School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, JS, 210009, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
J Ethnopharmacol. 2020 Dec 5;263:113131. doi: 10.1016/j.jep.2020.113131. Epub 2020 Jul 28.
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.
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.
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.
The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution.
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.
ethnopharmacological 相关性:酒制黄芩(RS)是黄芩的炮制产品,黄芩是黄芩的干燥根。中药方剂中有记载,酒制 RS 具有抗偏头痛的作用,但作用尚未得到证实,其可能的机制尚不清楚。
验证酒制 RS 对硝酸甘油(NTG)诱导大鼠偏头痛的抗偏头痛作用,并基于分形理论探讨化合物溶解与孔隙结构的相关性。
在药效学验证中,首先通过观察大鼠抓头次数评价酒制 RS 对偏头痛的影响,然后通过 ELISA 和免疫组化评估测定 NTG 诱导大鼠模型中一氧化氮(NO)、降钙素基因相关肽(CGRP)和 c-Fos 的水平来研究。在相关性研究中,将 RS 的炒制时间设置为 5min、10min 和 15min。扫描电子显微镜(SEM)和压汞法用于探索孔隙结构和主要参数,包括孔径分布、孔体积、孔隙率、表面积和分形维数。采用紫外可见分光光度法和 HPLC 法分别测定总黄酮和五种主要成分(包括黄芩素、黄芩苷、黄芩素、汉黄芩素和汉黄芩苷)的化合物溶解情况。
动物实验表明,与模型组相比,酒制 RS 能显著减少 NTG 诱导大鼠模型的抓头次数(p<0.01),显著降低 NO(p<0.01)、CGRP(p<0.05)和 c-Fos 的水平(p<0.01)。结果表明,酒处理会通过改变 RS 的孔隙结构影响化合物的溶解。孔隙结构参数与化合物溶解之间呈正相关的顺序为总表面积>分形维数(r>0),呈负相关的顺序为平均孔径>总孔隙率>总体积(r<0)。与其他样品组相比(p<0.05),炒制 10min 的酒制 RS 具有更有利于化合物溶解的孔隙结构。
酒炮制通过改变 RS 的孔隙结构增强 RS 的抗偏头痛作用,这与化合物的溶解有关。炒制 10min 的 RS 可能更有利于治疗偏头痛。