College of Korean Medicine, Gachon University, Seongnam 13120, South Korea.
School of Pharmacy, Sungkyunkwan University, Suwon 16419, South Korea.
J Ethnopharmacol. 2018 Mar 1;213:48-55. doi: 10.1016/j.jep.2017.10.025. Epub 2017 Nov 2.
Curcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds.
This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea.
Repeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the C. zedoaria MeOH extract. The cytotoxic effects of the C. zedoaria MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis.
The MeOH extract of C. zedoaria rhizomes exerted a cytotoxic effect on AGS cells (IC: 96.60 ± 4.87μg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (1), germacrone (2), curzerenone (3), curcumenol (4), and curcuzedoalide (5). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC value of 125.11±2.77μM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells.
These data indicate that curcuzedoalide contributed to the cytotoxicity of C. zedoaria by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.
姜黄（姜科），又名白姜黄或莪术，在印度阿育吠陀和中药中被用于治疗各种癌症，其含有多种倍半萜类化合物。
本研究旨在评估莪术根茎的甲醇（MeOH）提取物及其活性成分对韩国常见癌症胃癌的治疗作用。
采用反复柱层析和半制备高效液相色谱法从莪术 MeOH 提取物中分离生物活性成分。采用人胃癌 AGS 细胞测定莪术 MeOH 提取物及其活性化合物的细胞毒性。采用 Western blot 分析评估与细胞凋亡相关的蛋白表达。
莪术根茎的 MeOH 提取物对 AGS 细胞具有细胞毒性（IC：96.60±4.87μg/mL）。基于对增殖活性的生物活性导向分离，对 MeOH 提取物的化学研究导致分离出包括异莪术醇（1）、大根香叶烯酮（2）、莪术酮（3）、莪术醇（4）和莪术环二肽（5）在内的 5 种倍半萜。其中，莪术环二肽以剂量依赖方式抑制胃癌细胞增殖的作用最强，IC 值为 125.11±2.77μM。Western blot 分析表明，莪术环二肽通过激活 caspase-8、caspase-9、caspase-3 和 PARP 抑制 AGS 人胃癌细胞活力，导致 AGS 人胃癌细胞凋亡性死亡。
这些数据表明，莪术环二肽通过激活 caspase 和 PARP 的切割，对莪术的细胞毒性有贡献，caspase 和 PARP 是凋亡的代表性标志物。因此，莪术环二肽是开发新型化疗药物的一个有希望的候选物。
