Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine.
Goldenseal is an herb which is widely used for many medical applications such as in eyewashes and skin lotions and which is currently undergoing testing by the National Toxicology Program. The main alkaloid constituent of Goldenseal is berberine. The topical application of Goldenseal or berberine to the skin or eyes raises the possibility that an adverse phototoxic reaction may result from an interaction between the alkaloid and light. We have therefore studied the photochemistry of berberine in different solvents and its phototoxicty to HaCaT keratinocytes. Irradiation of berberine in aqueous solutions does not generate (1)O(2), but in CH(2)Cl(2), (1)O(2) is produced with a quantum yield phi = 0.34. With the aid of the electron paramagnetic resonance (EPR) spin trapping technique and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we have detected oxygen-centered radicals photogenerated by berberine in water and acetonitrile. In the latter solvent and in the absence of oxygen, the neutral berberine radical formed by one electron reduction was observed. Methanol radicals were detected by EPR in water/alcohol low-temperature glasses irradiated in the berberine long-wavelength absorption band. In such alcoholic glasses, we have also detected an EPR signal from the berberine triplet at 77 K, in contrast to aqueous glasses where neither triplet nor radicals were detectable. Our data show that, although a weak photosensitizer in water, berberine is able to produce both (1)O(2) and radical species in a nonpolar environment. UVA irradiation of HaCaT keratinocytes in the presence of 50 microM 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 emitting UVA should be avoided when topical preparations derived from Goldenseal or containing berberine are used.
Inbaraj
J J
JJ
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Kukielczak
B M
BM
Bilski
P
P
Sandvik
S L
SL
Chignell
C F
CF
D000287:Administration, Topical; D001599:Berberine / Q000737:chemistry* / Q000633:toxicity*; D018929:Cell Culture Techniques; D002470:Cell Survival; D004249:DNA Damage; D017484:Dermatitis, Phototoxic / Q000503:physiopathology*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D010084:Oxidation-Reduction; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity; D029626:Ranunculaceae / Q000737:chemistry*; D012997:Solvents; D014466:Ultraviolet Rays
D005609:Free Radicals; D017319:Photosensitizing Agents; D010936:Plant Extracts; D012997:Solvents; D001599:Berberine