Oxylipins from the microalgae Chlamydomonas debaryana and Nannochloropsis gaditana and their activity as TNF-α inhibitors.
The chemical study of the microalgae Chlamydomonas debaryana and Nannochloropsis gaditana has led to the isolation of oxylipins. The samples of C. debaryana have yielded the compounds (4Z,7Z,9E,11S,13Z)-11-hydroxyhexadeca-4,7,9,13-tetraenoic acid (1), (4Z,7E,9E,13Z)-11-hydroxyhexadeca-4,7,9,13-tetraenoic acid (2), (4Z,6E,10Z,13Z)-8-hydroxyhexadeca-4,6,10,13-tetraenoic acid (3), (4Z,8E,10Z,13Z)-7-hydroxyhexadeca-4,8,10,13-tetraenoic acid (4), and (5E,7Z,10Z,13Z)-4-hydroxyhexadeca-5,7,10,13-tetraenoic acid (5), which are derived from the fatty acid 16:4Δ(4,7,10,13) together with the compound (5Z,9Z,11E,15Z)-13-hydroxyoctadeca-5,9,11,15-tetraenoic acid (7) derived from coniferonic acid (18:4Δ(5,9,12,15)). In addition, the known polyunsaturated hydroxy acids 11-HHT (6), (5Z,9Z,11E)-13-hydroxyoctadeca-5,9,11-trienoic acid (8), (13S)-HOTE (9), (9E,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (10), 9-HOTE (11), 12-HOTE (12), 16-HOTE (13) and (13S)-HODE (14) have also been obtained. The chemical study of N. gaditana has led to the isolation of the hydroxy acid (15S)-HEPE (15) derived from EPA (20:5Δ(5,8,11,14,17)). The structures of the isolated compounds were established by spectroscopic means. The optical activity displayed by oxylipins 1, 2, 6, 7, 9, 10, 14, and 15 suggests the occurrence of LOX-mediated pathways in C. debaryana and N. gaditana. In anti-inflammatory assays, all the tested compounds inhibited the TNF-α production in LPS-stimulated THP-1 macrophages. The most active oxylipin was the C-16 hydroxy acid 1, which at 25μM caused a 60% decrease of the TNF-α level.
Departamento de Química Orgánica, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain.
Carolina
C
de Los Reyes
Departamento de Biología Vegetal y Ecología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
Javier
J
Ávila-Román
Departamento de Química Orgánica, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain.
María J
MJ
Ortega
Instituto Tecnológico de Canarias, Playa de Pozo Izquierdo, 35119 Santa Lucía-Gran Canaria, Spain.
Adelina
A
de la Jara
Departamento de Biología Vegetal y Ecología, Facultad de Biología, Universidad de Sevilla, 41012 Sevilla, Spain.
Sofía
S
García-Mauriño
Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
Virginia
V
Motilva
Departamento de Química Orgánica, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain. Electronic address: eva.zubia@uca.es.
Eva
E
Zubía
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation; D002470:Cell Survival; D002696:Chlamydomonas / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015394:Molecular Structure; D054883:Oxylipins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D058009:Stramenopiles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D054883:Oxylipins; D014409:Tumor Necrosis Factor-alpha
Anti-inflammatory activity; Chlamydomonaceae; Chlamydomonas debaryana; Eustigmataceae; Nannochloropsis gaditana; Oxylipins; Polyunsaturated hydroxy acids; TNF-α inhibition