Carbonized Typhae Pollen coordinates VEGF-dependent hemostatic and vascular protective pathways in blood stasis syndrome.

BACKGROUND

Carbonized Typhae Pollen (CTP) is a class of herbs that resolves blood stasis and stops bleeding. Blood stasis syndrome (BSS) is a pathological state associated with blood circulation disorders and vascular injury, which contributes to the development of cardiovascular diseases. The metabolic microenvironment of endothelial cells (ECs) plays a pivotal role in maintaining vascular homeostasis and is highly sensitive to pathological disturbances. CTP positively enhances the hemostatic phase via the vascular endothelial growth factor (VEGF)/phospholipase C gamma 1 (PLCγ1)/Ca2⁺/cyclooxygenase 2 (COX-2) pathway. Excessive hemostasis may increase the risk of vascular disease. Therefore, the dual pharmacological effect of CTP in achieving "stop bleeding without leaving stasis" implies the involvement of additional regulatory pathways that contribute to vascular protection.

PURPOSE: This study aims to elucidate the protective mechanisms of CTP against BSS-induced circulatory disorders and vascular injury.

METHODS

Models of BSS rats, zebrafish thrombosis model, and hypoxia-induced ECs model were used to evaluate vascular protection. Bioinformatics, metabolomic analyses, and molecular biology studies were integrated to investigate underlying mechanisms.

RESULTS

Treatment with CTP promoted blood circulation, and ameliorated thrombosis in zebrafish. Furthermore, CTP markedly attenuated hypoxia and inflammation caused by blood stasis and facilitated vascular remodeling. Bioinformatics and metabolomic analyses suggested that VEGF and downstream arginine metabolism were key pathways. CTP enhanced vascular protection and promoted remodeling through the VEGF/PI3K/AKT signalling pathway, thereby facilitating vascular repair following injury.

CONCLUSIONS

CTP mediated haemostasis through the VEGF/PLCγ1/Ca²⁺/COX-2 pathway while improving vascular function following haemostasis via the VEGF/PI3K/AKT pathway. These pathways function independently yet remain interconnected, jointly contributing to the vascular homeostasis.