ArticleProceedings of the National Academy of Sciences of the United States of America2020
A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 103 citations in OpenAlex.
- Targeting C/EBPβ/ Calbindin 1 pathway bolsters the neural resilience to tau pathology and improves tau-impaired episodic memory.Molecular psychiatry · 2026Article
- Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An Insight into Molecular Mechanisms and Therapeutic Approaches.Molecular neurobiology · 2026Review
- Plasticity, injury-induced reprogramming, and translational applications of Schwann cells in neural regeneration.Frontiers in cellular neuroscience · 2026Review
- Ursolic acid derivatives improved clinical signs of experimental autoimmune encephalomyelitis by modulating central nervous system inflammation.Metabolic brain disease · 2025Article
- Exploring the neuroprotective benefits of phytochemicals extracted from indigenous edible fruits in Bangladesh.Animal models and experimental medicine · 2025Review
- Lysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.Molecular biology reports · 2025Article
- Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor.Frontiers in immunology · 2025Review
- Impact of calcitriol and PGDDrug delivery and translational research · 2024Article
- Brain-targeted ursolic acid nanoparticles for anti-ferroptosis therapy in subarachnoid hemorrhage.Journal of nanobiotechnology · 2024Article
- [Ursolic acid improved demyelination and interstitial fluid drainage disorders in schizophrenia mice].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss.Military Medical Research · 2024Article
- Article
- Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.Journal of neuroinflammation · 2024Article
- Deciphering Neuroprotective Effect ofCurrent drug targets · 2024Review
- Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice.The journal of venomous animals and toxins including tropical diseases · 2024Article
- FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment.Cell death & disease · 2023Article
- Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways.Biomedicines · 2023Review
- Glia Signaling and Brain Microenvironment in Migraine.Molecular neurobiology · 2023Review
- Plausibility of natural immunomodulators in the treatment of COVID-19-A comprehensive analysis and future recommendations.Heliyon · 2023Review
- High-throughput screening for myelination promoting compounds using human stem cell-derived oligodendrocyte progenitor cells.iScience · 2023Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Current multiple sclerosis (MS) medications are mainly immunomodulatory, having little or no effect on neuroregeneration of damaged central nervous system (CNS) tissue; they are thus primarily effective at the acute stage of disease, but much less so at the chronic stage. An MS therapy that has both immunomodulatory and neuroregenerative effects would be highly beneficial. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that ursolic acid (UA), an antiinflammatory natural triterpenoid, also directly promotes oligodendrocyte maturation and CNS myelin repair. Oral treatment with UA significantly decreased disease severity and CNS inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Importantly, remyelination and neural repair in the CNS were observed even after UA treatment was started on day 60 post immunization when EAE mice had full-blown demyelination and axonal damage. UA treatment also enhanced remyelination in a cuprizone-induced demyelination model in vivo and brain organotypic slice cultures ex vivo and promoted oligodendrocyte maturation in vitro, indicating a direct myelinating capacity. Mechanistically, UA induced promyelinating neurotrophic factor CNTF in astrocytes by peroxisome proliferator-activated receptor γ(PPARγ)/CREB signaling, as well as by up-regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation. Together, our findings demonstrate that UA has significant potential as an oral antiinflammatory and neural repair agent for MS, especially at the chronic-progressive stage.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.