ArticleDrug design, development and therapy2016
Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury.
Article in Drug design, development and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Investigating the In Vitro Mitochondria-Mediated Anticancer Activity of the Plant Metabolite Ursolic Acid.International journal of molecular sciences · 2026Article
- Recent developments on ursolic acid and its potential biological applications.Toxicology reports · 2025Review
- Effect of bisphenol A on the neurological system: a review update.Archives of toxicology · 2024Review
- Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways.Biomedicines · 2023Review
- Ursolic Acid Ameliorated Neuronal Damage by Restoring Microglia-Activated MMP/TIMP Imbalance in vitro.Drug design, development and therapy · 2023Article
- The Signaling Pathways and Targets of Natural Compounds from Traditional Chinese Medicine in Treating Ischemic Stroke.Molecules (Basel, Switzerland) · 2022Review
- Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments.PPAR research · 2022Review
- Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases.International journal of molecular sciences · 2021Review
- Ursolic and Oleanolic Acids: Plant Metabolites with Neuroprotective Potential.International journal of molecular sciences · 2021Review
- Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches.International journal of molecular sciences · 2020Review
- Transcriptional activation of antioxidant gene expression by Nrf2 protects against mitochondrial dysfunction and neuronal death associated with acute and chronic neurodegeneration.Experimental neurology · 2020Review
- Ocimum basilicum attenuates ethidium bromide-induced cognitive deficits and pre-frontal cortical neuroinflammation, astrogliosis and mitochondrial dysfunction in rats.Metabolic brain disease · 2020Article
- Repeated dose (90 days) oral toxicity study of ursolic acid in Han-Wistar rats.Toxicology reports · 2020Article
- Network Pharmacology-Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood-Brain Barrier.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Association betweenNeural regeneration research · 2019Article
- Ursolic Acid and Its Derivatives as Bioactive Agents.Molecules (Basel, Switzerland) · 2019Review
- Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression.Oxidative medicine and cellular longevity · 2019Review
- Ursolic acid in health and disease.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Review
- Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury PossiblyFrontiers in neurology · 2018Article
- Therapeutic Potential of Ursolic Acid to Manage Neurodegenerative and Psychiatric Diseases.CNS drugs · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance.
methodsThe middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed.
resultsUA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01). Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01) but an increased level of TIMP1 (P<0.01). UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a significant but partial neuroprotective effect.
conclusionUA can act as a PPARγ agonist to improve the metalloprotease/anti-metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent.
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