Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine

Goldenseal is an herb which is widely used for many medical applications su ch as in eyewashes and skin lotions and which is currently undergoing testi ng by the National Toxicology Program. The main alkaloid constituent of Gol denseal is berberine. The topical application of Goldenseal or berberine to the skin or eyes raises the possibility that an adverse phototoxic reactio n may result from an interaction between the alkaloid and light. We have th erefore studied the photochemistry of berberine in different solvents and i ts phototoxicty to HaCaT keratinocytes. Irradiation of berberine in aqueous solutions does not generate O-1(2), but in CH2Cl2, O-1(2) is produced with a quantum yield phi = 0.34. With the aid of the electron paramagnetic reso nance (EPR) spin trapping technique and 5,5-dimethyl-1-pyrroline N-oxide (D MPO), we have detected oxygen-centered radicals photogenerated by berberine in water and acetonitrile. In the latter solvent and in the absence of oxy gen, the neutral berberine radical formed by one electron reduction was obs erved. Methanol radicals were detected by EPR in water/alcohol low-temperat ure glasses irradiated in the berberine long-wavelength absorption band. In such alcoholic glasses, we have also detected an EPR signal from the berbe rine triplet at 77 K, in contrast to aqueous glasses where neither triplet nor radicals were detectable. Our data show that, although a weak photosens itizer in water, berberine is able to produce both O-1(2) and radical speci es in a nonpolar environment. UVA irradiation of HaCaT keratinocytes in the presence of 50 muM berberine resulted in an 80% decrease in cell viability and a 3-fold increase in DNA damage as measured by the Comet assay. These findings suggest that exposure to sunlight or artificial light sources emit ting UVA should be avoided when topical preparations derived from Goldensea l or containing berberine are used.