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Increased matrix metalloproteinase 1 (MMP‐1) expression is a feature of photo‐aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation–induced MMP‐1 expression and apoptosis using human dermal fibroblasts. UVB irradiation not only increased MMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells from UVB irradiation–induced apoptosis, but only baicalein inhibited MMP‐1 expression. UVB irradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activated TRPV1 channels. The resulting UVB irradiation–induced Ca2+ increase was blocked by the 12‐lipoxygenase inhibitor baicalein and the TRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane. UVB irradiation also increased ROS generation and decreased Nrf2 protein levels. UVB irradiation–induced MMP‐1 expression was blocked by the Ca2+ chelator BAPTA, by capsazepine and by TRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine. ERK phosphorylation and JNK phosphorylation were induced by UVB irradiation, but only ERK phosphorylation was Ca2+ sensitive. Increased MMP‐1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP‐1 expression is mediated by increased cytosolic Ca2+ and ERK phosphorylation. UVB irradiation–induced ROS generation is also Ca2+ sensitive, and UVB irradiation–induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation–induced cytosolic Ca2+ increase, protects cells from UVB irradiation–induced MMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellular ROS, protects cells from only UVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin. [ABSTRACT FROM AUTHOR]

In this study, we characterized the effect of baicalein on the regulation of keratinocyte differentiation and proliferation, which are abnormal in atopic dermatitis or psoriasis. Treatment of HaCaT keratinocytes with 10 μ m baicalein slightly inhibited cell growth, caused morphological differentiation and increased expression of keratins 1 and 10 (K1/K10) without affecting ROS generation, cytochrome c release or apoptosis. Baicalein treatment caused growth arrest in G0/G1 phase and also induced Ca2+ influx via TRPV4 receptor activation. Phosphorylation of ERK, Akt and p38 MAPK, but not JNK, was increased by baicalein, and inhibition of phosphorylation of ERK, but not that of Akt or p38 MAPK, blocked the baicalein-induced increase in K1/K10 expression, suggesting that ERK activation is involved in this increase. Removal of extracellular Ca2+ or blockade of Ca2+ influx by pharmacological inhibition or silencing of the TRPV4 receptor did not affect growth arrest, ROS generation or apoptosis, but inhibited baicalein-induced ERK phosphorylation and K1/K10 expression. Thus, baicalein treatment increases differentiation, and decreases proliferation, of keratinocytes. The mechanism of differentiation of keratinocytes is distinct from that of proliferation, the former being Ca2+ dependent and the latter Ca2+ independent. [ABSTRACT FROM AUTHOR]