Buxue Yimu Pills improve angiogenesis and blood flow in experimental zebrafish and rat models

J Ethnopharmacol. 2022 May 10:289:115002. doi: 10.1016/j.jep.2022.115002. Epub 2022 Jan 20.

Abstract

Ethnopharmacological relevance: Buxue Yimu Pills (BYP) is a well-known traditional Chinese medicine prescription which is clinical used in gynecology and obstetrics, and is documented to exhibit therapeutic potential to defective angiogenesis and impaired blood flow.

Aim of the study: This study aimed to investigate the effects and biological mechanisms of BYP in improvement of defective angiogenesis and impaired blood flow which represent major health issues associated with various diseases including postpartum or abortion complications.

Materials and methods: In this study, VEGFR tyrosine kinase inhibitor II (VRI) was used to establish blood vessel loss model in Tg(fli-1a:EGFP) zebrafish embryos. Blood vessel loss was calculated, and quantitative real-time PCR (qRT-PCR) assay was performed to detect gene expression. Mifepristone and misoprostol were applied to construct a medical-induced incomplete abortion rats model. Whole blood viscosity indexes, hemorheology and coagulation function of the rats were investigated. Immunohistochemistry analysis was used for evaluation of the uterine tissues.

Results: BYP treatment significantly promoted angiogenesis as evidenced by the restoration of VRI-induced blood vessel loss in zebrafish embryos. BYP treatment effectively reversed VRI-induced down-regulation of the VEGFRs (Kdr, Kdrl and Flt1). Furthermore, BYP administration significantly suppressed the increase of whole blood viscosity indexes, and remarkably shortened the levels of prothrombin time and activated partial thromboplastin time in the medical-induced incomplete abortion rats, indicating the improvement of hemorheology and coagulation function. Immunohistochemistry analysis suggested that BYP administration increased the expression level of VEGFR2 in uterus tissues of the rats.

Conclusion: BYP exhibits therapeutic effects in promoting angiogenesis and blood circulation, and mitigating blood stasis, supporting its clinical application for postpartum or abortion complications.

Keywords: Angiogenesis; Blood flow; Buxue Yimu Pills; Medical abortion rats; Zebrafish.

MeSH terms

  • Abortion, Incomplete / drug therapy
  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Zebrafish
  • Zebrafish Proteins / genetics

Substances

  • Angiogenesis Inducing Agents
  • Drugs, Chinese Herbal
  • Zebrafish Proteins
  • Kdr protein, rat
  • Vascular Endothelial Growth Factor Receptor-2
  • kdr protein, zebrafish