Abstract

Herb-drug interactions are an important safety concern and this study was conducted regarding the interaction between the natural top-selling antidepressant remedy Hypericum perforatum (Hypericaceae) and conventional drugs. This study examined the influence of acute pretreatment with different extracts of Hypericum perforatum from Serbia on pentobarbital-induced sleeping time, impairment of motor coordination caused by diazepam and paracetamol pharmacokinetics in mice. Ethanolic extract, aqueous extract, infusion, tablet and capsule of Hypericum perforatum were used in this experiment. The profile of Hypericum perforatum extracts as well as paracetamol plasma concentration was determined using RP-HPLC analysis. By quantitative HPLC analysis of active principles, it has been proven that Hypericum perforatum ethanolic extract has the largest content of naphtodianthrones: hypericin (57.77 µg/mL) and pseudohypericin (155.38 µg/mL). Pretreatment with ethanolic extract of Hypericum perforatum potentiated the hypnotic effect of pentobarbital and impairment of motor coordination caused by diazepam to the greatest extent and also increased paracetamol plasma concentration in comparison to the control group. These results were in correlation with naphtodianthrone concentrations. The obtained results have shown a considerable influence of Hypericum perforatum on pentobarbital and diazepam pharmacodynamics and paracetamol pharmacokinetics.

Highlights

  • An increasing percentage of the population is using herbal products, and herbal products’ annual retail sales reflect this growing consumer interest

  • Results obtained from the LC-MS analysis show that ethanolic extraction (ETE) gives the highest values for almost every compound extracted from SJW

  • As it was concluded from the previous tests that naphthodianthrone derivative content is important for interaction with pentobarbital and diazepam we decided to investigate the interaction between paracetamol and only ethanolic extract of SJW, which has the greatest concentration of hypericin and pseudohypericin

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Summary

Introduction

An increasing percentage of the population is using herbal products, and herbal products’ annual retail sales reflect this growing consumer interest The reason for this wide usage is simple—people believe that being natural, all herbs are safe [1,2]. If SJW is applied simultaneously with some drugs, its active principles could show pharmacologically significant interactions with these drugs through induction of cytochrome enzymes and P-glycoprotein [1,3,14,15]. Beside these well-known interactions, there are studies showing that hypericin, as one of the main components in SJW, can inhibit uridine. Bearing in mind the widespread use of SJW and the consideration that herb-drug interactions are an important safety concern, the study was conducted in order to examine the interactions between different preparations of SJW from Serbia and pentobarbital, diazepam and paracetamol as examples of drugs that act on the central nervous system

Results and Discussion
Chemicals and Plant Material
Preparation of the Extracts
Animals and Extracts Administration
Extracts Composition Identification by LC-MS
Naphthodianthrones Identification and Quantification by HPLC-DAD-UV
Induced Sleeping Time Test
Statistical Analysis
Conclusions
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