Chen Yang, Zhang Fan, Ren Wenjing, Zhou Yue, Jiang Shiru, Zhang Shuo, Xu Gui, Ge Xiutong, Gao Hui
School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, China.
Front Pharmacol. 2025 Apr 7;16:1558298. doi: 10.3389/fphar.2025.1558298. eCollection 2025.
This study elucidated the potential mechanisms by which Phellodendri Chinensis Cortex with salt-water processing (SPC) enhances renal targeting efficacy, through investigating the effects of Phellodendri Chinensis Cortex (PC) on renal uptake and efflux transport capabilities before and after salt-water processing.
This study employed molecular docking, UPLC-TDQ-MS/MS, BCA, Western Blotting, and RT-PCR to assess the effects of raw Phellodendri Chinensis Cortex (RPC), SPC, berberine (BBR), and berberrubine (BBRR) on the transport capacity and expression of renal transport proteins OAT1, OAT3, OCT2, MATE1, MATE2K, P-gp, and MRP2 in HEK-293 cells.
Analyses demonstrated that BBR and BBRR exhibited a strong affinity for OCT2, P-gp, MRP2. Compared to RPC, SPC can increase the uptake capacity and expression of OCT2, while it can decrease efflux capacity and expression of P-gp and MRP2. Simultaneously, BBRR showed similar effects on OCT2, P-gp, and MRP2, compared to BBR. Therefore, the enhanced renal targeting effect of SPC can be attributed to the differential impact of the partial conversion of BBR to BBRR on the transport capacity of the renal transporters OCT2, P-gp, and MRP2.
This study investigated the interactions between renal transporter proteins and drugs, with the objective of elucidating the mechanism by which SPC enhances renal targeting efficacy. The findings of this study offer new insights and methodologies for exploring the effects of Processing of Chinese Materia Medica (PCMM) on the meridian tropism of other traditional Chinese medicines (TCMs).
本研究通过考察盐炙黄柏（SPC）炮制前后对肾脏摄取和外排转运能力的影响，阐明了盐炙黄柏增强肾脏靶向作用的潜在机制。
本研究采用分子对接、超高效液相色谱-串联四极杆飞行时间质谱（UPLC-TDQ-MS/MS）、BCA法、蛋白质免疫印迹法（Western Blotting）和逆转录聚合酶链反应（RT-PCR），评估生黄柏（RPC）、盐炙黄柏、小檗碱（BBR）和小檗红碱（BBRR）对人胚肾293（HEK-293）细胞中肾脏转运蛋白有机阴离子转运体1（OAT1）、有机阴离子转运体3（OAT3）、有机阳离子转运体2（OCT2）、多药及毒素外排蛋白1（MATE1）、多药及毒素外排蛋白2K（MATE2K）、P-糖蛋白（P-gp）和多药耐药相关蛋白2（MRP2）转运能力及表达的影响。
分析表明，BBR和BBRR对OCT2、P-gp、MRP2具有较强的亲和力。与RPC相比，SPC可增加OCT2的摄取能力和表达，同时降低P-gp和MRP2的外排能力及表达。同时，与BBR相比，BBRR对OCT2、P-gp和MRP2表现出相似的作用。因此，SPC增强肾脏靶向作用可归因于BBR部分转化为BBRR对肾脏转运体OCT2、P-gp和MRP2转运能力的差异影响。
本研究考察了肾脏转运蛋白与药物之间的相互作用，旨在阐明SPC增强肾脏靶向作用的机制。本研究结果为探索中药炮制对其他中药归经的影响提供了新的思路和方法。
