Ursolic acid promotes microglial polarization toward the M2 phenotype via PPARγ regulation of MMP2 transcription

Wang, Yuye; Qiu, Luying; Deng, Shumin; Liu, Fang; He, Zishu; Li, Mengye; Wang, Yanzhe

doi:10.1016/j.neuro.2023.04.001

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…Notably, those effects were not observed in the case of the co-addition of UA and the potent selective PPARγ antagonist GW9662. In a word, UA protects against neuro-inflammation through the PPARγ pathway, opening the way for its application in ischemic stroke therapy [110].…”

Section: Ua Effect On Pparγmentioning

confidence: 99%

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

Kadasah,

Radwan

2023

Biomedicines

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Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury. In fact, PTs share a common lipophilic structure that resembles NRs’ endogenous ligands. Herein, we present a review of the literature on UA’s effect on NRs, showcasing the resulting health benefits and potential therapeutic outcomes. De facto, UA exhibited numerous pharmacodynamic effects on PPAR, LXR, FXR, and PXR, resulting in remarkable anti-inflammatory, anti-hyperlipidemic, and hepatoprotective properties, by lowering lipid accumulation in hepatocytes and mitigating non-alcoholic steatohepatitis (NASH) and its subsequent liver fibrosis. Furthermore, UA reversed valproate and rifampicin-induced hepatic lipid accumulation. Additionally, UA showed great promise for the treatment of autoimmune inflammatory diseases such as multiple sclerosis and autoimmune arthritis by antagonizing RORγ. UA exhibited antiproliferative effects against skin, prostate, and breast cancers, partially via PPARα and RORγ pathways. Herein, for the first time, we explore and provide insights into UA bioactivity with respect to NR modulation.

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Section: Ua Effect On Pparγmentioning

confidence: 99%

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

Kadasah,

Radwan

2023

Biomedicines

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“…The dual specificity protein kinase-phosphatase-1 (DUSP1), also known as mitogen-activated protein kinase-phosphatase-1 (MKP-1), is a negative regulatory factor on the activation of mitogen activated protein kinases (MAPKs) (15). DUSP1 are expressed widely in the brain, including PFC (16).…”

Section: Introductionmentioning

confidence: 99%

The DUSP1 on CaMKII-positive neurons in mPFC mediates adolescent cocaine exposure-induced higher sensitivity to cocaine during adulthood

Wei

Cheng

Chen

et al. 2022

Preprint

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Cocaine abuse during adolescence increases the risk for developing drug addiction in later life, but the underlying molecular mechanism remains unclear. Here, adolescent cocaine-exposed (ACE) male mice models were established by giving once-daily intraperitoneal injections of 15 mg/kg cocaine to mice during adolescence (P28-P42). We found that ACE mice exhibited a higher sensitivity to subthreshold dose of cocaine (1 mg/kg) in adulthood, accompanied with triggered activities and dendritic spine density of pyramidal neuron, increased Dusp1 gene, as well as reduced protein levels and activity of dual specificity phosphatase 1 (DUSP1) in mPFC. Specific overexpression of DUSP1 on mPFC glutamatergic neurons efficiently blocked cocaine-preferred behaviors and reduced mPFC activity, while knockdown of DUSP1 maintained cocaine-preferred behaviors and increased mPFC activity in ACE mice. MAPK-related signals, especially ERK1/2, might underlie the mediating effects of DUSP1. Collectively, these findings suggested that targeting mPFC DUSP1 may represent a promising therapeutic strategy for the treatment and attenuation of addiction susceptibility, particularly in addicts with a history of adolescent drugs exposure.

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Ursolic acid promotes microglial polarization toward the M2 phenotype via PPARγ regulation of MMP2 transcription

Cited by 2 publications

References 47 publications

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

Overview of Ursolic Acid Potential for the Treatment of Metabolic Disorders, Autoimmune Diseases, and Cancers via Nuclear Receptor Pathways

The DUSP1 on CaMKII-positive neurons in mPFC mediates adolescent cocaine exposure-induced higher sensitivity to cocaine during adulthood

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