Effects of Sesamin, the Major Furofuran Lignan of Sesame Oil, on the Amplitude and Gating of Voltage-Gated Na+ and K+ Currents.

Ping-Chung Kuo,Sheng-Nan Wu,Shih-Wei Lee,Zi-Han Kao

doi:10.3390/molecules25133062

Abstract

Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na+ currents (INa), erg-mediated K+ currents (IK(erg)), M-type K+ currents (IK(M)), delayed-rectifier K+ currents (IK(DR)) and hyperpolarization-activated cation currents (Ih) identified from pituitary tumor (GH3) cells. The exposure to SSM or SesA depressed the transient and late components of INa with different potencies. The IC50 value of SSM needed to lessen the peak or sustained INa was calculated to be 7.2 or 0.6 μM, while that of SesA was 9.8 or 2.5 μM, respectively. The dissociation constant of SSM-perturbed inhibition on INa, based on the first-order reaction scheme, was measured to be 0.93 μM, a value very similar to the IC50 for its depressant action on sustained INa. The addition of SSM was also effective at suppressing the amplitude of resurgent INa. The addition of SSM could concentration-dependently inhibit the IK(M) amplitude with an IC50 value of 4.8 μM. SSM at a concentration of 30 μM could suppress the amplitude of IK(erg), while at 10 μM, it mildly decreased the IK(DR) amplitude. However, the addition of neither SSM (10 μM) nor SesA (10 μM) altered the amplitude or kinetics of Ih in response to long-lasting hyperpolarization. Additionally, in this study, a modified Markovian model designed for SCN8A-encoded (or NaV1.6) channels was implemented to evaluate the plausible modifications of SSM on the gating kinetics of NaV channels. The model demonstrated herein was well suited to predict that the SSM-mediated decrease in peak INa, followed by increased current inactivation, which could largely account for its favorable decrease in the probability of the open-blocked over open state of NaV channels. Collectively, our study provides evidence that highlights the notion that SSM or SesA could block multiple ion currents, such as INa and IK(M), and suggests that these actions are potentially important and may participate in the functional activities of various electrically excitable cells in vivo.

Highlights

Sesame seeds and sesame oil have been widely recognized as health foods in Asian countries [1,2].In comparison with other edible oils extracted from diverse seeds, sesame oil is extremely stable, possibly due to the effective antioxidant activities presumably attributed to its abundance of lipid-soluble furofuran lignans, such as sesamin (SSM) and sesamolin (SesA) [3,4,5,6,7]
Cells were bathed in Ca2+ -free Tyrode’s solution containing 10 mM tetraethylammonium chloride (TEA) and the recording pipette was backfilled with a Cs+ -containing solution
The principal findings obtained in the present study are as follows

Summary

Introduction

Sesame seeds and sesame oil have been widely recognized as health foods in Asian countries [1,2].In comparison with other edible oils extracted from diverse seeds, sesame oil is extremely stable, possibly due to the effective antioxidant activities presumably attributed to its abundance of lipid-soluble furofuran lignans, such as sesamin (SSM) and sesamolin (SesA) [3,4,5,6,7]. Emerging research has previously demonstrated that SSM and SesA, the two major furofuran lignans of sesame oil, are able to suppress lipid peroxidation in erythrocytes [8], to inhibit the intestinal absorption of cholesterol and hepatic. Earlier reports have revealed that either probucol or the triterpenoid fraction of Ganoderma, known to possesses the antioxidant activity, could perturb the activity of ionic currents in pituitary lactotrophs [15,16]. Whether these therapeutic lignans (e.g., SSM, SesA) can directly perturb the activity of membrane ion currents is largely uncertain. Molecular studies of epileptogenesis have revealed that specific ion channels play essential roles in both genetic and acquired forms of epilepsy, voltage-gated Na+ (NaV ) channels [17,18,19,20,21]

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