Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
J Nat Med. 2021 Sep;75(4):915-925. doi: 10.1007/s11418-021-01541-x. Epub 2021 Jun 29.
Two phenylpropanoid-conjugated iridoids, deglucosyl gaertneroside (1) and morindoidin (2), were isolated from the leaves of Morinda morindoides (Rubiaceae) by activity-guided fractionation using an anti-malarial activity assay. The known related iridoids molucidin (3) and prismatomerin (4), two lignans, abscisic acid, two megastigmanes, and two flavonol glycosides were also identified. The structures of isolated compounds were elucidated using spectroscopic analysis. The isolated compounds were evaluated for anti-malarial activity against the chloroquine/mefloquine-sensitive strains of Plasmodium falciparum together with cytotoxicity against adult mouse brain cells. Potent anti-malarial activity of 3 and 4 (IC of 0.96 and 0.80 μM, CC of 1.02 and 0.88 μM, and SI of 1.06 and 1.10, respectively) was shown, while new iridoids 1 and 2 and pinoresinol (5) displayed moderate activity (IC of 40.9, 20.6, and 24.2 μM) without cytotoxicity (CC > 50 μM). These results indicate that 1-5 may be promising lead compounds for anti-malarial drugs. In addition, our results imply the necessity of the quality control of the extract of M. morindoides leaves based on the contents of 1-5 in terms of the safety and efficacy.
两种苯丙素共轭环烯醚萜苷，去葡萄糖基加特纳苷（1）和莫林苷（2），通过抗疟活性测定的活性导向分离从巴戟天（茜草科）叶中分离得到。还鉴定了已知的相关环烯醚萜苷木栓酮（3）和棱柱醇（4）、两种木脂素、脱落酸、两种megastigmanes 和两种黄酮醇糖苷。通过光谱分析阐明了分离化合物的结构。评估了分离得到的化合物对氯喹/甲氟喹敏感株疟原虫的抗疟活性以及对成年小鼠脑细胞的细胞毒性。3 和 4 表现出很强的抗疟活性（IC 为 0.96 和 0.80 μM，CC 为 1.02 和 0.88 μM，SI 为 1.06 和 1.10），而新的环烯醚萜 1 和 2 以及松脂素（5）显示出中度活性（IC 为 40.9、20.6 和 24.2 μM）而无细胞毒性（CC>50 μM）。这些结果表明，1-5 可能是有希望的抗疟药物先导化合物。此外，我们的结果表明，基于 1-5 的含量，有必要对巴戟天叶提取物进行质量控制，以确保其安全性和疗效。
