Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats
Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2024-12-01
|
| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016424002615 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849309245846061056 |
|---|---|
| author | Wenjie Hu Xueyan Kuang Yao Zhang Yimin Luo Litao Zhang |
| author_facet | Wenjie Hu Xueyan Kuang Yao Zhang Yimin Luo Litao Zhang |
| author_sort | Wenjie Hu |
| collection | DOAJ |
| description | Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (P = 0.0024) and improved the neurobehavioral outcomes (P = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (P = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (P = 0.0018), IL-1β (P = 0.0310), and IL-6 (P = 0.0017), thereby reducing neuronal apoptosis (P = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (P = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation via β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings. |
| format | Article |
| id | doaj-art-1847425438504500a57068d15cc06913 |
| institution | Kabale University |
| issn | 1319-0164 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj-art-1847425438504500a57068d15cc069132025-08-20T03:54:12ZengSpringerSaudi Pharmaceutical Journal1319-01642024-12-01321210221010.1016/j.jsps.2024.102210Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in ratsWenjie Hu0Xueyan Kuang1Yao Zhang2Yimin Luo3Litao Zhang4School of Biological Science, Jining Medical University, Rizhao 276826, Shandong Province, PR ChinaQingdao West Coast New Area Center for Disease Control and Prevention, Qingdao 266427, Shandong Province, PR ChinaSchool of Biological Science, Jining Medical University, Rizhao 276826, Shandong Province, PR ChinaSchool of Biological Science, Jining Medical University, Rizhao 276826, Shandong Province, PR ChinaSchool of Biological Science, Jining Medical University, Rizhao 276826, Shandong Province, PR China; Corresponding author at: School of Biological Science, Jining Medical University, Rizhao 276826, Shandong Province, PR China.Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (P = 0.0024) and improved the neurobehavioral outcomes (P = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (P = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (P = 0.0018), IL-1β (P = 0.0310), and IL-6 (P = 0.0017), thereby reducing neuronal apoptosis (P = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (P = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation via β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings.http://www.sciencedirect.com/science/article/pii/S1319016424002615Phenylacetylglycine (PAGly)Ischemia/Reperfusion Injury (I/R injury)Microgliaβ2-adrenergic Receptors (β2AR)Neuroprotective |
| spellingShingle | Wenjie Hu Xueyan Kuang Yao Zhang Yimin Luo Litao Zhang Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats Saudi Pharmaceutical Journal Phenylacetylglycine (PAGly) Ischemia/Reperfusion Injury (I/R injury) Microglia β2-adrenergic Receptors (β2AR) Neuroprotective |
| title | Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats |
| title_full | Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats |
| title_fullStr | Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats |
| title_full_unstemmed | Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats |
| title_short | Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats |
| title_sort | neuroprotective effects of phenylacetylglycine via β2ar on cerebral ischemia reperfusion injury in rats |
| topic | Phenylacetylglycine (PAGly) Ischemia/Reperfusion Injury (I/R injury) Microglia β2-adrenergic Receptors (β2AR) Neuroprotective |
| url | http://www.sciencedirect.com/science/article/pii/S1319016424002615 |
| work_keys_str_mv | AT wenjiehu neuroprotectiveeffectsofphenylacetylglycineviab2aroncerebralischemiareperfusioninjuryinrats AT xueyankuang neuroprotectiveeffectsofphenylacetylglycineviab2aroncerebralischemiareperfusioninjuryinrats AT yaozhang neuroprotectiveeffectsofphenylacetylglycineviab2aroncerebralischemiareperfusioninjuryinrats AT yiminluo neuroprotectiveeffectsofphenylacetylglycineviab2aroncerebralischemiareperfusioninjuryinrats AT litaozhang neuroprotectiveeffectsofphenylacetylglycineviab2aroncerebralischemiareperfusioninjuryinrats |