Anti-migraine effect of wine-processed Radix scutellariae: Pharmacodynamic verification in nitroglycerin-induced rats and correlation study between compounds dissolution and the fractal dimension

Abstract Ethnopharmacological relevance Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear. Aim of the study To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory. Materials and methods In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV–Vis spectrophotometry and HPLC separately. Results The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p   fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r  Conclusions Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.