Anti-Epileptic Effect of Ganoderma Lucidum Polysaccharides by Inhibition of Intracellular Calcium Accumulation and Stimulation of Expression of CaMKII α in Epileptic Hippocampal Neurons

Abstract

PurposeTo investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II α expression in a model of epileptic neurons were investigated.MethodPrimary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II α protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope.ResultsThe CaMK II α expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2 + fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes.ConclusionGLP may inhibit calcium overload and promote CaMK II α expression to protect epileptic neurons.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

“…CACNB4 could directly couple electrical activity to gene expression, which was responsible for a type of juvenile myoclonic epilepsy[76]. Recent studies had shown that ganoderma lucidum polysaccharides may inhibit calcium overload and promote CaMK II α expression to protect epileptic neurons[77]. …”

Altered Norbin Expression in Patients with Epilepsy and a Rat Model

“…CaMKII is a multifunctional serine/threonine protein kinase in neurons that is involved in regulating neurotransmission and synaptic plasticity in response to neuronal activity-induced calcium signaling 9 . CaMKII-mediated modulation of neuronal sodium current has effect on neuronal excitability in epilepsy 10 , and its inactivation is associated with many experimental models of epilepsy 11 , 12 . CaKMII activity at synapses is associated with epileptogenesis, as well as other changes in the synapse that are related to glutamate receptor activation 13 .…”

Ganoderma lucidum: A Review with Special Emphasis on the Treatment of Various Cancer

“…Glycans consists of arabinose, mannose, fucose, galactose, xylose, glucuronic acid and also glucose [17]. The other pharmacological properties of polysaccharides were reported such as, hepatoprotective [18], neuroprotective effect [19], anti-amnesic effect [20], anti-epileptic effect [21], anti-obesity effect [22], anti-depressant [23], anti-microbial [24][25][26], anticancer effect [27,28] and ant diabetic [29].…”