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Protocatechuic aldehyde prevents ischemic injury by attenuating brain microvascular endothelial cell pyroptosis via
Yan Guo1, Jie-Hong Yang1, Yu He2
1College of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
Background:
Pyroptosis is a pro-inflammatory cell death characterized by the formation of inflammasomes. Abnormal inflammation in brain microvascular endothelial cells (BMECs) has been correlated with ischemic stroke. Protocatechuic aldehyde (PCA) is a hydrophilic phenolic acid derived from the traditional Chinese herb Salvia miltiorrhiza with significant anti-inflammatory effects. However, the mechanism of PCA on BMEC pyroptosis under ischemic injury has been largely unexplored.
Purpose:
We aimed to study the effects and mechanism of PCA on BMEC pyroptosis under ischemic injury.
Methods:
Sprague-Dawley (SD) rats were injected through the tail vein with different concentrations of PCA after transient middle cerebral artery occlusion (MCAO) was performed. The protective effects of PCA in SD rats were examined via neurological scores, infarct volume evaluation, and anti-pyroptosis effects using immunofluorescence staining and western blot. Rat BMECs (rBMECs) were treated with different concentrations of PCA after oxygen and glucose deprivation (OGD). The ability of PCA to protect rBMECs was examined via cell viability, anti-oxidative activity, and anti-pyroptosis effects as determined by qRT-PCR and western blot. Additionally, the role of lncRNA Xist in anti-pyroptosis responses of PCA-treated rBMECs was validated with lncRNA Xist siRNA.
Results:
We found that treatment with MCAO and OGD increased the expression of NOD-like receptor protein 3, gasdermin D, Caspase-1, interleukin-1β, and NIMA-related kinase 7, which was reversed by treatment with PCA or MCC950 (a pyroptosis inhibitor). In addition, PCA reduced the cerebral infarct volume in MCAO rats and promoted cell survival and proliferation in OGD/reperfusion-treated rBMECs. PCA enhanced the antioxidant activity and mitochondrial membrane potential in rBMECs. PCA also enhanced lncRNA Xist expression, and when the expression of lncRNA Xist was silenced, PCA could not alleviate pyroptosis well in rBMECs.
Conclusion:
Protocatechuic aldehyde prevents ischemic injury by attenuating rBMEC pyroptosis via lncRNA Xist.
Insights
Protocatechuic aldehyde (PCA) prevents ischemic stroke by reducing brain microvascular endothelial cell pyroptosis. This protective effect is mediated through the long non-coding RNA Xist, highlighting a novel therapeutic pathway.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Pyroptosis, a pro-inflammatory cell death, is implicated in ischemic stroke due to abnormal inflammation in brain microvascular endothelial cells (BMECs).
- Protocatechuic aldehyde (PCA), derived from Salvia miltiorrhiza, exhibits anti-inflammatory properties, but its mechanism in BMEC pyroptosis during ischemic injury remains unclear.
Purpose of the Study:
- To investigate the effects of PCA on BMEC pyroptosis under ischemic conditions.
- To elucidate the underlying molecular mechanisms, including the role of lncRNA Xist.
Main Methods:
- In vivo studies involved inducing ischemic injury in rats (MCAO) and administering PCA, followed by assessments of neurological scores and infarct volume.
- In vitro studies used oxygen-glucose deprivation (OGD) on rat BMECs (rBMECs) treated with PCA, evaluating cell viability, oxidative activity, and pyroptosis markers.
- The role of lncRNA Xist was assessed using siRNA in PCA-treated rBMECs.
Main Results:
- PCA treatment reversed the upregulation of pyroptosis markers (NLRP3, GSDMD, Caspase-1, IL-1β, NEK7) in both MCAO rats and OGD-treated rBMECs.
- PCA reduced cerebral infarct volume, enhanced rBMEC survival, proliferation, and antioxidant capacity, and preserved mitochondrial membrane potential.
- PCA upregulated lncRNA Xist expression, and silencing lncRNA Xist diminished PCA's protective effects against pyroptosis.
Conclusions:
- Protocatechuic aldehyde effectively attenuates BMEC pyroptosis and mitigates ischemic injury.
- The protective mechanism of PCA involves the upregulation of lncRNA Xist, offering a potential therapeutic target for ischemic stroke.
