a Faculty of Pharmaceutical Sciences , University of Iceland , Reykjavik , Iceland.
b Department of Immunology , Landspitali - The National University Hospital of Iceland , Reykjavik , Iceland.
Pharm Biol. 2017 Dec;55(1):2116-2122. doi: 10.1080/13880209.2017.1373832.
Halichondria (Halichondriidae) marine sponges contain components possessing various biological activities, but immunomodulation is not among the ones reported.
This study evaluated the immunomodulatory effects of fractions/compounds from Halichondria sitiens Schmidt.
Crude dichloromethane/methanol extracts of H. sitiens were subjected to various chromatographic techniques to obtain fractions/compounds with immunomodulatory activity, using bioassay-guided isolation. The effects of the fractions/compounds were determined by measuring secretion of cytokines and expression of surface molecules by dendritic cells (DCs) and their ability to stimulate and modify cytokine secretion by allogeneic CD4 T cells. The bioactive fractions were chemically analyzed to identify the immunomodulatory constituents by 1D, 2D NMR, and HRMS data.
Several lipophilic fractions from H. sitiens at 10 μg/mL decreased secretion of the pro-inflammatory cytokines IL-12p40 and IL-6 by the DCs, with maximum inhibition being 64% and 25%, respectively. In addition, fractions B3b3F and B3b3J decreased the ability of DCs to induce T cell secretion of IFN-γ. Fraction B3b3 induced morphological changes in DCs, characterized by extreme elongation of dendrites and cell clustering. Chemical screening revealed the presence of glycerides and some minor unknown constituents in the biologically active fractions. One new glyceride, 2,3-dihydroxypropyl 2-methylhexadecanoate (1), was isolated from one fraction and two known compounds, 3-[(1-methoxyhexadecyl)oxy]propane-1,2-diol (2) and monoheptadecanoin (3), were identified in another, but none of them had immunomodulatory activity.
These results demonstrate that several lipophilic fractions from H. sitiens have anti-inflammatory effects on DCs and decrease their ability to induce a Th1 type immune response.
藤壶（藤壶科）海洋海绵含有具有各种生物活性的成分，但免疫调节作用不在其中。
本研究评估了来自藤壶（H. sitiens）的化合物的免疫调节作用。
藤壶粗二氯甲烷/甲醇提取物通过各种色谱技术进行分离，采用生物测定指导分离，获得具有免疫调节活性的化合物。通过测量树突状细胞（DC）细胞因子的分泌和表面分子的表达以及它们刺激和改变同种异体 CD4 T 细胞细胞因子分泌的能力来确定化合物的作用。对生物活性化合物进行化学分析，通过 1D、2D NMR 和 HRMS 数据鉴定免疫调节成分。
H. sitiens 的几种亲脂性部位在 10 μg/mL 时降低了 DC 细胞因子 IL-12p40 和 IL-6 的分泌，最大抑制率分别为 64%和 25%。此外，部位 B3b3F 和 B3b3J 降低了 DC 诱导 T 细胞分泌 IFN-γ的能力。部位 B3b3 诱导 DC 形态发生变化，表现为树突极度伸长和细胞聚集。化学筛选显示生物活性部位存在甘油酯和一些未知的次要成分。一种新的甘油酯，2,3-二羟丙基 2-甲基十六烷酸酯（1），从一个部位分离出来，两个已知的化合物，3-[(1-甲氧基十六烷基)氧基]丙烷-1,2-二醇（2）和单十七烷酸（3），从另一个部位鉴定出来，但它们都没有免疫调节活性。
这些结果表明，H. sitiens 的几种亲脂性部位对 DC 具有抗炎作用，并降低了它们诱导 Th1 型免疫反应的能力。
