Lupenone from Erica multiflora Leaf Extract Stimulates Melanogenesis in B16 Murine Melanoma Cells through the Inhibition of ERK1/2 Activation
Lupenone from Erica multiflora Leaf Extract Stimulates Melanogenesis in B16 Murine Melanoma Cells through the Inhibition of ERK1/2 Activation
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DOI：
10.1055/s-0032-1328189
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发表时间：
2013-03-01
期刊：
影响因子：
2.7
通讯作者：
Isoda, Hiroko
中科院分区：
文献类型：
--
作者：
Villareal, Myra O.;Han, Junkyu;Isoda, Hiroko
色素减退疾病通常使用UVB光进行治疗，这会增加患者患皮肤癌的风险。在这里，我们评估了黑素生成刺激作用的叶提取物的埃里卡多花，药用植物从地中海地区，其活性成分，lup-20（29）-en-3-one，作为可能的治疗剂，以解决色素减退症。用E.多花提取物或其活性成分羽扇豆酮，以评价它们对黑色素生物合成的影响。还确定了所观察到的影响的机制。15个乙酸乙酯级分的生物活性指导分级鉴定了级分2具有黑素生成刺激作用，这是由于其能够降低促分裂原活化蛋白激酶磷酸化细胞外信号调节激酶1和2的活化。乙酸乙酯级分2的薄层层析显示存在作为主要生物活性组分的up-20（29）-烯-3-酮。用lup-20（29）-en-3-one处理的B16细胞增加黑色素含量，而无细胞毒性。为了确定所观察到的lup-20（29）-烯-3-酮的作用的机制，测定酪氨酸酶活性、酪氨酸酶蛋白表达和磷酸化细胞外信号调节激酶1和2的活化。此外，使用实时PCR定量酪氨酸酶mRNA的表达。结果表明，lup-20（29）-en-3-one对酪氨酸酶活性没有影响，但能在转录和翻译水平上增加酪氨酸酶的表达。酪氨酸酶mRNA表达的增加最有可能是由于抑制促分裂原活化蛋白激酶磷酸化细胞外信号调节激酶1和2的活化。本文首次报道了E.多花乙酸乙酯提取物及其活性化合物LUP-20（29）-烯-3-酮通过促分裂原活化的蛋白激酶磷酸化的细胞外信号调节激酶1和2的磷酸化抑制而增加酪氨酸酶的表达，从而刺激黑素生成，使其成为色素减退疾病的可能治疗方法。
Hypopigmentation diseases are usually managed using UVB light which increases the patients' risk for skin cancer. Here, we evaluated the melanogenesis stimulatory effects of leaf extracts of Erica multiflora, a medicinal plant from the Mediterranean region, and its active component, lup-20 (29)-en-3-one, as possible therapeutic agents to address hypopigmentation disorders. B16 murine melanoma cells were treated with E. multiflora extracts or its active component lupenone to evaluate their effects on melanin biosynthesis. The mechanism underlying the observed effects was also determined. Bioactivity-guided fractionation of fifteen ethyl acetate fractions identified fraction 2 to have melanogenesis stimulatory effects due to its ability to decrease mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. Preparative TLC of ethyl acetate fraction 2 revealed the presence of lup-20(29)-en-3-one as the major bioactive component. B16 cells treated with lup-20(29)-en-3-one increased melanin content without cytotoxicity. To determine the mechanism for the observed effects of lup-20(29)-en-3-one, the tyrosinase enzyme activity, the tyrosinase protein expression, and the activation of phosphorylated extracellular signal-regulated kinases 1 and 2 were determined. In addition, the expression of the tyrosinase mRNA was quantified using real-time PCR. Results showed that lup-20(29)-en-3-one has no effect on the tyrosinase enzyme activity but can increase tyrosinase expression at both the transcriptional and translational levels. The increase in the tyrosinase mRNA expression was most likely due to the inhibited mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 activation. We report for the first time that E. multiflora ethyl acetate extract and its active compound lup-20(29)-en-3-one stimulate melanogenesis by increasing the tyrosinase enzyme expression via mitogen-activated protein kinase phosphorylated extracellular signal-regulated kinases 1 and 2 phosphorylation inhibition, making it a possible treatment for hypopigmentation diseases.