Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver

Li-Rui Sun,Qiu-Shi Guo,Wei Zhou,Min Li

doi:10.1038/s41598-021-99264-2

Li-Rui Sun, Qiu-Shi Guo + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-99264-2

Copy DOI

Abstract

Chinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.

Highlights

Chinese herbal medicine is widely used because it has a good safety profile and few side effects
Herbal medicines can affect drug metabolism by altering the activity of liver enzymes, such as cytochrome P450 (CYP450), and membrane transporters, such as P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2), which may change the pharmacodynamic process of drugs and cause drug concentrations to change in vivo[4,5]
Dioscorea bulbifera L. rhizomes (DB) extract can enhance the cardiotoxicity of the cardiotoxicity of pirarubicin (THP), according to our study

Summary

Introduction

Chinese herbal medicine is widely used because it has a good safety profile and few side effects. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. Herbal medicines can affect drug metabolism by altering the activity of liver enzymes, such as cytochrome P450 (CYP450), and membrane transporters, such as P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2), which may change the pharmacodynamic process of drugs and cause drug concentrations to change in vivo[4,5]. Dioscorea bulbifera L. is a Chinese herbal medicine that is commonly used in the clinic (Fig. 1B) This herb has a wide range of pharmacological activity. We explored liver and heart injury in mice and assessed the accumulation of THP, the localization and expression of P-gp and Mrp[2] to investigate the mechanisms of the HDI between DB and THP

Methods

Results

Conclusion