Taggi Valerio, Schäfer Anima M, Seibert Isabell, Meyer Zu Schwabedissen Henriette E
Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Pharmacol Res Perspect. 2025 Jun;13(3):e70111. doi: 10.1002/prp2.70111.
St John's Wort (SJW), commonly used to treat mild depression, is known to pose a risk of drug-herb interactions through hyperforin-mediated activation of the pregnane X receptor (PXR). This induces transcription and expression of PXR target genes, including the efflux transporter P-glycoprotein (Pgp). While the activation of human PXR by the SJW constituent hyperforin is well established, there are contradictory findings on rodent PXR target genes. This study aimed to further investigate SJW effects on Pgp expression in rats. Male Wistar rats were treated for 10 days with the two commercial SJW formulations, Hyperiplant and Rebalance, which differ in their hyperforin content. Quantitative real-time PCR, western blot analysis, and immunohistochemical staining were applied to test for Pgp mRNA expression and protein abundance in the small intestine (jejunum), liver, and brain (cerebrum). Treatment with the hyperforin-rich Hyperiplant increased protein levels in the brain. However, it did not affect mRNA levels. Besides, there was no impact on Pgp protein abundance in the small intestine or the liver. The hyperforin-poor formulation Rebalance did not affect Pgp expression in any of the investigated tissues. Taken together, our results show that there is a modulation of brain Pgp protein abundance in Hyperiplant-treated animals. As such, we conclude that the inducing effect is governed by a so far unknown regulatory mechanism that most likely does not affect transcription of the transporter.
圣约翰草（SJW）常用于治疗轻度抑郁症，已知其通过金丝桃素介导的孕烷X受体（PXR）激活存在药物与草药相互作用的风险。这会诱导PXR靶基因的转录和表达，包括外排转运蛋白P-糖蛋白（Pgp）。虽然圣约翰草成分金丝桃素对人PXR的激活已得到充分证实，但关于啮齿动物PXR靶基因的研究结果却相互矛盾。本研究旨在进一步探究圣约翰草对大鼠Pgp表达的影响。雄性Wistar大鼠用两种市售圣约翰草制剂Hyperiplant和Rebalance处理10天，这两种制剂的金丝桃素含量不同。应用定量实时PCR、蛋白质印迹分析和免疫组织化学染色来检测小肠（空肠）、肝脏和脑（大脑）中Pgp mRNA表达和蛋白质丰度。用富含金丝桃素的Hyperiplant处理可增加脑中的蛋白质水平。然而，它不影响mRNA水平。此外，对小肠或肝脏中的Pgp蛋白质丰度没有影响。金丝桃素含量低的制剂Rebalance对任何被研究组织中的Pgp表达均无影响。综上所述，我们的结果表明，在经Hyperiplant处理的动物中脑Pgp蛋白质丰度存在调节作用。因此，我们得出结论，这种诱导作用受一种迄今未知的调节机制控制，该机制很可能不影响转运蛋白的转录。
