Genipin, a compound derived from Inchin-ko-to, a traditional Chinese/Japanese herbal medicine, markedly suppresses Fas-mediated liver apoptosis and injury in a mouse model of fulminant hepatitis.

According to Japanese researchers writing in the February issue of Gastroenterology, this finding may explain the known efficacy of Inchin-ko-to in the treatment of liver disorders in humans.

Dr. Masahiro Yamamoto,from Tsumura Central Research Laboratories in Ibarki,and colleagues explain that in previous studies they have shown that Inchin-ko-to andits constituents strongly inhibit hepatocyte apoptosis mediated by transforming growth factor-beta.

In the present study, the authors used a mouse model of fulminant hepatitis in order to determine whether or not Inchin-ko-to inhibited Fas-induced liver cell apoptosis.

The investigators found that IV injection of 6.7 mcg of the anti-Fas antibody Jo2 resulted in acute liver failure and death in all treated animals within 24 hours. At a nonlethal dose of 3.3 mcg, Jo2 induced detectable apoptosis within 1 hour.

By comparison, according to the paper, "pretreatment with Inchin-ko-to rescued 75% of Jo2-treated mice and markedly suppressed liver cell apoptosis/injury." Dr. Yamamoto’s team discovered that genipin, a major component of Inchin-ko-to, was an "active principle" that blocked Fas-stimulated apoptosis in mouse hepatocytes.

They also observed that pretreatment with genipin resulted in increased activity of liver cell caspases 3 and 8, and a very rapid reduction in mitochondrial membrane potentials. In addition, livers from mice pretreated with genipin were resistant to calcium-induced mitochondrial permeability transitions.

In light of their observations, Dr. Yamomoto’s team believes "that the antiapoptotic activity of genipin via the interference with mitochondrial permeability transition is a possible mechanism for therapeutic effects of Inchin-ko-to."
　　(From Reuters Health)