Targeting PDE4B with Ditan Decoction Inhibits Neutrophil Infiltration to Mitigate Neurovascular Unit Injury
10.14148/j.issn.1672-0482.2025.0306
- VernacularTitle:涤痰汤靶向PDE4B减轻卒中后中性粒细胞浸润及神经血管单元损伤
- Author:
Shuhong YU
1
;
Sijie LIU
;
Jiayi ZHU
;
Ling FAN
;
Jiamei GU
;
Hao HUANG
;
Yi LUO
Author Information
1. 苏州市中西医结合医院脑病科,江苏 苏州 215101
- Publication Type:Journal Article
- Keywords:
Ditan Decoction;
neutrophil infiltration;
ischemic stroke;
neurovascular unit;
PDE4B;
myeloperoxidase;
molecular docking
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(3):306-312
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.
