摘要
目的:考察药用辅料聚乙二醇400(PEG400)对黄芩苷药代动力学及抗炎作用的影响,利用分子对接技术初步探讨黄芩苷及其主要代谢物黄芩素6-O-β-D-葡萄糖醛酸苷(B6G)的抗炎作用。方法:大鼠随机分为2组,分别以水和PEG400为溶解基质,给大鼠灌胃相等剂量的黄芩苷水溶液(黄芩苷+水组)与黄芩苷PEG400溶液(黄芩苷+PEG400组),不同时间段血浆样品经处理后,利用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定大鼠血浆中黄芩苷及其主要代谢物B6G的浓度,运用DAS 3.2.2软件处理药代动力学参数;将小鼠随机分为空白组(生理盐水,20 mL·kg^(-1)),阿司匹林组(0.2 g·kg^(-1)),黄芩苷/黄芩苷+PEG400高、低剂量(3.0,1.5 g·kg^(-1))组,连续给药7 d,建立小鼠耳肿胀及足肿胀模型,计算肿胀度及肿胀抑制率。结果:药代动力学研究结果显示,与黄芩苷+水组相比,大鼠灌胃黄芩苷PEG400溶液后黄芩苷及B6G的血药浓度增加,药时曲线下面积(AUC0-t)分别提高了2.36,1.97倍,药峰浓度(Cmax)分别提高了2.12,1.65倍;小鼠耳肿胀和足肿胀炎症模型结果表明,小鼠灌胃黄芩苷PEG400溶液后抗炎效果增强。此外,分子对接结果表明黄芩苷与B6G可以与多靶点蛋白[肿瘤坏死因子(TNF)-α,白细胞介素(IL)-6,IL^(-1)β,前列腺素E2(PGE2),核转录因子-κB(NF-κB)]位点结合,具有较高亲和力,且优于阳性药阿司匹林。结论:PEG400可提高黄芩苷及其主要代谢物B6G的血药浓度,且抗炎效果增强,黄芩苷与B6G可以与多种炎症因子及核转录因子靶点蛋白形成较强的氢键,推测黄芩苷及B6G共同发挥了抗炎作用。
Objective: To investigate the effects of polyethylene glycol 400(PEG400) on the pharmacokinetics and anti-inflammatory effect of baicalin,and to preliminarily explore the anti-inflammatory effects of baicalin and its main metabolite baicalein 6-O-β-D-glucuronide(B6 G) by molecular docking.Method:Rats were randomly divided into two groups with water and PEG400 as the dissolving matrix,and rats were administrated the equal dose of baicalin aqueous solution(baicalin+water group)and baicalin PEG400 solution(baicalin+PEG400 group). After the plasma samples were processed at different time periods,the concentrations of baicalin and B6 G in rat plasma were determined by ultra performance liquid chromatographytandem mass spectrometry(UPLC-MS/MS),and pharmacokinetic parameters were processed by DAS 3.2.2 software. Mice were randomly divided into a blank group(normal saline,20 mL·kg^(-1)),aspirin group(dose of0.2 g·kg^(-1)), baicalin/baicalin+PEG400 high and low dose(3.0, 1.5 g·kg^(-1)) groups, after continuous administration for 7 days,the mouse ear swelling and foot swelling models were established,and the swelling degree and swelling inhibition rate were calculated. Result: The pharmacokinetic study showed that compared with baicalin+water group,the plasma concentrations of baicalin and B6 G increased after administration of baicalin PEG400 solution,and the area under the curve(AUC0-t)increased by 2.36,1.97 times,and the peak concentration(Cmax)increased by 2.12,1.65 times,respectively. The results of mouse ear and foot swelling inflammation models showed that the anti-inflammatory effect was enhanced after intragastric administration of baicalin PEG400 solution. In addition,molecular docking results showed that baicalin and B6 G could site bind to multiple target proteins[tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL^(-1)β,prostaglandin E2(PGE2)and nuclear transcription factor-κB(NF-κB)] with higher affinity,which was superior to the positive drug aspirin. Conclusion: PEG400 can increase the plasma concentr
作者
杨七妹
周明皓
王鹏娇
曹思源
张硕
杨盛刚
张敏
高秀丽
YANG Qi-mei;ZHOU Ming-hao;WANG Peng-jiao;CAO Si-yuan;ZHANG Shuo;YANG Sheng-gang;ZHANG Min;GAO Xiu-li(State Key Laboratory of Functions and Applications of Medicinal Plants,School of Pharmaceutical Sciences,Engineering Center of Microbiology and Biochemical Pharmacy,Experimental Animal Center,Guizhou Medical University,Guiyang 550025,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第22期131-138,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81160413)
贵州省教育厅项目(黔科合KY字[2019]009)。
