Liu Weijun, Wei Ling, Kanai Yoshikatsu, He Xin
Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin 300100, China.
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China.
Evid Based Complement Alternat Med. 2021 Oct 5;2021:8351717. doi: 10.1155/2021/8351717. eCollection 2021.
and are an incompatible herbal pair in the traditional Chinese medicine theory "eighteen incompatible medicaments," and they should not be used simultaneously in clinical treatment for safety. This study aimed to investigate the incompatibility mechanism between and based on their interaction with P-glycoprotein (P-gp). The interaction between and during decocting as well as absorption was investigated by determining the dry extract yield and by rat single-pass intestinal perfusion (SPIP) model. Inhibition of different species of on P-gp function was examined using the SPIP model. The mRNA and protein expression of P-gp was determined by PCR and western blotting. The active ingredients of were predicted and screened for inhibiting P-gp activity by Schrodinger's molecular docking and MDR1-MDCK cell transport study, respectively. Mediation of monoester alkaloids in by P-gp was predicted and examined using Schrodinger's molecular docking and SPIP experiment, respectively. In the results, when was combined with , the toxic ingredient benzoylmesaconine in displayed higher intestinal permeability, whereas the toxic ingredients showed no significant difference during the decoction process. inhibited both the P-gp function and expression; in contrast, inhibited the function only. Alkaloids including peimine, peimisine, and imperialine were the active ingredients for inhibiting P-gp activity. Benzoylmesaconine in was the substrate of P-gp.
在传统中医理论“十八反”中，[药材名称1]与[药材名称2]是相反的药对，为安全起见，临床治疗中不应同时使用。本研究旨在基于[药材名称1]与[药材名称2]与P-糖蛋白（P-gp）的相互作用来研究它们的相反机制。通过测定干浸膏得率以及采用大鼠单通道肠灌注（SPIP）模型，研究了[药材名称1]与[药材名称2]在煎煮过程中的相互作用以及[药材名称1]的吸收情况。使用SPIP模型检测了不同种类的[药材名称1]对P-gp功能的抑制作用。通过PCR和蛋白质印迹法测定P-gp的mRNA和蛋白表达。分别通过薛定谔分子对接和MDR1-MDCK细胞转运研究预测并筛选了[药材名称1]中抑制P-gp活性的活性成分。分别通过薛定谔分子对接和SPIP实验预测并检测了P-gp对[药材名称1]中单酯生物碱的介导作用。结果显示，当[药材名称1]与[药材名称2]合用时，[药材名称1]中的毒性成分苯甲酰新乌头碱表现出更高的肠道通透性，而在[药材名称1]的煎煮过程中，毒性成分无显著差异。[药材名称1]抑制P-gp功能和表达；相比之下，[药材名称2]仅抑制功能。包括贝母碱、浙贝母碱和西贝母碱在内的生物碱是抑制P-gp活性的活性成分。[药材名称1]中的苯甲酰新乌头碱是P-gp的底物。
