The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat
The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat
复制标题
黄芩苷、黄芩素及其联合用药对溃疡性结肠炎大鼠的治疗作用及机制比较研究
DOI：
10.3389/fphar.2019.01466
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发表时间：
2019-12-13
影响因子：
5.6
通讯作者：
Ren, Yongshen
中科院分区：
文献类型：
--
作者：
Liang, Shuai;Deng, Xin;Ren, Yongshen
前言：溃疡性结肠炎（UC）是一种发病率高、治疗困难的炎症性肠病。最近，在肠道疾病，特别是UC的治疗中，已经通过单独或组合使用药物黄芩苷和黄芩素取得了显著进展。然而，黄芩苷、黄芩素及其联合治疗UC的疗效和作用机制尚未完全阐明。材料与方法：我们构建了一个UC大鼠模型，该模型包含多种复杂因素，包括高糖高脂饮食、高温高湿环境（HTHE）、过量饮酒和大肠杆菌感染。然后用黄芩苷、黄芩素或两者的组合治疗模型大鼠。结果如下：结果显示黄芩苷、黄芩素和联合治疗在治疗UC中的疗效显著差异，以及通过核因子-κB和MAPK途径抑制炎症的差异。如上所述建立UC大鼠模型。然后，用黄芩苷（100 mg kg-1）、黄芩素（100 mg kg-1）或两者（100 mg kg-1，黄芩苷：黄芩素= 4：1/1：1）处理大鼠7天。观察临床症状和体征、体温、器官指数、组织病理学、血液生化和代谢产物，比较治疗效果和UC指标。黄芩苷、YSR（幼黄芩苷与黄芩素之比）、黄芩素、WSR（枯黄芩苷与黄芩素之比）在临床症状和体征、体温、脏器指数、血清炎性细胞因子水平、血液生化及主要脏器组织病理学变化方面均有显著性差异，其中YSR的治疗效果最好。采用LC-MS/MS检测黄芩苷、黄芩素或两者转化为6种代谢产物：黄芩苷、汉黄芩苷、乳清素A、黄芩素、汉黄芩素和乳清素A。在不同处理条件下，6种代谢物的水平在大肠、小肠和肺中存在显著差异，但在血液中无差异。六种代谢物的水平在大肠、小肠和肺中有显著差异，但在血清中无显著差异。结论：提示黄芩苷和黄芩素应更准确地应用于特定疾病，尤其是黄芩苷或黄芩苷含量高的黄芩在治疗UC时应优先使用。
Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated. Materials and Methods: we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of Escherichia coli. Model rats were then treated with baicalin, baicalein, or a combination of the two. Results: The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation via the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg-1), baicalein (100 mg kg-1), or both (100 mg kg-1, baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young Scutellaria baicalensis ratio of baicalin and baicalein), baicalein, and WSR (Withered Scutellaria baicalensis ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum. Conclusion: All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in Scutellaria baicalensis (Tiaoqin) should be preferred in treatment of UC.