Tongqiao huoxue decoction and its components promote angiogenesis and treat ischemic stroke via glycolysis-enhanced VEGF-A/VEGFR2 pathway.

BACKGROUND

Tongqiao Huoxue Decoction (TQHXD), a representative Traditional Chinese Medicine (TCM) formula, is known for its effects in revitalizing the brain, opening the orifices, promoting blood circulation, and resolving stasis. It is widely used to treat stroke and related disorders.

OBJECTIVE

This study aimed to investigate the effects of TQHXD and its component groups on post-ischemic angiogenesis in rats and to elucidate the underlying mechanisms.

METHODS

Permanent middle cerebral artery occlusion (pMCAO) was performed in rats. Therapeutic effects of TQHXD were observed on days 1, 3, 5, and 7 post-surgery. Neurological deficits, infarct volume, cerebral edema, cortical cell morphology, and neuronal damage were assessed. Microvascular endothelial cells (CD31 + ) in the ischemic cortex were also evaluated. TQHXD was separated into two sub-formulas: Tongqiao Tongyang Group (TQTY) and Huoxue Huayu Group (HXHY). Drug efficacy was assessed using laser speckle contrast imaging for cerebral blood flow, and glycolysis-related markers were measured. Immunostaining was used to assess endothelial cell proliferation and vascular maturation. Protein levels were evaluated by Western blotting.

RESULTS

TQHXD alleviated neurological deficits, reduced infarct volume, and improved the cellular morphology in the infarcted cortex of rats with MCAO rats on days 1, 3, 5, and 7. It promotes angiogenesis, manifested as a significant increase in CD31 + endothelial cells on day 7. TQHXD and its components markedly improved cerebral blood flow, increased blood perfusion velocity, and restored perfusion homogeneity in the MCAO rats. What's more, TQHXD and HXHY enhanced glycolytic activity in endothelial cells, and promoted angiogenesis and vascular maturation. These effects were associated with the upregulation of key signaling molecules, including VEGF-A/VEGFR2, p-PI3K/PI3K, p-AKT/AKT, p-PLCγ1/PLCγ1, and p-ERK1/2/ERK1/2.

CONCLUSION

TQHXD and HXHY promote angiogenesis and treat ischemic stroke (IS) by activating the VEGF-A/VEGFR2-PI3K/AKT and VEGF-A/VEGFR2-PLCγ1/ERK1/2 pathways through enhanced glycolysis.