Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
Int J Mol Med. 2012 Oct;30(4):974-8. doi: 10.3892/ijmm.2012.1057. Epub 2012 Jul 12.
In the present study, we investigated the effect of guggulsterone on melanogenesis in B16 melanoma cells and elucidated its possible mechanism of action. The effects of guggulsterone on melanogenesis were determined by assaying melanin synthesis and cellular tyrosinase activity in B16/F10 mouse melanoma cells. Guggulsterone dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis and cellular tyrosinase activity with no cytotoxicity. Decreased melanin biosynthesis was accompanied by the reduced expression of melanogenesis-related genes, such as tyrosinase, microphthalmia-associated transcription factor, tyrosinase-related protein (TRP)-1 and TRP-2. Guggulsterone also inhibited α-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. Co-incubation with chenodeoxycholic acid, a well-known farnesoid-X receptor agonist, did not affect IBMX-induced melanogenesis. These results suggest that guggulsterone exerts a melanogenic inhibitory effect through the downregulation of tyrosinase expression.
在本研究中，我们研究了古卡索醇对 B16 黑素瘤细胞黑素生成的影响，并阐明了其可能的作用机制。通过测定 B16/F10 小鼠黑素瘤细胞中黑色素合成和细胞酪氨酸酶活性来确定古卡索醇对黑素生成的影响。古卡索醇可剂量依赖性地抑制异丁基甲基黄嘌呤（IBMX）诱导的黑素生成和细胞酪氨酸酶活性，而无细胞毒性。黑色素生物合成的减少伴随着黑色素生成相关基因（如酪氨酸酶、小眼畸形相关转录因子、酪氨酸酶相关蛋白（TRP）-1 和 TRP-2）表达的降低。古卡索醇还抑制了α-黑素细胞刺激激素或forskolin 诱导的黑素生成增加，表明其对 cAMP 依赖性黑素生成途径有作用。与鹅脱氧胆酸共孵育，一种众所周知的法尼醇 X 受体激动剂，不影响 IBMX 诱导的黑素生成。这些结果表明，古卡索醇通过下调酪氨酸酶表达发挥黑素生成抑制作用。
