Danhong Injection combined with t-PA attenuates cerebral ischemia/reperfusion injury and reduces hemorrhagic transformation: association with NF-κB/MMPs signaling
Jinghui Zhang, Chuchu Shan, Zebin Yu, Rui Shi, Changyi Ye, Bin Zhang, Yuyan Zhang, Shan XuAbstract
Objectives
Ischemic stroke, caused by cerebral arterial thrombosis and interrupted blood supply, is a leading cause of brain dysfunction. Tissue plasminogen activator (t-PA) is the standard thrombolytic agent but is limited by hemorrhagic transformation (HT) and blood–brain barrier (BBB) damage. This study explored the beneficial effects of Danhong Injection (DHI, a Traditional Chinese Medicine) as an adjuvant combined with t-PA for the treatment of ischemic stroke.
Methods
Based on cell viability assays, optimal concentrations were 20 μl/ml DHI + 20 μg/ml t-PA. In vitro (mouse brain microvascular endothelial cell, OGD/R model) and in vivo (MCAO rat model) experiments were conducted to assess relevant parameters.
Key findings
In vitro, the combination improved cell morphology, reduced apoptosis, and downregulated phosphorylated NF-κB p65, MMP-2, MMP-9, and hypoxia-inducible factor-1α expression. In vivo, DHI + t-PA decreased P-Selectin, 6-keto-PGF1a, TXA2, PAI-1, MMP-2, and MMP-9 levels, alleviated cerebral infarction and HT, and enhanced neurological recovery.
Conclusions
These protective effects were accompanied by downregulation of the NF-κB/MMPs pathway, suggesting a plausible correlation linked to BBB-related protective phenotypes. Our findings provide preliminary evidence supporting DHI as a promising adjuvant to optimize t-PA-based stroke therapy.