Kampo Medicine: Evaluation of the Pharmacological Activity of 121 Herbal Drugs on GABAA and 5-HT3A Receptors.

Günter Gisselmann,Katrin M Hoffmann,Robin Herbrechter,Hanns Hatt,Markus Werner,Peter Lepke,Leopoldo Beltrán,Paul M Ziemba

doi:10.3389/fphar.2016.00219

Abstract

Kampo medicine is a form of Japanese phytotherapy originating from traditional Chinese medicine (TCM). During the last several decades, much attention has been paid to the pharmacological effects of these medical plants and their constituents. However, in many cases, a systematic screening of Kampo remedies to determine pharmacologically relevant targets is still lacking. In this study, a broad screening of Kampo remedies was performed to look for pharmacologically relevant 5-HT3A and GABAA receptor ligands. Several of the Kampo remedies are currently used for symptoms such as nausea, emesis, gastrointestinal motility disorders, anxiety, restlessness, or insomnia. Therefore, the pharmacological effects of 121 herbal drugs from Kampo medicine were analyzed as ethanol tinctures on heterologously expressed 5-HT3A and GABAA receptors, due to the involvement of these receptors in such pathophysiological processes. The tinctures of Lindera aggregata (radix) and Leonurus japonicus (herba) were the most effective inhibitory compounds on the 5-HT3A receptor. Further investigation of known ingredients in these compounds led to the identification of leonurine from Leonurus as a new natural 5-HT3A receptor antagonist. Several potentiating herbs (e.g., Magnolia officinalis (cortex), Syzygium aromaticum (flos), and Panax ginseng (radix)) were also identified for the GABAA receptor, which are all traditionally used for their sedative or anxiolytic effects. A variety of tinctures with antagonistic effects Salvia miltiorrhiza (radix) were also detected. Therefore, this study reveals new insights into the pharmacological action of a broad spectrum of herbal drugs from Kampo, allowing for a better understanding of their physiological effects and clinical applications.

Highlights

The 5-HT3A and GABAA receptors are ionotropic receptors within the cys-loop superfamily of ligand-gated ion channels and possess closely related structures
The inhibition observed by the Salvia miltiorrhiza tincture exceeded an inhibition of 80% of the gammaPharmacological Activity of Herbal Drugs aminobutyric acid (GABA)-induced currents
We believe that a broad screening of the ethanol tinctures of herbal remedies via electrophysiological assays is a reliable method to obtain an overview of the pharmacological action of these compounds on clinically relevant receptors

Summary

Introduction

The 5-HT3A and GABAA receptors are ionotropic receptors within the cys-loop superfamily of ligand-gated ion channels and possess closely related structures. Both of these receptors share a pentameric structure, with each subunit consisting of four transmembrane domains (Connolly and Wafford, 2004). GABAA receptor potentiators and agonists are broadly used for restlessness and insomnia (Calcaterra and Barrow, 2014). The allosteric GABAA receptor potentiator diazepam is commonly used for psychiatric disorders, including anxiety and epilepsy (Calcaterra and Barrow, 2014). Specific 5-HT3 receptor antagonists such as ondansetron are mainly used for the treatment of nausea for various conditions, including chemotherapy-induced nausea and vomiting (CINV) and nausea during the postoperative phase (PONV; Cubeddu et al, 1994; Gyermek, 1995)

Objectives

Methods

Results

Discussion

Conclusion