Departamento de Química, Universidad Nacional de Colombia, Cra, 30 N degrees 45 -03, Bogotá D,C, Colombia.
J Inflamm (Lond). 2009 Mar 10;6:5. doi: 10.1186/1476-9255-6-5.
We are reporting for the first time the in vivo anti-inflammatory activity of extracts and fractions, and in vitro anti-inflammatory activity of pure compounds, all isolated from Pseudopterogorgia elisabethae collected at the Providencia (chemotype 1) and San Andrés (chemotype 2) Islands (SW Caribbean).
Extracts from P. elisabethae were fractionated on silica gel to yield fractions: F-1 (pseudopterosins PsQ, PsS and PsU) and F-2 (amphilectosins A and B, PsG, PsK, PsP and PsT and seco-pseudopterosins seco-PsJ and seco-PsK) from chemotype 1, and F-3 (elisabethatrienol, 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (interconverting mixture) and amphilecta-8(13),11,14-triene-9,10-dione) from chemotype 2. By using preparative RP-HPLC and spectroscopic means, we obtained the pure PsG, PsK, PsP, PsQ, PsS, PsT, PsU, seco-PsK and the interconverting mixture of non-glycosylated diterpenes (IMNGD). The anti-inflammatory properties of extracts and fractions were evaluated using in vivo model "12-O-tetradecanoyl-phorbol-acetate (TPA)-induced mouse ear oedema". The activities of pure compounds and of the IMNGD were evaluated using in vitro assays myeloperoxidase (MPO) release (by human polymorphonuclear neutrophils (PMNs)), nitric oxide release (by J-774 cells) and scavenger activity on NO.
In the in vivo anti-inflammatory assay, extracts and F-3 showed low inhibition levels of inflammation compared to indomethacin, F-1 and F-2. Additionally, we evaluated the MPO release to the inflammation site, and found a marked inhibition of MPO levels by all extracts and fractions, even superior to the inhibition shown by indomethacin.Furthermore, in the MPO in vitro assay, IMNGD, PsQ, PsS, PsT and PsU, exhibited higher inhibition levels compared to dexamethasone and indomethacin. In the NO release in vitro, IMNGD, PsP and PsT were the most potent treatments. Finally, because the PsG, PsP and seco-PsK did not exhibit any NO scavenger activity, they should inhibit the inducible Nitric Oxide Synthase (iNOS) or other routes that influence this enzyme. Alternatively, PsQ, PsS, and PsU did show scavenger activity.
All results presented contribute to demonstrate that the compounds isolated in this work from P. elisabethae are promising molecules with an interesting anti-inflammatory activity profile. Additionally, the results obtained could provide preliminary insights towards their structure-activity relationship.
我们首次报道了从采集自普罗维登西亚岛（化学型 1）和圣安德烈斯岛（化学型 2）的伊丽莎白假珊瑚（Pseudopterogorgia elisabethae）中分离得到的提取物和馏分的体内抗炎活性，以及纯化合物的体外抗炎活性。
从 P. elisabethae 中提取的物质经硅胶柱层析分离得到 F-1（伪珊瑚素 PsQ、PsS 和 PsU）和 F-2（ Amphilectosins A 和 B、PsG、PsK、PsP 和 PsT 以及 seco-伪珊瑚素 seco-PsJ 和 seco-PsK）来自化学型 1，和 F-3（elisabethatrienol、10-acetoxy-9-hydroxy- 和 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes（互变异构混合物）和 amphilecta-8(13)、11、14-triene-9、10-dione）来自化学型 2。通过使用制备型 RP-HPLC 和光谱手段，我们获得了纯 PsG、PsK、PsP、PsQ、PsS、PsT、PsU、secopseudopterosin 和非糖基化二萜互变异构混合物（IMNGD）。使用体内模型“12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的小鼠耳水肿”评估提取物和馏分的抗炎特性。使用体外测定法（人多形核白细胞（PMN）中髓过氧化物酶（MPO）释放）和一氧化氮（NO）释放（J-774 细胞）以及对 NO 的清除活性来评估纯化合物和 IMNGD 的活性。
在体内抗炎测定中，与吲哚美辛相比，提取物和 F-3 对炎症的抑制水平较低。此外，我们评估了 MPO 向炎症部位的释放，发现所有提取物和馏分均显著抑制 MPO 水平，甚至优于吲哚美辛的抑制作用。此外，在体外 MPO 测定中，IMNGD、PsQ、PsS、PsT 和 PsU 表现出比地塞米松和吲哚美辛更高的抑制水平。在体外 NO 释放中，IMNGD、PsP 和 PsT 是最有效的治疗方法。最后，由于 PsG、PsP 和 seco-PsK 没有表现出任何 NO 清除活性，它们应该抑制诱导型一氧化氮合酶（iNOS）或影响该酶的其他途径。或者，PsQ、PsS 和 PsU 确实表现出清除活性。
所有呈现的结果都有助于证明从 P. elisabethae 中分离得到的化合物是具有有趣抗炎活性特征的有前途的分子。此外，获得的结果可以为它们的结构-活性关系提供初步见解。
