| Summary: | 碩士 === 元培科技大學 === 生物技術研究所 === 98 === Δ7-eicosatrienoic acid (Δ7-ETrA; Δ7,11,14-20:3), a are polyunsaturated fatty acid (PUFA), is an elongation product of pinolenic acid (PNA; Δ5,9,12-18:3) originally from pine seed oil (PSO). Earlier studies indicated that PNA and its metabolite Δ7-ETrA significantly incorporated and substituted arachidonic acid (AA) in cellular phospholipids, resulting in the reduction of pro-inflammatory prostaglandin E2 (PGE2) synthesis. However, Δ7-ETrA is not commercial available due to limited sources and high production/purification cost, and no studies have been conducted to explore biological effects and possible metabolism to date. In this study, we chemically synthesized, Δ7-ETrA.Using murine macrophage cells as an inflammation model,we determined if Δ7-ETrA can relieve inflammatory response induced by lipopolysaccharide (LPS) through the modulation of cellular PUFA metabolism, pro-inflammatory mediator synthesis,such as nitric oxide (NO), PGE2 and gene expression of inducible nitric oxide synthase (iNOS) and type II cyclooxygenase (COX-2).
Results showed that PNA in PSO could be enriched through the combined techniques of saponification and urea saturation. Then, novel Δ7-ETrA was synthesized and indentified by a series of organic chemical reactions and analysis of gas chromatography (GC)/GC-mas spectrum (GC-MS). The purity of new synthesized Δ7-ETrA was approximate 97% after thin layer chromatography (TLC) separation and the following extraction. Δ7-ETrA significantly reduced concentrations of NO, PGE2 and interleukin-6 (IL-6), but enhanced tumor necrotic fator-α (TNF-α) production. The possible mechanisms involved in the reduction of NO and COX-2 could attribute to the inhibition of iNOS and COX-2 expression. Morevoer, based on results of cellular fatty acid analysis, significant amounts of Δ7-ETrA substituting for AA in the phospholipids might also play an important role.
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