Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD 4878, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Int J Mol Sci. 2018 Nov 6;19(11):3490. doi: 10.3390/ijms19113490.
Plant-derived compounds that modulate the immune responses are emerging as frontline treatment agents for cancer, infectious diseases and autoimmunity. Herein we have isolated 40 phytochemicals from five Bhutanese medicinal plants-, , , and -and tested 14 purified compounds for their immunomodulatory properties using a murine dendritic cell (DC) line, and cytotoxicity against a human cholangiocyte cell line using xCELLigence real time cell monitoring. These compounds were: pseudaconitine, 14-veratryolpseudaconitine, 14--acetylneoline, linalool oxide acetate, ()-spiroether, luteolin, luteolin-7--β-d-glucopyranoside, protopine, ochrobirine, scoulerine, capnoidine, isomyristicin, bergapten, and isoimperatorin. Of the 14 compounds tested here, scoulerine had adjuvant-like properties and strongly upregulated gene and protein expression whereas bergapten displayed immunosuppressive properties and strongly down-regulated gene and protein expression of MHC-I and other co-stimulatory molecules. Both scoulerine and bergapten showed low cytotoxicity against normal healthy cells that were consistent with their immunoregulatory properties. These findings highlight the breadth of immunomodulatory properties of defined compounds from Bhutanese medicinal plants and show that some of these compounds exert their mechanisms of action by modulating DC activity.
从植物中提取的调节免疫反应的化合物正在成为癌症、传染病和自身免疫性疾病的一线治疗药物。在此，我们从五种不丹药用植物—— 、 、 、 和 中分离出 40 种植物化学物质，并使用小鼠树突状细胞 (DC) 系测试了 14 种纯化化合物的免疫调节特性，使用 xCELLigence 实时细胞监测法测试了它们对人胆管细胞系的细胞毒性。这些化合物包括：乌头碱、14- 香草酰乌头碱、14-乙酰新乌头碱、芳樟醇氧化物乙酸酯、()-螺醚、木犀草素、木犀草素-7-O-β-D-吡喃葡萄糖苷、原阿片碱、奥克布因、苦参碱、可待因、异土木香内酯、补骨脂素和异欧前胡素。在本研究中测试的 14 种化合物中，苦参碱具有佐剂样特性，可强烈上调 基因和蛋白表达，而补骨脂素则表现出免疫抑制特性，可强烈下调 MHC-I 和其他共刺激分子的基因和蛋白表达。苦参碱和补骨脂素对正常健康细胞的细胞毒性均较低，这与其免疫调节特性一致。这些发现强调了来自不丹药用植物的特定化合物具有广泛的免疫调节特性，并表明其中一些化合物通过调节 DC 活性来发挥其作用机制。
