New TNF-α 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 green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-α release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-α release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC₅₀ values of TNF-α release inhibition were 43 μM for geraniin and 76 μM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 μM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing 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 activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.