Danhong Injection combined with t-PA attenuates cerebral ischemia/reperfusion injury and reduces hemorrhagic transformation: association with NF-κB/MMPs signaling

Scritto il 29/10/2026
da Jinghui Zhang

J Pharm Pharmacol. 2026 Oct 1;78(10):rgag129. doi: 10.1093/jpp/rgag129.

ABSTRACT

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.

PMID:42955848 | DOI:10.1093/jpp/rgag129