Ultraviolet light (UV) induces an inflammatory response in the skin by cyclooxygenase (COX)-2 expression and prostaglandin (PG) E2 production. Citrus peel has been used as a natural medicine. It contains polymethoxyflavonoids (PMFs) as a major ingredient, which have anti-inflammatory activity. We obtained orange peel extract containing high levels of PMFs. The extract suppressed UVB-induced COX-2 expression and PGE2 production in HaCaT cells. Furthermore, it was found that this extract acted as a peroxisome proliferator-activated receptor (PPAR)-γ agonist. The suppression of UVB-induced COX-2 expression by this extract was inhibited by GW 9662 and T0070907, which are both PPAR-γ antagonists. It is therefore suggested that orange peel extract, containing high levels of PMFs, suppresses UVB-induced COX-2 expression and PGE2 production through PPAR-γ. Hence, these extracts could provide useful protection against or alleviation of UV damage.

These results suggest that the PMF mixture suppresses the localization of tyrosinase to melanosomes and consequently inhibits melanogenesis due to the acidification of cell organelles, including melanosomes.

Ultraviolet (UV) B is the main cause of skin photoageing, which has characteristic features such as deep wrinkles. UVB increases the expression of matrix metalloproteinases (MMPs) in the skin and can cause wrinkles by disrupting components of the extracellular matrix, such as collagen fibres. We now report that a polymethoxyflavone (PMF) mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1 that involves the inhibition of c-jun N-terminal kinase (JNK) activity. Furthermore, the PMF mixture also inhibits the UVB-induced phosphorylation of JNK. Therefore, the results suggest that the PMF mixture suppresses the UVB- | INTRODUCTIONSkin ageing is divided into intrinsic ageing and photoageing caused by repeated exposure to ultraviolet (UV) radiation. Whereas intrinsic ageing is characterized by smooth, pale and finely wrinkled skin, photoageing has the features of coarse, deep wrinkles, dyspigmentation and telangiectasia.1 Alterations of collagen fibres in the dermis are thought to cause the wrinkles observed in intrinsic ageing and in photoageing due to an imbalance between collagen synthesis and degradation. Collagen is degraded by matrix metalloproteinases (MMPs). Because UV induces the expression of MMPs in the skin, 2 it is considered that the UV-induced expression of MMPs is related to the deep wrinkles seen in photoaged skin.UV radiation has been reported to induce the expression of MMP-1, MMP-3 and MMP-9 in the skin. 3 Following UV irradiation, it is thought that MMP-1 initially disrupts type I and III collagens after which MMP3 and/or MMP-9 further degrade the disrupted collagens. 3The UV-induced expression of MMPs has been observed in the epidermis and dermis, and large amounts of MMPs are produced by the epidermis. 4 The cells producing MMPs in the epidermis are mainly keratinocytes. 2,5Many agents that can suppress the UV-induced expression ofMMPs have been identified. Various flavonoids have been reported to suppress the expression of MMPs. For example, myricetin suppresses MMP-9 and MMP-13 expression induced by UVB, 6,7 and luteolin inhibits UVB-induced MMP-1 expression. 8 We focused on polymethoxyflavone (PMF), which is a flavone where the hydroxyl group is replaced with a methoxy group. PMF has been reported to have anti-inflammatory, 9 anti-atherogenic 10 and antitumor invasion 11,12 effects. Although it has also been reported that PMF suppresses 12-O-tetradecanoylphorbol 13-acetate (TPA) induced MMP expression, 11,12 to our knowledge, it has not been shown whether PMF prevents UVB from inducing MMP-1 expression.In our previous study, a PMF mixture extracted from orange peels was shown to suppress UVB-induced COX-2 expression and PGE 2 production. 13 In this study, we determined whether the PMF mixture inhibits the expression of MMP-1 by UVB-irradiated immortalizedHaCaT human keratinocytes. | METHODS | ReagentsThe PMF mixture was extracted from orange peels and contained PMF at more than 80% and consisted of tangeretin, nobiletin and