Discovery of Novel 15-Lipoxygenase Activators To Shift the Human Arachidonic Acid Metabolic Network toward Inflammation Resolution

Asthenozoospermia is a common cause of male infertility, the aetiology of which remains unclear in 50–60% of cases. The current study aimed to characterize metabolic alterations in asthenozoospermic seminal plasma and to explore the signalling pathways involved in sperm motility regulation. At first, high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry was used to detect the targeted metabolic network of arachidonic acid (AA). Metabolomic multivariate data analysis showed significant distinction of AA metabolites between asthenozoospermic and healthy seminal plasma. AA as well as its lipoxygenase (LOX) and cytochrome P450 metabolites were found to be abnormally increased, while cyclooxygenase (COX) metabolites were complicatedly disturbed in asthenozoospermic volunteers compared with those in healthy ones. In vitro experiments and western blot analysis of sperm cells revealed a decrease in sperm motility and upregulation of sperm phosphor-P38 induced by AA. P38 inhibitor could increase AA-reduced sperm motility. Also, all the inhibitors of the three metabolic pathways of AA could block AA-induced P38 mitogen-activated protein kinase (MAPK) activation and further improve sperm motility. We report here for the first time that an abnormal AA metabolic network could reduce sperm motility via P38 MAPK activation through the LOX, cytochrome P450 and COX metabolic pathways, which might be an underlying pathomechanism of asthenozoospermia.

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Understanding traditional Chinese medicine anti-inflammatory herbal formulae by simulating their regulatory functions in the human arachidonic acid metabolic network

Molecular BioSystems ◽

10.1039/c3mb25605g ◽

2013 ◽

Vol 9 (7) ◽

pp. 1931 ◽

Cited By ~ 19

Author(s):

Shuo Gu ◽

Ning Yin ◽

Jianfeng Pei ◽

Luhua Lai

Keyword(s):

Arachidonic Acid ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Metabolic Network ◽

Herbal Formulae ◽

Anti Inflammatory ◽

Regulatory Functions

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Diverse Ways of Perturbing the Human Arachidonic Acid Metabolic Network To Control Inflammation

Accounts of Chemical Research ◽

10.1021/acs.accounts.5b00226 ◽

2015 ◽

Vol 48 (8) ◽

pp. 2242-2250 ◽

Cited By ~ 32

Author(s):

Hu Meng ◽

Ying Liu ◽

Luhua Lai

Keyword(s):

Arachidonic Acid ◽

Metabolic Network

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Pharmacodynamics simulation of HOEC by a computational model of arachidonic acid metabolic network

Quantitative Biology ◽

10.1007/s40484-018-0163-4 ◽

2018 ◽

Vol 7 (1) ◽

pp. 30-41

Author(s):

Wen Yang ◽

Xia Wang ◽

Kenan Li ◽

Yuanru Liu ◽

Ying Liu ◽

...

Keyword(s):

Arachidonic Acid ◽

Computational Model ◽

Metabolic Network

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Can Bioactive Lipid Arachidonic Acid Prevent and Ameliorate COVID-19?

Medicina ◽

10.3390/medicina56090418 ◽

2020 ◽

Vol 56 (9) ◽

pp. 418 ◽

Cited By ~ 1

Author(s):

Undurti N. Das

Keyword(s):

Arachidonic Acid ◽

Endothelial Cell ◽

Cell Damage ◽

Vascular Endothelial Cell ◽

M2 Macrophage ◽

Vascular Endothelial ◽

Endothelial Cell Damage ◽

Lipoxin A4 ◽

Inflammation Resolution ◽

Resolution Processes

It is proposed that the bioactive lipid, arachidonic acid (AA, 20:4 n-6), can inactivate severe acute respiratory syndrome(SARS-CoV-2), facilitate M1 and M2 macrophage generation, suppress inflammation, prevent vascular endothelial cell damage, and regulate inflammation resolution processes based on the timely formation of prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) based on the context. Thus, AA may be useful both to prevent and manage coronavrus disease-2019(COVID-19).

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