Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F.!Vill
Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F.!Vill
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DOI：
10.1248/bpb.25.1049
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发表时间：
2002-08-01
影响因子：
2
通讯作者：
Noguchi, H
中科院分区：
文献类型：
--
作者：
Kobayashi, W;Miyase, T;Noguchi, H
已提出脯氨酰内肽酶（PEP，EC 3.4.21.26）在降解参与学习和记忆过程的含脯氨酸的神经肽中起作用，例如，加压素、P物质和促甲状腺激素释放激素（TRH）。在寻找药用植物活性成分的过程中，我们研究了乌药根中的PEP抑制成分。VILL和分离出两种已知的单宁，表儿茶素（1）和七叶单宁B（2），以及四种已知的倍半萜，林德烯（3），林德烯乙酸酯（4），林德内酯（5）和异林德内酯（6）作为抑制剂。化合物1、2、4对脑膜炎黄杆菌PEP酶的抑制作用强于对大鼠脑组织PEP酶的抑制作用。然而，化合物3、5和6对两种来源的酶的抑制程度相同，而且化合物6是对来自大鼠脑上清液的PEP的最强天然抑制剂。动力学研究表明，化合物1、2为非竞争性抑制剂，化合物3-6为竞争性抑制剂。这是从天然药物中分离出的第一个显示出显著竞争抑制活性的非酚类成分的例子。
Prolyl endopeptidase (PEP, EC 3.4.21.26) has been proposed to play a role in degradation of proline-containing neuropeptides involved in the processes of learning and memory, e.g., vasopressin, substance P, and thyrotropin-releasing hormone (TRH). In the course of our search for bioactive constituents in medicinal plants, we studied the PEP inhibitory constituents of the roots of Lindera strychnifolia F. VILL and isolated two known tannins, epicatechin (1) and aesculitannin B (2), and four known sesquiterpenes, linderene (3), linderene acetate (4), linderalactone (5) and isolinderalactone (6) as inhibitors. On the inhibitory activities of six compounds against PEP from Flavobacterium meningosepticum and that from rat brain supernatant, compounds 1, 2 and 4 inhibited the enzyme from Flavobacterium more strongly than that from rat brain supernatant. However, compounds 3, 5 and 6 inhibited the enzymes from both origins to the same extent and furthermore, compound 6 was the strongest natural inhibitor against PEP from rat brain supernatant. The kinetic study of these inhibitors indicated that compounds 1, 2 are noncompetitive inhibitors and compounds 3-6 are competitive inhibitors. This is the first example of non-phenolic constituents showing significant competitive inhibitory activity being isolated from natural medicines.