Hanáková Zuzana, Hošek Jan, Kutil Zsófia, Temml Veronika, Landa Přemysl, Vaněk Tomáš, Schuster Daniela, Dall'Acqua Stefano, Cvačka Josef, Polanský Ondřej, Šmejkal Karel
Laboratory of Plant Biotechnologies, Institute of Experimental Botany, The Czech Academy of Sciences , 16502 Prague, Czech Republic.
Department of Pharmaceutical and Pharmacological Sciences, University of Padua , 35131 Padua, Italy.
J Nat Prod. 2017 Apr 28;80(4):999-1006. doi: 10.1021/acs.jnatprod.6b01011. Epub 2017 Mar 21.
Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.
香叶基黄酮已作为可能开发为抗炎剂的化合物进行了研究。从毛泡桐果实中分离出一系列天然香叶基黄烷酮，并对这些化合物的抗炎活性及其可能的作用机制进行了研究。鉴定出两种新化合物[泡桐酮C（17）和毛泡双黄酮O（20）]，并对所有分离的衍生物抑制环氧化酶（COX-1和COX-2）和5-脂氧合酶（5-LOX）的能力进行了测定。所测试的化合物表现出不同程度的活性，其中几种化合物的活性与COX-1、COX-2和5-LOX测定中使用的标准品相当或更高。然而，与布洛芬相比，只有化合物毛泡双黄酮O（20）对COX-2比对COX-1表现出更高的选择性。对接研究支持了测试化合物与上述酶相互作用的能力，该研究揭示了所选测试物质可能纳入这些酶的活性位点。此外，对COX/LOX双重抑制剂之一双黄酮（14）（毛泡桐的一种主要香叶基黄烷酮）进行了体外研究，以获得其对脂多糖处理的THP-1巨噬细胞炎症影响的蛋白质组学概况，支持其先前观察到的抗炎活性并揭示其抗炎作用机制。
