprostaglandin dehydrogenase and delta 13-prostaglandin reductase. 15-Hydroxyprostaglandin dehydrogenase converts prostaglandins E2 and F2 alpha to 15-ketoprostaglandins, which are inactive. delta 13-Prostaglandin reductase metabolizes the inactive delta 13-prostaglandin to 13,14-dihydro,15-ketoprostaglandin, which is further metabolized and excreted in urine. Thus, licorice-derived compounds have the effect of raising the local concentration of prostaglandins that promote mucous secretion and cell proliferation in the stomach, leading to healing of ulcers. 11 beta-Hydroxysteroid dehydrogenase, which also is inhibited by licorice-derived compounds, shares a common ancestor with 15-hydroxyprostaglandin dehydrogenase. Both enzymes are homologous to Streptomyces hydrogenans 3 alpha,20 beta-hydroxysteroid dehydrogenase, which also is inhibited by licorice. Thus, licorice inhibits enzymes that diverged at least 2 billion years ago from a common ancestor. Other oxidoreductases in bacteria, plants, and animals that are inhibited by licorice-derived compounds are likely to be discovered in the future.