Therapeutic effects of Danhong injection on ischemic stroke recovery: dual modulation of angiogenesis and neurogenesis via activating tyrosine kinase signaling.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Danhong injection (DI), a standardized traditional Chinese medicine injection prepared from Salvia miltiorrhiza Bge. and Carthamus tinctorius L., has been validated in clinical studies for its therapeutic efficacy and is widely used in stroke treatment. However, the exact molecular mechanisms behind its neuroprotective effects during recovery remain unclear. AIM OF THE STUDY: This research aims to evaluate DI's therapeutic potential in promoting functional recovery following cerebral ischemia/reperfusion (CI/R) injury and to uncover the molecular basis of its neuroprotective effects. METHODS: A rat MCAO/R model was established and treated with varying doses (low, medium, high) of DI through tail vein injection over 14 days. Treatment outcomes were assessed via Longa neurological scoring, thermal nociception tests, TTC staining, and histological analysis. Mechanistic studies were conducted using immunohistochemistry, immunofluorescence, and western blotting techniques. RESULTS: Research outcomes showed that DI intervention significantly enhanced neurological performance and thermal sensitivity in CI/R rats, particularly at the 1.0 mL/kg dosage. Histopathological analysis verified DI's capacity to mitigate tissue injury, preserve neuronal integrity, and restore microvascular structure in ischemic cortical regions. Molecular profiling demonstrated that DI boosted angiogenesis via elevated VEGF-A and PDGF-B expression, along with increased CD34endothelial progenitor cells and BrdU/vWFnewborn endothelial cells. DI treatment also elevated populations of Sox2/Nestinneural progenitors and DCX/NeuNnewborn neurons while enhancing tight junction protein ZO-1 expression and ERK1/2 phosphorylation. Furthermore, intraperitoneal co-administration of sunitinib (a specific receptor tyrosine kinase inhibitor) abolished the therapeutic effects of DI, confirming the essential role of receptor tyrosine kinase pathways. CONCLUSIONS: This work reveals that DI administration provides neuroprotection and enhances functional recovery following CI/R injury, with its mechanism of action linked to the promotion of neurovascular regeneration.