摘要
该研究旨在以人源结肠癌细胞Caco-2细胞为模型,研究龙血竭酚类提取物中8个主要成分在Caco-2细胞中的吸收特性,初步阐明龙血竭酚类提取物的口服吸收机制。采用UPLC-MS/MS同时测定龙血竭酚类提取物中紫草黄酮、7,4′-二羟基黄酮、7,4′-二羟基-5-甲氧基高异黄烷酮、7,4′-二羟基高异黄烷酮、龙血素C、龙血素A、龙血素B和紫檀茋8种主要成分,在Caco-2细胞中分别考察不同孵育时间、浓度、温度、P-gp抑制剂、MRP抑制剂、OCTN1抑制剂、OCTN2抑制剂对龙血竭主要成分细胞摄取的影响,并通过转运试验测定8种主要成分的表观渗透系数Papp及转运速率,预测龙血竭提取物口服吸收机制。结果显示,龙血竭酚类提取物中8种主要成分的细胞摄取具有时间依赖性和浓度依赖性,且各成分的摄取均不需要消耗能量,符合被动扩散过程;P-gp抑制剂、MRP抑制剂和OCTN1抑制剂对各主要成分的细胞摄取量均无影响,仅OCTN2抑制剂的加入显著降低了紫檀茋的摄取量(P<0.05);转运结果中,8种成分的流出率ER均<1.5。说明龙血竭酚类提取物中8种主要成分的吸收机制可能为被动扩散,且紫檀茋可能是OCTN2的底物。
The purpose of this study was to study the absorption characteristics of eight main components from dragon′s blood phenolic extracts in Caco-2 cells based on the humancolon cancer cell Caco-2 model, and to clarify the oral absorption mechanism of such phenolic extracts. UPLC-MS/MS was used in this study to determine the content of 8 active ingredients including thevetiaflavone, 7,4′-dihydroxyflavone, 7,4′-dihydroxy-5-methoxyhomoisoflavanone, 7,4′-dihydroxyhomoisoflavanone, loureirin C, loureirin A, loureirin B and pterostilbene from dragon′s blood phenolic extracts, and Caco-2 cells were used to investigate the effects of incubation time, concentration, temperature, P-gp inhibitor, MRP inhibitor, OCTN1 inhibitor and OCTN2 inhibitor on the absorption of each component. In addition, the transport experiment was conducted to measure the apparent permeability coefficient Papp and transport rate of the eight main components to predict the oral absorption mechanism of dragon′s blood phenolic extracts. The experimental results showed that the cell uptake of the eight main components in dragon′s blood phenolic extracts was time-dependent and concentration dependent, and the uptake of each component did not need to consume energy, which was consistent with the passive diffusion process. P-gp inhibitor, MRP inhibitor and OCTN1 inhibitor had no effect on the cell uptake of each component, only the addition of OCTN2 inhibitor significantly reduced the uptake of pterostilbene(P<0.05). In the transport results, the ER values of the outflow rates of the eight components were all less than 1.5. The above results show that the absorption mechanism of the eight components in Draconis resina phenolic extract may be passive diffusion, and pterostilbene may be the substrate of OCTN2.
作者
张馨
王莉芳
陈佳琪
邹博林
陈秀红
李军
屠鹏飞
王金铃
ZHANG Xin;WANG Li-fang;CHEN Jia-qi;ZOU Bo-lin;CHEN Xiu-hong;LI Jun;TU Peng-fei;WANG Jin-ling(Modern Research Center for Traditional Chinese Medicine,School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2020年第20期4889-4895,共7页
China Journal of Chinese Materia Medica
基金
北京中医药大学杰出青年人才项目(BUCM-2019-JCRC003)
中华中医药学会青年人才托举工程项目[CACM-2018-(QNRC2-C04)]。
