Okinawa Industrial Technology Center, Suzaki 12-2, Uruma City, Okinawa 904-2234, Japan.
Department of Biometabolic Chemistry, School of Health Science, Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara-Cho, Okinawa 903-0215, Japan.
Fitoterapia. 2018 Sep;129:94-101. doi: 10.1016/j.fitote.2018.06.015. Epub 2018 Jun 19.
Inhibition of poly(ADP-ribose) polymerase 1 (PARP1) is one of the most promising strategies for cancer chemotherapy, and a number of inhibitors possessing nicotinamide-like structures are being developed. To discover new types of PARP1 inhibitors, we screened a large number of substances of plant origin and isolated two inhibitory substances from the leaves of Syzygium samarangense (Blume) Merrill & L.M. Perry. The inhibitory substances were identified as vescalagin and its epimer castalagin by analyses using nuclear magnetic resonance and mass spectrometry. The IC of purified vescalagin and castalagin for PARP1 inhibition were 2.67 and 0.86 μM, respectively. Unlike most of synthetic PARP1 inhibitors, castalagin showed a mixed type inhibition, of which Ki was 1.64 μM. When SH-SY5Y cells were treated with these ellagitannins at concentrations of less than 5 μM, cellular poly(ADP-ribosyl)ation was obviously attenuated. Castalagin and vescalagin also possessed inhibitory activity against DNA topoisomerase II, implying that they function as dual inhibitors in cells.
聚 ADP-核糖聚合酶 1（PARP1）的抑制是癌症化疗最有前途的策略之一，许多具有烟酰胺样结构的抑制剂正在被开发中。为了发现新型 PARP1 抑制剂，我们筛选了大量植物来源的物质，并从 Syzygium samarangense（Blume） Merrill & L.M. Perry 的叶子中分离出两种具有抑制作用的物质。通过使用核磁共振和质谱分析，鉴定出这两种抑制物质分别为鞣花酸和其差向异构体诃黎酸。纯化的鞣花酸和诃黎酸对 PARP1 的抑制 IC 分别为 2.67 和 0.86 μM。与大多数合成的 PARP1 抑制剂不同，诃黎酸表现出混合抑制类型，其 Ki 为 1.64 μM。当 SH-SY5Y 细胞用低于 5 μM 的这些鞣花单宁处理时，细胞的多聚 ADP-核糖化明显减弱。诃黎酸和鞣花酸也对 DNA 拓扑异构酶 II 具有抑制活性，表明它们在细胞中作为双重抑制剂发挥作用。
