Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells,Journal of Ethnopharmacology

当前位置： X-MOL 学术 › J. Ethnopharmacol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells
Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2023-02-20 , DOI: 10.1016/j.jep.2023.116278
Chao Meng ₁ , Lanping Zhong ₁ , Ting Lu ₁ , Qi Gu ₁ , Xinyue Du ₁ , Fanglan Liu ₂ , Chunhua Xia ₂

Affiliation

Ethnopharmacological relevance

Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear.

Aim of the study

We purposed to explore OCT2-mediated interactions and compatibility mechanisms of the main active compounds in SMF.

Materials and methods

Fifteen active ingredients of SMF, including ginsenoside Rb1, Rd, Re, Rg1, Rf, Ro and Rc, methylophiopogonanone A and B, ophiopogonin D and Dˊ, schizandrin A and B, schizandrol A and B, were selected to investigate OCT2-mediated interactions in Madin-Darby cacine kidney (MDCK) cells stably expressing OCT2.

Results

Among the above 15 main active components, only ginsenosides Rd, Re and schizandrin B could significantly inhibit the uptake of 4-(4-(dimethylamino)styryl)-N-methyl pyridiniumiodide (ASP⁺), a classical substrate of OCT2. Ginsenoside Rb1 and methylophiopogonanone A can be transported by MDCK-OCT2 cells, and their uptake was significantly reduced when OCT2 inhibitor decynium-22 was added. Ginsenoside Rd could remarkably reduce the uptake of methylophiopogonanone A and ginsenoside Rb1 by OCT2, ginsenoside Re only decreased the uptake of ginsenoside Rb1, while schizandrin B had no effect on the uptake of both.

Conclusions

OCT2 mediates the interaction of the major active components in SMF. Ginsenosides Rd, Re and schizandrin B are the potential inhibitors of OCT2, while ginsenosides Rb1 and methylophiopogonanone A are the potential substrates of OCT2. There is an OCT2-mediated compatibility mechanism among these active ingredients of SMF.

中文翻译：

生脉方的复杂成分与MDCK细胞中的有机阳离子转运蛋白2（OCT2）相互作用

民族药理学相关性

生脉方（SMF）是一种著名的中草药复方制剂，广泛用于治疗心肌缺血、心律失常等危及生命的疾病。我们之前的研究表明，SMF中的一些活性成分可以与有机阴离子转运多肽1B1（OATP1B1）、乳腺癌抗性蛋白（BCRP）和有机阴离子转运蛋白1（OAT1）等有机阳离子转运蛋白2（OCT2）相互作用是肾脏中高表达的摄取转运蛋白，其与 SMF 中主要活性成分的相互作用仍不清楚。

研究目的

我们旨在探索 OCT2 介导的相互作用和 SMF 中主要活性化合物的相容性机制。

材料和方法

选择 SMF 的 15 种活性成分，包括人参皂苷 Rb1、Rd、Re、Rg1、Rf、Ro 和 Rc、甲基麦冬酮 A 和 B、麦冬甙 D 和 Dˊ、五味子 A 和 B、五味子醇 A 和 B，以研究 OCT2 介导的相互作用在稳定表达 OCT2 的 Madin-Darby 肾 (MDCK) 细胞中。

结果

在上述 15 种主要活性成分中，只有人参皂苷 Rd、Re 和五味子乙素能显着抑制OCT2 的经典底物4-(4-(二甲氨基)苯乙烯基)-N-甲基碘化吡啶 (ASP + ) 的摄取^。人参皂苷 Rb1 和甲基麦冬酮 A 可由 MDCK-OCT2 细胞转运，加入 OCT2 抑制剂 decynium-22 后，它们的摄取显着降低。人参皂苷Rd可显着降低OCT2对甲基麦冬酮A和人参皂苷Rb1的摄取，人参皂苷Re仅降低人参皂苷Rb1的摄取，而五味子乙素对两者的摄取均无影响。