Effects of Panax Notoginseng Saponins on Esterases Responsible for Aspirin Hydrolysis In Vitro.

Zongxi Sun,Song Liu,Bo Zhao,Shaonan Hu,Yali Wu,Shouying Du,Pengyue Li

doi:10.3390/ijms19103144

Abstract

Herb–drug interactions strongly challenge the clinical combined application of herbs and drugs. Herbal products consist of complex pharmacological-active ingredients and perturb the activity of drug-metabolizing enzymes. Panax notoginseng saponins (PNS)-based drugs are often combined with aspirin in vascular disease treatment in China. PNS was found to exhibit inhibitory effects on aspirin hydrolysis using Caco-2 cell monolayers. In the present study, a total of 22 components of PNS were separated and identified by UPLC-MS/MS. Using highly selective probe substrate analysis, PNS exerted robust inhibitory potency on human carboxylesterase 2 (hCE2), while had a minor influence on hCE1, butyrylcholinesterase (BChE) and paraoxonase (PON). These effects were also verified through molecular docking analysis. PNS showed a concentration-dependent inhibitory effect on hydrolytic activity of aspirin in HepaRG cells. The protein level of hCE2 in HepaRG cells was suppressed after PNS treatment, while the level of BChE or PON1 in the extracellular matrix were elevated after PNS treatment. Insignificant effect was observed on the mRNA expression of the esterases. These findings are important to understand the underlying efficacy and safety of co-administration of PNS and aspirin in clinical practice.

Highlights

Herbs have been used for primary health care for thousands of years before the advent of modern medicines
We further explored the role of Panax notoginseng saponins (PNS) in the protein expression in HepaRG cells
To elucidate the effect of PNS on the transcription factor contributed to the change of the protein level of esterases, we explored mRNA expression in HepaRG cells with PNS treatment

Summary

Introduction

Herbs have been used for primary health care for thousands of years before the advent of modern medicines. It is estimated that approximately 80% of the population in Asian countries currently uses herbs as complementary or alternative medicine [1]. Patients in these countries with complex diseases use herbs more frequently. Some research reported that herbs perturbed the activities of the metabolizing enzymes and/or transporters [2,3,4]. Liver is the primary drug metabolism site and entails a myriad of chemical reactions. HepaRG cell line, derived from a hepatocellular carcinoma, could express a large panel of liver-specific enzymes [5,6,7]

Methods

Results

Discussion

Conclusion