| Abstract
| - Juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone) are yellow pigments found in black walnut (Juglans regia). Herbal preparationsderived from black walnut have been used as hair dyes and skin colorants in addition to beingapplied topically for the treatment of acne, inflammatory diseases, ringworm, and fungal,bacterial, or viral infections. We have studied the cytotoxicity of these quinones to HaCaTkeratinocytes. Exposure to juglone or plumbagin (1−20 μM) resulted in a concentration-dependent decrease in cell viability. The cytotoxicity of these quinones is due to two differentmechanisms, namely, redox cycling and reaction with glutathione (GSH). Redox cycling resultsin the generation of the corresponding semiquinone radicals, which were detected by electronparamagnetic resonance. Incubation of keratinocytes with the quinones generated hydrogenperoxide (H2O2) and resulted in the oxidation of GSH to GSSG. Depletion of GSH by buthioninesulfoximine enhanced semiquinone radical production, increased H2O2 generation, and producedgreater cytotoxicity, suggesting that GSH plays an important protective role. Both quinonesdecreased the intracellular levels of GSH. However, plumbagin stoichiometrically convertedGSH to GSSG, indicating that redox cycling is its main metabolic pathway. In contrast, muchof the GSH lost during juglone exposure, especially at the higher concentrations (10 and 20μM), did not appear as GSSG, suggesting that the cytotoxicity of this quinone may also involvenucleophilic addition to GSH. Our findings indicate that topical preparations containing jugloneand plumbagin should be used with care as their use may damage the skin. However, it isprobable that the antifungal, antiviral, and antibacterial properties of these quinones are theresult of redox cycling.
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