The Effects of Ginsenoside Compound K Against Epilepsy by Enhancing the γ-Aminobutyric Acid Signaling Pathway

Abstract

The imbalance between the GABA-mediated inhibition and the glutamate-mediated excitation is the primary pathological mechanism of epilepsy. GABAergic and glutamatergic neurotransmission have become the most important targets for controlling epilepsy. Ginsenoside compound K (GCK) is a main metabolic production of the ginsenoside Rb1, Rb2, and Rc in the intestinal microbiota. Previous studies show that GCK promoted the release of GABA from the hippocampal neurons and enhanced the activity of GABAA receptors. GCK is shown to reduce the expression of NMDAR and to attenuate the function of the NMDA receptors in the brain. The anti-seizure effects of GCK have not been reported so far. Therefore, this study aimed to investigate the effects of GCK on epilepsy and its potential mechanism. The rat model of seizure or status epilepticus (SE) was established with either Pentylenetetrazole or Lithium chloride-pilocarpine. The Racine’s scale was used to evaluate seizure activity. The levels of the amino acid neurotransmitters were detected in the pilocarpine-induced epileptic rats. The expression levels of GABAARα1, NMDAR1, KCC2, and NKCC1 protein in the hippocampus were determined via western blot or immunohistochemistry after SE. We found that GCK had deceased seizure intensity and prolonged the latency of seizures. GCK increased the contents of GABA, while the contents of glutamate remained unchanged. GCK enhanced the expression of GABAARα1 in the brain and exhibited a tendency to decrease the expression of NMDAR1 protein in the hippocampus. The expression of KCC2 protein was elevated by the treatment of GCK after SE, while the expression of NKCC1 protein was reversely down-regulated. These findings suggested that GCK exerted anti-epileptic effects by promoting the hippocampal GABA release and enhancing the GABAAR-mediated inhibitory synaptic transmission.

Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice

“…Actually, in the past, Rb1 has been proved to modulate GABA A receptor by inhibiting muscimol to the high-affinity site of GABA A receptor [38]. Recently, some groups reported that Ginsenoside compound K (GCK), a main metabolic production of the ginsenoside Rb1, can promote hippocampal GABA release and enhance the GABA A receptor-mediated inhibitory synaptic transmission [39, 40]. These findings suggest Rb1 maybe a key player in the GABAergic transmission in the brain.…”

Overexpressed microRNA-494 represses RIPK1 to attenuate hippocampal neuron injury in epilepsy rats by inactivating the NF-κB signaling pathway

“…was administered to reduce peripheral adverse reactions. Rats were continuously observed 2 h following the injection of pilocarpine [21]. Ethology of rats was observed after the injection of pilocarpine and the rats were marked according to Racine grading.…”

Panax ginseng: a candidate herbal medicine for autoimmune disease

“…Modification of P. ginseng may alter its compounds, resulting in better therapeutic effects for various disorders. 20-O-β-D-glucopyranosyl-20(S)-pro-topanaxadiol, also known as CK, is derived from ginsenosides Rb1, Rb2, and Rc [57]. CK-fortified extract has been used to treat AD-induced mouse models [58].…”