Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat Hippocampal CA1 Neurons

Abstract

Saikosaponin a (SSa), a main constituent of the Chinese herb Bupleurum chinense DC., has been demonstrated to have antiepileptic activity. Recent studies have shown that SSa could inhibit NMDA receptor current and persistent sodium current. However, the effects of SSa on potassium (K+) currents remain unclear. In this study, we tested the effect of SSa on 4AP-induced epileptiform discharges and K+ currents in CA1 neurons of rat hippocampal slices. We found that SSa significantly inhibited epileptiform discharges frequency and duration in hippocampal CA1 neurons in the 4AP seizure model in a dose-dependent manner with an IC 50 of 0.7 μM. SSa effectively increased the amplitude of I Total and I A, significantly negative-shifted the activation curve, and positive-shifted steady-state curve of I A. However, SSa induced no significant changes in the amplitude and activation curve of I K. In addition, SSa significantly increased the amplitude of 4AP-sensitive K+ current, while there was no significant change in the amplitude of TEA-sensitive K+ current. Together, our data indicate that SSa inhibits epileptiform discharges induced by 4AP in a dose-dependent manner and that SSa exerts selectively enhancing effects on I A. These increases in I A may contribute to the anticonvulsant mechanisms of SSa.

A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications

“… 2012 ) and inactivating K + current (Xie et al. 2013 ). It inhibits the activation of p38 MAPK, NF- κ B signaling pathways to attenuate neuropathic pain (Zhou et al.…”

“… 2012 ; Xie et al. 2013 ; Yoon et al. 2012 , 2013 ), and chronic constriction injury rats (Zhou et al.…”

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins

“…SSa also exerts anti-epileptic activity by inhibiting the current of Nmethyl-D-aspartic acid (NMDA) and persistent sodium (Yu et al, 2012) and suppressing epileptiform discharges frequency and increasing the K + current (Xie et al, 2013). Furthermore, several studies showed that SSa alleviates the chronic constriction injury (CCI)-induced neuropathic pain and eliminates the traumatic brain injury-induced neurological function deficits (Mao et al, 2016) through inhibiting inflammatory factors and reducing P38 MAPK and NF-κB signaling pathway.…”

Review of the use of botanicals for epilepsy in complementary medical systems — Traditional Chinese Medicine

“…One recent study in rat epilepsy models demonstrated that the inhibition of the N-methyl-D-aspartate (NMDA) receptor current and INaP may be the underlying mechanisms of saikosaponin's anticonvulsant properties [21]. Furthermore, the authors also demonstrated that saikosaponin enhances transient inactivating potassium currents in rat hippocampal CA1 neurons [22]. Chaihu longgu muli tang (TW-001) is based on chaihu and mixed with 12 other botanicals [23].…”