Xuan Bi Tong Yu Fang Promotes Angiogenesis via VEGF‐Notch1/Dll4 Pathway in Myocardial Ischemic Rats

Abstract

Objective. To investigate the effect of Xuan Bi Tong Yu Fang (XBTYF) on angiogenesis via the vascular endothelial growth factor- (VEGF-) Notch1/delta-like 4 (Dll4) pathway. Materials and Methods. Sixty Sprague-Dawley rats were randomly divided into six groups: control, sham-operated, myocardial ischemia model, and XBTYF treatment at 3.2, 1.6, and 0.8 g/kg. Electrocardiography was performed to evaluate the successful establishment of the model. Hematoxylin-eosin staining and transmission electron microscopy were carried out to observe the morphology and mitochondrial structure in myocardial cells, respectively. TUNEL staining was performed to assess the degree of cell apoptosis. The expression of VEGF-A, Notch1, Dll4, Bcl2, Bax, caspase 3, caspase 9, and cytochrome-c (Cyt-c) was observed by western blot. Results. XBTYF inhibited changes to the morphology and mitochondrial structure in cardiomyocyte and reduced cell apoptosis. Compared with the model group, XBTYF at all doses (3.2, 1.6, and 0.8 g/kg) reduced the expression of Notch1, Dll4, Bax, caspase 3, caspase 9, and Cyt-c, whereas expression of VEGF-A and Bcl2 was increased. Conclusion. XBTYF attenuated mitochondrial damage and cell apoptosis while promoting the angiogenesis of cardiomyocyte. The associated mechanism may be related to the VEGF-Notch1/Dll4 pathway.

Role of the Notch1 signaling pathway in ischemic heart disease (Review)

“…Some efforts have been made to recognize available inhibitors of Notch1 signaling in ECs. Apart from resveratrol mentioned above (19), it has been shown that Xuan Bi Tong Yu Fang, a well-known traditional Chinese medical prescription, promotes EC-mediated angiogenesis in rats with myocardial ischemia by inhibiting the Dll4/Notch1 pathway (21). The anticoagulant drug, sulodexide (22), and the vasodilator, pentoxifylline (23), have also been found to inhibit the Dll4/Notch1 pathway to affect angiogenesis in mouse proepicardial explant cultures.…”

Therapeutic targets by traditional Chinese medicine for ischemia-reperfusion injury induced apoptosis on cardiovascular and cerebrovascular diseases

“…Danhong injection (DHI) could mitigate inflammation associated with MI through inhibiting NF-κB nuclear translocation and regulating miRNAs, thus improving cardiac function in myocardial infarction rats . Shengmai injection (SMI) could increase cell viability, prevent cell apoptosis, and increase PI3K and p-Akt expression in H9c2 cardiomyocytes injured by doxorubicin (Li et al, 2020c). Furthermore, it has been reported that the SMI-driven reduction in apoptosis was related to the change in the Bcl-2/Bax ratio (Liu et al, 2018a).…”