Efficacy of horse oil on lipopolysaccharide-induced inflammation in human keratinocyte.

OBJECTIVE: To investigate the efficacy of horse oil on lipopolysaccharide (LPS)-induced inflammation in human keratinocytes. METHODS: Western blot analysis was performed to measure the expression of cyclooxygenase-2 (COX-2) and IκBα. ELISA was used to analyze prostaglandin E2 (PGE2) levels. RESULTS: Horse oil decreased LPS-induced COX-2 and PGE2 levels in a dose-dependent manner. Nuclear factor-kappa B (NF-κB) plays a key role in the expression of inflammatory cytokines and mediators. Therefore, we investigated the influence of horse oil on the NF-κB signaling pathways. Horse oil inhibited translocation of NF-κB from the cytosol to the nucleus. Furthermore, LPS-induced degradation of IκBα was recovered by horse oil. The activation of p38 mitogen-activated protein kinase (MAPK) reportedly induces degradation of IκBα In agreement with this, LPS activated p38 MAPK and caused IκBα degradation. Conversely, horse oil inhibited LPS-induced p38 MAPK activation and IκBα degradation. In addition, a specific p38 MAPK inhibitor, SB203580, blocked IκBα degradation. CONCLUSION: Horse oil decreased COX-2 and PGE2 by inhibiting p38 MAPK activation, IκBα degradation, and the translocation of NF-κB.

Baicalin-induced Akt activation decreases melanogenesis through downregulation of microphthalmia-associated transcription factor and tyrosinase.

Scutellaria baicalensis has been used topically to treat inflammatory skin diseases in traditional East Asian medicine. Because post-inflammatory hyperpigmentation of the skin is difficult to manage, we investigated the effects of baicalin, a major component of S. baicalensis, on melanin synthesis in Mel-Ab cells. Our data showed that baicalin significantly inhibited melanin production and tyrosinase activity in a dose-dependent fashion, but it did not directly influence tyrosinase activity. Moreover, baicalin treatment triggered decreases in both mRNA and protein levels of microphthalmia-associated transcription factor (MITF) and tyrosinase. Although AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK) activation were induced in baicalin-treated Mel-Ab cells, they were not responsible for baicalin-induced hypopigmentation. Because the Akt pathway is also known to be involved in regulation of melanogenic protein expression and melanin synthesis, we examined the effects of baicalin on the Akt pathway. Our results showed that baicalin treatment stimulated Akt activation. Treatment with LY294002, a specific Akt inhibitor, restored baicalin-induced melanogenesis inhibition and abolished MITF and tyrosinase downregulation by baicalin. Taken together, our data suggest that Akt activation by baicalin inhibits melanin production via downregulation of MITF and tyrosinase in Mel-Ab cells.

Induction of cell growth arrest and apoptotic cell death in human breast cancer MCF-7 cells by the COX-1 inhibitor FR122047.

Non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzyme cyclooxygenase (COX), are known to have a potent anti-tumorigenic activity in various cancers. However, the responsible molecular mechanisms of COX inhibition in breast cancer cells remain to be completely elucidated. We examined the effect of the selective COX-1 inhibitor, FR122047 and the selective COX-2 inhibitor, SC791 on cell growth and apoptosis in human breast cancer MCF-7 cells which exhibited a high basal level of COX-1 expression. Compared to SC791, FR122047 treatment led to a distinct suppression of cell growth in MCF-7 cells. Upon FR122047 treatment, there were apparent increases in the ratio of Bax to Bcl-2, mitochondrial cytochrome c release, and apoptosis in MCF-7 cells. Our data showed that treatment of caspase-8 inhibitor could significantly suppress the cleavage of the effector caspase-7 and PARP in FR122047-treated MCF-7 cells which are caspase-3-deficient breast cancer cells, indicating that the induction of apoptosis by FR122047 is significantly dependent on caspase-8 activity in MCF-7 breast cancer cells. Our data suggest that the NSAID FR122047 may have an anti-cancer potential in breast cancer.