New TNF-alpha releasing inhibitors, geraniin and corilagin, in leaves of Acer nikoense, Megusurino-ki

The success of green tea as a cancer preventive is based on evidence that g reen tea contains tannins and antioxidants, does not show toxicity in human s and has long traditional use in Asia. In the light of this, herbal medici nes are now also attracting attention as potential sources of cancer preven tive agents. Using the inhibition of TNF-a release assay, we studied Acer n ikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhib itory activity of TNF-a release was found in the leaf extract rather than t he bark extract, and the main active constituents were identified as gerani in and corilagin, which are present in another Japanese traditional herb, G eranium thunbergii (Genno-shoko). The IC50 values of TNF-alpha release inhi bition were 43 muM for geraniin and 76 muM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 muM. Treatment with geraniin pri or to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-beari ng mice from 80.0 to 40.0% and the average numbers of tumor per mouse from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activi ty than EGCG. Since geraniin and corilagin have been well investigated as r epresentative tannins, we discuss here the new possibility of classical her bal medicine in the development of preventive agents for cancer and other l ife-style related diseases.