Inhibitory Effectiveness of Gomisin A, a Dibenzocyclooctadiene Lignan Isolated from Schizandra chinensis, on the Amplitude and Gating of Voltage-Gated Na+ Current

Wei-Ting Chang,Sheng-Nan Wu

doi:10.3390/ijms21228816

Abstract

Gomisin A (Gom A), a lignan isolated from Schisandra chinensis, has been reported produce numerous biological activities. However, its action on the ionic mechanisms remains largely unanswered. The present experiments were undertaken to investigate the possible perturbations of Gom A or other related compounds on different types of membrane ionic currents in electrically excitable cells (i.e., pituitary GH3 and pancreatic INS-1 cells). The exposure to Gom A led to the differential inhibition of peak and end-pulse components of voltage-gated Na+ current (INa) in GH3 cells with effective IC50 of 6.2 and 0.73 μM, respectively. The steady-state inactivation curve of INa in the presence of Gom A was shifted towards a more hyperpolarized potential. However, neither changes in the overall current-voltage relationship nor those for the gating charge of the current were demonstrated. The application of neither morin (10 μM) nor hesperidin (10 μM) perturbed the strength of INa, while sesamine could suppress it. However, in the continued presence of Gom A, the addition of sesamine failed to suppress INa further. Gom A also effectively suppressed the strength of persistent INa activated by long ramp voltage command, and further application of tefluthrin effectively attenuated Gom A-mediated inhibition of the current. The presence of Gom A mildly inhibited erg-mediated K+ current, while a lack of change in the amplitude of hyperpolarization-activated cation current was observed in its presence. Under cell-attached current recordings, the exposure to Gom A resulted in the decreased firing of spontaneous action currents with a minimal change in AC amplitude. In pancreatic INS-1 cells, the presence of Gom A was also noticed to inhibit peak and end-pulse components of INa differentially with the IC50 of 5.9 and 0.84 μM, respectively. Taken together, the emerging results presented herein provide the evidence that Gom A can differentially inhibit peak and sustained INa in endocrine cells (e.g., GH3 and INS-1 cells).

Highlights

Gomisin A (Gom A, wuweizichu B, wuwèizi chún yı), a dietary dibenzocyclooctadiene lignan compound isolated from the hexane of Schisandra chinensis fruit extract [1,2,3,4,5,6], has been increasingly demonstrated to have anti-inflammatory, anti-oxidative, antihypertensive, neuroprotective, and anti-proliferative properties [7,8,9,10,11]
An earlier study demonstrated the effectiveness of crude S. chinensis extract in decreasing prolactin production in pituitary GH3 cells, suggesting that such an extract could be therapeutically beneficial for patients with hyperprolactinemia and prolactinoma [26]
As the whole-cell current recordings became established, the examined cells were clamped at the level of −80 mV, and an abrupt 50-msec membrane depolarization to −10 mV followed by return to −50 mV was thereafter applied (Figure 1)

Summary

Introduction

Gomisin A (Gom A, wuweizichu B, wuwèizi chún yı), a dietary dibenzocyclooctadiene lignan compound isolated from the hexane of Schisandra chinensis fruit extract [1,2,3,4,5,6], has been increasingly demonstrated to have anti-inflammatory, anti-oxidative, antihypertensive, neuroprotective, and anti-proliferative properties [7,8,9,10,11] This compound was reported to induce protective effects either against hepatic and renal injury induced by CCl4 exposure, or nitropropionic acid-induced striatal toxicity, through differential regulation of the MAPK signal transduction pathway [12,13]. An earlier study demonstrated the effectiveness of crude S. chinensis extract in decreasing prolactin production in pituitary GH3 cells, suggesting that such an extract could be therapeutically beneficial for patients with hyperprolactinemia and prolactinoma [26]

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Conclusion