Evidence for Effective Inhibitory Actions on Hyperpolarization-Activated Cation Current Caused by Ganoderma Triterpenoids, the Main Active Constitutents of Ganoderma Spores.

Wei-Ting Chang,Yi-Ching Lo,Zi-Han Gao,Sheng-Nan Wu

doi:10.3390/molecules24234256

Abstract

The triterpenoid fraction of Ganoderma (Ganoderma triterpenoids, GTs) has been increasingly demonstrated to provide effective antioxidant, neuroprotective or cardioprotective activities. However, whether GTs is capable of perturbing the transmembrane ionic currents existing in electrically excitable cells is not thoroughly investigated. In this study, an attempt was made to study whether GTs could modify hyperpolarization-activated cation currents (Ih) in pituitary tumor (GH3) cells and in HL-1 atrial cardiomyocytes. In whole-cell current recordings, the addition of GTs produced a dose-dependent reduction in the amplitude of Ih in GH3 cells with an IC50 value of 11.7 µg/mL, in combination with a lengthening in activation time constant of the current. GTs (10 µg/mL) also caused a conceivable shift in the steady-state activation curve of Ih along the voltage axis to a more negative potential by approximately 11 mV. Subsequent addition of neither 8-cyclopentyl-1,3-dipropylxanthine nor 8-(p-sulfophenyl)theophylline, still in the presence of GTs, could attenuate GTs-mediated inhibition of Ih. In current-clamp voltage recordings, GTs diminished the firing frequency of spontaneous action potentials in GH3 cells, and it also decreased the amplitude of sag potential in response to hyperpolarizing current stimuli. In murine HL-1 cardiomyocytes, the GTs addition also suppressed the amplitude of Ih effectively. In DPCPX (1 µM)-treated HL-1 cells, the inhibitory effect of GTs on Ih remained efficacious. Collectively, the inhibition of Ih caused by GTs is independent of its possible binding to adenosine receptors and it might have profound influence in electrical behaviors of different types of electrically excitable cells (e.g., pituitary and heart cells) if similar in vitro or in vivo findings occur.

Highlights

Ganoderma mushrooms (Língzhıin Chinese, or Reishi in Japanese) are a traditional Chinese herbal medicine that has been widely accepted as a nutritional supplement
In an initial stage of whole-cell experiments designed for the recording of Ih, we bathed cells in Ca2+ -free, Tyrode’s solution and, during the measurements, we filled the pipette by using a
The present results demonstrated that the inhibition by Ganoderma triterpenoids (GTs) of Ih in GH3 cells did not decreaseThe current magnitude altered that the kinetics of the current, is able present resultsbut demonstrated the inhibition by GTsthereby of Ih inindicating

Summary

Introduction

Ganoderma mushrooms (Língzhıin Chinese, or Reishi in Japanese) are a traditional Chinese herbal medicine that has been widely accepted as a nutritional supplement. Triterpenoids have molecular weights ranging from 400 to 600 kDa, and their chemical structure is complex and noted to be highly oxidized [9]. The triterpenoid fraction of Ganoderma, consisting of more than 300 lanostane-tetracyclic compounds, has been growingly demonstrated to be effective at exerting an array of biological actions such as that known either to provide effective antioxidant activities for prevention of myocardial injury, or to produce neuroprotective actions [2,3,4,5,6,10,11,12,13,14,15,16,17,18,19,20,21]. Ganoderma triterpenoids (GTs) could suppress inflammatory response by directly scavenging the free radicals or systemically enhancing the antioxidant enzymes, thereby lowering lipid peroxidase in chicken livers or mice [2,3,8,17,20,21,22,23]

Objectives

Methods

Results

Conclusion