Robust inhibitory effects of conjugated linolenic acids on a cyclooxygenase-related linoleate 10S-dioxygenase: Comparison with COX-1 and COX-2

Abstract

There are many reports of the anti-inflammatory, anti-cancer, and anti-atherosclerotic activities of conjugated linolenic acids (cLNA). They constitute a small percentage of fatty acids in the typical human diet, although up to 80% of the fatty acids in certain fruits such as pomegranate. In the course of studying a bacterial fatty acid dioxygenase (Nostoc linoleate 10S-DOX, an ancient relative of mammalian cyclooxygenases), we detected strong inhibitory activity in a commercial sample of linoleic acid. We identified two cLNA isomers, β-eleostearic (9E,11E,13E-18:3) and β-calendic acid (8E,10E,12E-18:3), as responsible for that striking inhibition with a Ki of ~49 nM and ~125 nM, respectively, the most potent among eight cLNA tested. We also examined the effects of all eight cLNA on the activity of COX-1 and COX-2. Jacaric acid (8Z,10E,12Z-18:3) and its 12E isomer, 8Z,10E,12E-18:3, strongly inhibit the activity of COX-1 with a Ki of ~1.7 and ~1.1 μM, respectively. By contrast, COX-2 was ≤ 30% inhibited at 10μM concentrations of the cLNA. Identifying the activities of the naturally occurring fatty acids is of interest in terms of understanding their interaction with the enzymes, and for explaining the mechanistic basis of their biological effects. The study also highlights the potential presence of inhibitory fatty acids in commercial lipids prepared from natural sources. Analysis of seven commercial samples of linoleic acid by HPLC and UV spectroscopy is illustrated as supplementary data.

Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions

“…Conjugated fatty acids exert many highly beneficial effects, including reduction of adiposity, improved insulin sensitivity, reduced carcinogenesis, and reduced atherosclerosis (reviewed in [ 170 ]). CLAs and CLnAs act via PPAR-γ (reviewed in [ 171 ]), PPAR-α [ 172 ], and inhibition of cyclooxygenases and lipoxygenases [ 173 , 174 ]. Whether typical intestinal microbiota generate sufficient CLA/CLnA to exert the extraintestinal effects seen with CLA/CLnA supplementation is unclear, as feeding essential fatty acids increases gut but not circulating levels of CLAs and CLnAs [ 164 ].…”

Pomegranate Seed Oil and Bitter Melon Extract Affect Fatty Acids Composition and Metabolism in Hepatic Tissue in Rats

“…There is an evidence that the conjugated linolenic acids exhibit potent anti-inflammatory activity, which results both from a decrease in AA transformation and the inhibition of pro-inflammatory cytokines such as TNF-α, or IL-6 [ 32 ]. Mashhadi et al [ 33 ] showed the reduction in the PGE 2 level as a result of CLnA treatment. Those authors proved that the above-mentioned dependence is related to the inhibition of both COX-1 and COX-2.…”

Bitter Gourd and Pomegranate Seed Oils as Sources of α-Eleostearic and Punicic Acids: Purification and IIAntioxidant Properties in Cell Lines

“…The isolation of the α-eleostearic and punicic acids was performed by using the Semi-Preparative System. The confirmation of these components was conducted by High-Performance Liquid Chromatography (HPLC), when coupled with a mass spectrometer [8]. The cell viabilities were executed with the CLNAs that were isolated from the BSO and PSO seeds, at different concentrations and with a 24 hours exposure.…”