Zhang Jie, Zhu Wan-Fang, Zhu Wei-Yuan, Yang Pan Pan, Xu Jian, Manosroi Jiradej, Kikuchi Takashi, Abe Masahiko, Akihisa Toshihiro, Feng Feng
Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P. R. China.
Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Chem Biodivers. 2018 Feb;15(2). doi: 10.1002/cbdv.201700486. Epub 2018 Feb 5.
A new steroid, 20-hydroxyisofucosterol (stigmasta-5,24(28)-diene-3β,20β-diol) (7), along with six known compounds 1 - 6 were isolated from the MeOH extract of the leaves of Sauropus androgynus L. Merr. (Euphorbiaceae). The structure of new steroid was determined by HR-APCI-MS and various NMR techniques in combination with literature data. Subsequently, their anti-inflammatory, cytotoxic activities against five human cell lines, as well as inhibitory activities against the α-MSH induced melanogenesis on the B16 cell line were evaluated. As the results, steroid compounds, 6 and 7 exhibited moderate cytotoxic to HL60, AZ521, SKBR3, and A549 tumor cell lines (IC 26.9 - 45.1 μm) with high tumor selectivity for A549 relative to WI38 cell lines (SI 2.6 and 3.0, resp.). And, flavonoid compounds, 4 and 5 exhibited superior inhibitory activities against melanogenesis (67.0 - 94.7% melanin content), even with no or low toxicity to the cells (90.1 - 99.6% cell viability) at the concentrations from 10 to 100 μm. Furthermore, Western blot analysis suggested that compound 5 could inhibit melanogenesis by suppressing the protein expressions of MITF, TRP-1, TRP-2, and tyrosinase.
从白饭树（大戟科）叶片的甲醇提取物中分离出一种新的甾体化合物20-羟基异岩藻甾醇（豆甾-5,24(28)-二烯-3β,20β-二醇）（7）以及六种已知化合物1 - 6。通过高分辨大气压化学电离质谱（HR-APCI-MS）和各种核磁共振技术并结合文献数据确定了新甾体化合物的结构。随后，评估了它们的抗炎活性、对五种人类细胞系的细胞毒性活性以及对α-促黑素（α-MSH）诱导的B16细胞系黑色素生成的抑制活性。结果显示，甾体化合物6和7对HL60、AZ521、SKBR3和A549肿瘤细胞系表现出中等细胞毒性（IC₅₀为26.9 - 45.1 μM），相对于WI38细胞系，对A549具有较高的肿瘤选择性（选择性指数分别为2.6和3.0）。并且，黄酮类化合物4和5对黑色素生成表现出优异的抑制活性（黑色素含量为67.0 - 94.7%），在10至100 μM浓度下对细胞无毒性或毒性较低（细胞活力为90.1 - 99.6%）。此外，蛋白质印迹分析表明化合物5可通过抑制小眼畸形相关转录因子（MITF）、酪氨酸酶相关蛋白-1（TRP-1）和酪氨酸酶相关蛋白-2（TRP-2）以及酪氨酸酶的蛋白表达来抑制黑色素生成。
