Discovery and identification of proangiogenic chemical markers from Gastrodiae Rhizoma based on zebrafish model and metabolomics approach

Introduction Angiogenesis is closely related to a variety of diseases, and therapies based on angiogenesis are intensely investigated. Studies have shown that the use of Gastrodiae Rhizoma (GR, Gastrodia elata) can benefit the treatment of ischemic cardiovascular diseases and atherosclerosis by stimulating angiogenesis. Objective This study tested the angiogenesis effects of a group of chemical markers isolated from GR. Material and methods Zebrafish model was used to evaluate angiogenesis by setting four groups: blank control group, model group, positive control group and treatment group (0.1, 1, and 100 mu g/mL RGP). The Gray correlation analysis (GCA) was implemented to calculate the correlation coefficients of each compound between the peak area in liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) and the bioactivity, the top ten components with the correlation degree > 0.9 were listed. Results and discussion The optimum final concentration of GR on proangiogenesis effect was determined to be 100 mu g/mL. Ten compounds, including gastrodin, parishin E, stigmasterol, p-hydroxybenzyl alcohol, citric acid, etc., were identified to have high correlation coefficients with proangiogenic activity. Furthermore, the network pharmacologic analysis of these compounds revealed that the compounds systematically regulate the formation of new blood vessels via networked vital targets and signalling pathways. Conclusion GR can promote the growth of blood vessels, ten chemical components discovered contribute to this proangiogenesis activity. These chemical markers of GR thus provide a foundation for further studies on medicinal substances and quality evaluation of GR, also providing a scientific basis for modern interpretation of the processing theory of traditional Chinese medicine.