Isogarcinol is a new immunosuppressant.
Isogarcinol is a new immunosuppressant.
复制标题
异藤黄醇是一种新型免疫抑制剂
DOI：
10.1371/journal.pone.0066503
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Cen J;Shi M;Yang Y;Fu Y;Zhou H;Wang M;Su Z;Wei Q
钙调磷酸酶（calcalineurin， CN）是一种独特的蛋白磷酸酶，在免疫调节中起着重要作用。本研究以CN为靶酶，对山竹藤黄中一系列天然化合物的免疫抑制特性进行了研究，发现了一种活性化合物异氨基酚。酶促试验表明异氨基酚以剂量依赖的方式抑制CN。浓度相对较低的异丙二醇可显著抑制豆豆蛋白A （ConA）和混合淋巴细胞反应（MLR）诱导的小鼠脾t淋巴细胞增殖。此外，它在小鼠急性毒性试验和口服给药方面的表现比环孢素A （CsA）好得多，对实验动物的不良反应少，毒性低。小鼠口服异丙二醇可导致异基因皮肤移植中延迟型超敏反应（DTH）的剂量依赖性降低和移植物存活时间延长。这些发现提示异肌醇可作为一种新的口服免疫调节药物预防移植排斥反应，并可作为自身免疫性疾病的长期用药。
Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. In this study we used CN as a target enzyme to investigate the immunosuppressive properties of a series of natural compounds from Garcinia mangostana L., and discovered an active compound, isogarcinol. Enzymatic assays showed that isogarcinol inhibited CN in a dose-dependent manner. At concentrations resulting in relatively low cytotoxicity isogarcinol significantly inhibited proliferation of murine spleen T-lymphocytes induced by concanavalin A (ConA) and the mixed lymphocyte reaction (MLR). In addition, it performed much better in acute toxicity tests and via oral administration in mice than cyclosporin A (CsA), with few adverse reactions and low toxicity in experimental animals. Oral administration of isogarcinol in mice resulted in a dose-dependent decrease in delayed type hypersensitivity (DTH) and prolonged graft survival in allogeneic skin transplantation. These findings suggest that isogarcinol could serve as a new oral immunomodulatory drug for preventing transplant rejection, and for long-term medication in autoimmune diseases.