Biol. Pharm. Bull. 30(5) 928—934 (2007)

damage. UVB exposure of human skin induces skin alterations, including erythema, which is characteristic of sunburn cells, and prolonged UVB exposure results in the formation of wrinkles, the degradation of matrix molecules, the development of elastosis, and an increased risk of epithelial skin cancer. Keratinocytes are the main target of UV, and play a central role in several responses of photodamage after UV exposure by means of the release of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-a . IL-1 is a potent inducer of IL-6, and one may speculate that the release of IL-6 by keratinocytes after UV exposure is mediated by the release of IL-1 in an autocrine or paracrine manner. Induction of IL-10 and TNF-a by UV results in systemic immunosuppression, and IL-6 and IL-8 induce the acute-phase response and stimulates leukocyte infiltration in the skin. These pro-inflammatory cytokines are considered to be closely related to the progression of photodamage. An additional process of photodamage is apoptosis in cells that contain a high proportion of damaged DNA following UV irradiation. The primary mediator responsible for removing UVB-induced DNA damage of keratinocytes in skin is believed to be p53, which activates downstream genes and subsequently induces cell-cycle arrest in the G1-S phase to repair DNA mutations. If the cells have excessive unrepaired DNA damage, a process that leads to fragmentation of the DNA is initiated and apoptotic sunburn cells are formed. In this way, apoptosis is considered to act as a crucial mechanism for the elimination of keratinocytes damaged by UV irradiation. In recent years it has been indicated that the molecular mechanisms of inflammation and apoptosis are similar, and this finding suggests that inflammation and apoptosis are related to the repair and recover of UVB-induced cell and tissue damage. To search for an effective compound to protect skin against these deleterious effects of UV, we examined the effects of various substances on human keratinocytes using inflammatory cytokine production and cell viability as indexes of photodamage. We examined various substances and found that the root extract of Lithospermum erythrorhizon (SK) suppresses UVB damage. SK contains naphthoquinone derivatives, which have been reported to have anti-inflammatory, anti-bacterial, and anti-tumor effects, and scavenging activity against several types of reactive oxygen species (ROS). However, the cellular and molecular mechanisms by which SK inhibits UVB-induced damage are not clear. In this study, we demonstrated that SK protects human keratinocytes from UVB-induced damage in vitro.