The protective effects of β-caryophyllene on LPS-induced primary microglia M1/M2 imbalance: A mechanistic evaluation
| Autor: | Vahid Reza Askari, Reza Shafiee-Nick |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Microglia Chemistry medicine.medical_treatment Inflammation General Medicine Pharmacology 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Arginase 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system medicine Cannabinoid receptor type 2 lipids (amino acids peptides and proteins) Cannabinoid General Pharmacology Toxicology and Pharmaceutics medicine.symptom Signal transduction Neuroinflammation |
| Zdroj: | Life Sciences. 219:40-73 |
| ISSN: | 0024-3205 |
| Popis: | Aims Neuroinflammation is observed as a routine characterization of neurodegenerative disorders such as dementia, multiple sclerosis (MS) and Alzheimer's diseases (AD). Scientific evidence propounds both of the neuromodulatory and immunomodulatory effects of CB2 in the immune system. β-Caryophyllene (BCP) is a dietary selective CB2 agonist, which deserves the anti-inflammatory and antioxidant effects at both low and high doses through activation of the CB2 receptor. Methods In this study, we investigated the protective effects of a broad range concentration of BCP against LPS-induced primary microglia cells inflammation and M1/M2 imbalance and identifying the portion of the involvement of related signaling pathways on BCP effects using pharmacological antagonists of CB2, PPAR-γ, and sphingomyelinase (SMase). Key findings The protective effects of BCP on LPS-induced microglia imbalance is provided by the M2 healing phenotype of microglia, releasing the anti-inflammatory (IL-10, Arg-1, and urea) and anti-oxidant (GSH) parameters and reducing the inflammatory (IL-1β, TNF-α, PGE2, iNOS and NO) and oxidative (ROS) biomarkers. Moreover, we showed that BCP exerts its effects through CB2 receptors which overproduction of ceramides by SMase at middle to higher concentrations of BCP reduce the protective activity of BCP and results in the activation of the PPAR-γ pathway. Significance In conclusion, the low concentration of BCP has higher selective anti-inflammatory effects rather than high levels. On this occasion, BCP by modulating the microglia is able to have potential therapeutic effects in neuro-inflammation conditions and microglia cells such as MS and AD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect