Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs (Allium cepa)

doi:10.1016/0090-6980(85)90142-X

Prostaglandins

Volume 29, Issue 5, May 1985, Pages 847-865

Prostaglandins

https://doi.org/10.1016/0090-6980(85)90142-X Get rights and content

Abstract

Two fractions with prostaglandin E-like activity were isolated from onion ( $Allium cepa$ ) by using XAD-2 adsorption, silicic acid column chromatography and thin layer chromatography. The fractions were analyzed by gas chromatography/mass spectrometry and were characterized as isomeric mixtures of 9,10,13-trihydroxy-11-octadecenoic and 9,12,13-trihydroxy-10-octadecenoic acid, which are lipoxygenase metabolites of linoleic acid. Bio-assay, for which cascade superfusion was used and the rabbit coeliac and mesenteric arteries and the rat fundus strip were employed as assay organs, was utilized to monitor the bio-active profile throughout the isolation procedures. The activity of 1 μg of the pharmacologically active fractions T1 and T2 was found to be equivalent to that of respectively 1.33 and 0.63 ng of prostaglandin E₂.

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Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent process
2020, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Citation Excerpt :
The most well-described regioisomers 9,10,13-TriHOME and 9,12,13-TriHOME were first identified by Graveland et al. in 1970, who isolated the TriHOMEs from suspensions of wheat flour [21]. Since then, TriHOMEs have been characterized in several plant systems including potato leaves [22,23], onion bulbs [24] and beetroot [25]. In mammalian systems, attempts have been made to characterize the synthesis of TriHOMEs in porcine leukocytes [26] as well as in fetal calf blood vessels [27].
Trihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived lipid mediators reported to be dysregulated in obstructive lung disease. In contrast to many other oxylipins, TriHOME biosynthesis in humans is still poorly understood. The association of TriHOMEs with inflammation prompted the current investigation into the ability of human granulocytes to synthesize the 16 different 9,10,13-TriHOME and 9,12,13-TriHOME isomers and of the TriHOME biosynthetic pathway. Following incubation with linoleic acid, eosinophils and (to a lesser extent) the mast cell line LAD2, but not neutrophils, formed TriHOMEs. Stereochemical analysis revealed that TriHOMEs produced by eosinophils predominantly evidenced the 13(S) configuration, suggesting 15-lipoxygenase (15-LOX)-mediated synthesis. TriHOME formation was blocked following incubation with the 15-LOX inhibitor BLX-3887 and was shown to be largely independent of soluble epoxide hydrolase and cytochrome P450 activities. TriHOME synthesis was abolished when linoleic acid was replaced with 13-HODE, but increased in incubations with 13-HpODE, indicating the intermediary role of epoxy alcohols in TriHOME formation. In contrast to eosinophils, LAD2 cells formed TriHOMEs having predominantly the 13(R) configuration, demonstrating that there are multiple synthetic routes for TriHOME formation. These findings provide for the first-time insight into the synthetic route of TriHOMEs in humans and expand our understanding of their formation in inflammatory diseases.
Adipose tissue oxylipin profiles vary by anatomical site and are altered by dietary linoleic acid in rats
2019, Prostaglandins Leukotrienes and Essential Fatty Acids
Citation Excerpt :
They are lower in smokers, but elevated in those with chronic obstructive pulmonary disease, and correlate with neutrophil abundance in this disease [45]. They may have a role in skin barrier function [46,47], and have been shown to relax vascular smooth muscle cells in vitro [48]. Further studies are clearly needed to determine which cells in the adipose tissue are producing these enigmatic oxylipins and how they affect adipose functions.
Dietary PUFA and their effects on adipose tissue have been well studied, but oxylipins, the oxygenated metabolites of PUFA, have been sparsely studied in adipose tissue. To determine the oxylipin profile and to examine their potential importance in various adipose sites, female and male rats were provided control, high linoleic acid (LA), or high LA and high α-linolenic acid (LA + ALA) diets for six weeks. Analysis of gonadal (GAT), mesenteric (MAT), perirenal (PAT), and subcutaneous adipose tissues (SAT) revealed higher numbers of oxylipins in MAT and SAT, primarily due to 20–22 carbon cytochrome P450 oxylipins, as well as metabolites of cyclooxygenase derived oxylipins. LA oxylipins made up 75–96% of the total oxylipin mass and largely determined the total relative amounts between depots (GAT > MAT > PAT > SAT). However, when the two most abundant LA oxylipins (TriHOMEs) were excluded, MAT had the highest mass of oxylipins and exhibited the most sex differences. These differences existed despite comparable PUFA composition between depots. Dietary LA increased oxylipins derived from n-6 PUFA, and the addition of ALA generally returned n-6 PUFA oxylipins to levels similar to control and elevated some n-3 oxylipins. These data on oxylipin profiles in adipose depots from different anatomical sites and the effects of diet and sex provide fundamental knowledge that will aid future studies investigating the physiological effects of adipose tissue.
An LC-MS/MS workflow to characterize 16 regio- and stereoisomeric trihydroxyoctadecenoic acids
2018, Journal of Lipid Research
Citation Excerpt :
The enzyme 15-LOX is well-known to enantioselectively hydroxylate linoleic acid at the C-13 position (40, 41), producing only the S-isomer. It is also possible that the observed enantioselectivity could be due to dietary sources because multiple plants produce TriHOMEs enzymatically (9, 12, 13). In conclusion, the current work describes for the first time a straightforward workflow to identify and characterize all 9,10,13-TriHOME and 9,12,13-TriHOME isomers.
Trihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived oxylipins with potential physiological relevance in inflammatory processes as well as in maintaining an intact skin barrier. Due to the high number of possible TriHOME isomers with only subtle differences in their physicochemical properties, the stereochemical analysis is challenging and usually involves a series of laborious analytical procedures. We herein report a straightforward analytical workflow that includes reversed-phase ultra-HPLC-MS/MS for rapid quantification of 9,10,13- and 9,12,13-TriHOME diastereomers and a chiral LC-MS method capable of resolving all sixteen 9,10,13-TriHOME and 9,12,13-TriHOME regio- and stereoisomers. We characterized the workflow (accuracy, 98–120%; precision, coefficient of variation ≤6.1%; limit of detection, 90–98 fg on column; linearity, R² = 0.998) and used it for stereochemical profiling of TriHOMEs in bronchoalveolar lavage fluid (BALF) of individuals with chronic obstructive pulmonary disease (COPD). All TriHOME isomers were increased in the BALF of COPD patients relative to that of smokers (P ≤ 0.06). In both COPD patients and smokers with normal lung function, TriHOMEs with the 13(S) configuration were enantiomerically enriched relative to the corresponding 13(R) isomers, suggesting at least partial enzymatic control of TriHOME synthesis. This method will be useful for understanding the synthetic sources of these compounds and for elucidating disease mechanisms.
Effect of metal ions on the production of isomeric 9,10,13 (9,12,13)-trihydroxy-11E (10E)-octadecenoic acid from linoleic acid by Pseudomonas aeruginosa PR3
2002, Enzyme and Microbial Technology
Hydroxy fatty acids have gained important attentions because of their special properties such as higher viscosity and reactivity compared with other non-hydroxy fatty acids. Previously we reported that a novel bacterial strain Pseudomonas aeruginosa PR3 converted linoleic acid to the equimolar mixture of two compounds, 9,10,13- trihydroxy-11(E)-octadecenoic acid (9,10,13-THOD) and 9,12,13-trihydroxy-10(E)-octadecenoic acid (9,12,13-THOD) which showed anti-fungal activities (Kim, H. Gardner, H.W., Hou, C.T., J. Ind. Microbiol. Biotechnol. 2000, 25, 109–115). In this study we report for the first time the effect of several metal ions as catalytic agents of lipid peroxidation on the production of total THODs by PR3. Among eight different metal ions tested, Fe⁺² and Cu⁺² were effective to produce THODs. However bacterial growth was not significantly affected by the existence of metal ions tested. Fe⁺² ion requirement was specific to THOD production from linoleic acid but not to other incorporation of dihydroxyl group on oleic acid and ricinoleic acid by PR3.
Trihydroxyoctadecadienoic acids exhibit antiatherosclerotic and antiatherogenic activity
1994, Phytomedicine
A standardized mixture of isomeric trihydroxy fatty acids (TFA: 12,13,16-trihydroxy-9Z, 14E-octadecadienoic-, 12,15,16-trihydroxy-9Z, 13E-octadecadienoic-, 9,10,13-trihydroxy-HE, 15Z-octadecadienoic-, and 12,13,16-trihydroxy-9,14Z-octadecadienoic acid), isolated from Bryonia alba L. roots, were found to exhibit antiatherosclerotic (reducing atherosclerotic manifestations) effects as studied in the cell culture obtained from atherosclerotic plaques of the human aorta. TFA, in a concentration range of 10⁻⁸–10⁻⁴ M, reduced the total cholesterol content to a higher extent than nifedipine, and inhibited the [³H]-thymidine incorporation into the cultivated cells. The experiments with deendothelized rabbit aorta also demonstrated that TFA exhibit an antiatherogenic (preventive) effect resulting in a decreased intima thickness and restricted adhesion of blood cells to the surface of the vessel lumen.
Oxylipin pathway to jasmonates: Biochemistry and biological significance
1992, Biochimica et Biophysica Acta - Lipids and Lipid Metabolism

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Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs (Allium cepa)

Abstract

American Pharmacy

Nutrition Research

Biochem. Pharmacol.

Prostaglandins, Leukotrienes and Medicine

Prostaglandins and Medicine

Thrombosis Res.

J. Biol. Chem.

Chem. Phys. Lipids

Prostaglandins

Biochim. Biophys. Acta

Chem. Phys. Lipids

J. Biol. Chem.

Anal. Biochem.

Onions and platelet aggregation

Lancet

Inhibition of platelet aggregation by onion extracts

Lancet

Inhibition of platelet aggregation and thromboxane synthesis by onion and garlic

Lancet

Altered arachidonic acid metabolism in platelets inhibited by onion and garlic extracts

Platelet aggregation inhibitor in garlic

Lancet

Search for prostaglandin A1 in onion

Lipids

Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs ( $Allium cepa$ )

Search for prostaglandin A₁ in onion