Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV 1‐Ca‐ ERK pathway in ultraviolet B–irradiated human dermal fibroblasts

Abstract 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–inducedMMP‐1 expression and apoptosis using human dermal fibroblasts.UVBirradiation not only increasedMMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells fromUVBirradiation–induced apoptosis, but only baicalein inhibitedMMP‐1 expression.UVBirradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activatedTRPV1 channels. The resultingUVBirradiation–induced Ca2+increase was blocked by the 12‐lipoxygenase inhibitor baicalein and theTRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane.UVBirradiation also increasedROSgeneration and decreased Nrf2 protein levels.UVBirradiation–inducedMMP‐1 expression was blocked by the Ca2+chelatorBAPTA, by capsazepine and byTRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine.ERKphosphorylation andJNKphosphorylation were induced byUVBirradiation, but onlyERKphosphorylation was Ca2+sensitive. IncreasedMMP‐1 expression was blocked byPD98059, but not bySP600125. Thus, increasedMMP‐1 expression is mediated by increased cytosolic Ca2+andERKphosphorylation.UVBirradiation–inducedROSgeneration is also Ca2+sensitive, andUVBirradiation–induced apoptosis is caused by increasedROS. Thus, baicalein, by blocking theUVBirradiation–induced cytosolic Ca2+increase, protects cells fromUVBirradiation–inducedMMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellularROS, protects cells from onlyUVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin.