ArticleCell death & disease2013
Inhibition of 12/15-lipoxygenase by baicalein induces microglia PPARβ/δ: a potential therapeutic role for CNS autoimmune disease.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis.EBioMedicine · 2018Trial
- Lipoxygenase (LOX) signaling in epilepsy: Pathophysiology and therapeutic prospects.Neurobiology of disease · 2026Review
- From Demyelination to Intervention: Natural Compounds as Emerging Therapeutic Targets in Multiple Sclerosis Neuroinflammation.Journal of immunology research · 2026Review
- Article
- Voluntary exercise alleviates neural functional deficits in Parkinson's disease mice by inhibiting microglial ferroptosis via SLC7A11/ALOX12 axis.NPJ Parkinson's disease · 2025Article
- Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored inAntioxidants (Basel, Switzerland) · 2025Review
- Baicalein improves motor dysfunction and cognitive impairment while promoting remyelination in an animal model of multiple sclerosis through the antioxidant mechanism.Frontiers in pharmacology · 2025Article
- Phytochemical-mediated efferocytosis and autophagy in inflammation control.Cell death discovery · 2024Review
- The Effect of the Extraction Conditions on the Antioxidant Activity and Bioactive Compounds Content in Ethanolic Extracts ofMolecules (Basel, Switzerland) · 2024Article
- Targeting ferroptosis with the lipoxygenase inhibitor PTC-041 as a therapeutic strategy for the treatment of Parkinson's disease.PloS one · 2024Article
- Mitigating neurodegenerative diseases: the protective influence of baicalin and baicalein through neuroinflammation regulation.Frontiers in pharmacology · 2024Review
- Natural products targeting cellular processes common in Parkinson's disease and multiple sclerosis.Frontiers in neurology · 2023Review
- Male infertility and somatic health - insights into lipid damage as a mechanistic link.Nature reviews. Urology · 2022Review
- Lipoxygenase Metabolism: Critical Pathways in Microglia-mediated Neuroinflammation and Neurodevelopmental Disorders.Neurochemical research · 2022Review
- PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.Cancer letters · 2022Article
- PPARβ/δ Augments IL-1β-Induced COX-2 Expression and PGE2 Biosynthesis in Human Mesangial Cells via the Activation of SIRT1.Metabolites · 2022Article
- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- P. aeruginosa augments irradiation injury via 15-lipoxygenase-catalyzed generation of 15-HpETE-PE and induction of theft-ferroptosis.JCI insight · 2022Article
- Scutellaria baicalensis georgi is a promising candidate for the treatment of autoimmune diseases.Frontiers in pharmacology · 2022Review
- Cepharanthine Attenuates Early Brain Injury after Subarachnoid Hemorrhage in Mice via Inhibiting 15-Lipoxygenase-1-Mediated Microglia and Endothelial Cell Ferroptosis.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
12/15-Lipoxygenase (12/15-LO) is an enzyme that converts polyunsaturated fatty acids into bioactive lipid derivatives. In this study, we showed that inhibition of 12/15-LO by baicalein (BA) significantly attenuated clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Inhibited migration of autoimmune T cells into the central nervous system (CNS) by BA treatment could be attributed to reduced activation of microglia, which was indicated by suppressed phagocytosis, and decreased production of proinflammatory cytokines and chemokines in the CNS. We further observed that inhibition of 12/15-LO with BA led to increased expression of peroxisome proliferator-activated receptor (PPAR)β/δ in microglia of EAE mice. This was confirmed in vitro in primary microglia and a microglia cell line, BV2. In addition, we demonstrated that BA did not affect 12/15-LO or 5-lipoxygenase (5-LO) expression in microglia, but significantly decreased 12/15-LO products without influencing the levels of 5-LO metabolites. Moreover, among these compounds only 12/15-LO metabolite 12-hydroxyeicosatetraenoic acid was able to reverse BA-mediated upregulation of PPARβ/δ in BV2 cells. We also showed that inhibition of microglia activation by PPARβ/δ was associated with repressed NF-κB and MAPK activities. Our findings indicate that inhibition of 12/15-LO induces PPARβ/δ, demonstrating important regulatory properties of 12/15-LO in CNS inflammation. This reveals potential therapeutic applications for MS.
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