The Research Of Inhibitory Regulation Of Piperine/deoxyschisandrin On Hippocampal Neuronal Networks

Epilepsy is one of the most common diseases in neurology department. It's caused by many different kinds of perturbances of normal balance of excitation and inhibition within the central nervous system. Given its chronic and recurrent properties, epilepsy damages patients'life qualities and social work abilities and bring heavy burden to the sufferers and the society. Current clinical antiepileptic drugs could control about 70-80% of the patients'symptoms; 20-30% patients develop to be intractable epilepsy sufferers. Moreover, antiepileptic drugs could not prevent formation of foci and disease process, but only alleviate symptoms of seizures at risk of different adverse effects as the consequences of large doses. The call for less negative and more effective antiepileptic drugs is brought forward to the fundamental researches. Chinese medicine is a promising candidate as clinical anticonvulsive drugs for its long history and therapeutic effectiveness of epilepsy. However, the complication of effective components and underlying elusive mechanism of the Chinese medicines hinder their internationalization and standardization. Here we choose the effective components of two traditional Chinese medicines-piperine (PIP) , deoxyschisandrin (DS) and schisandrin B (Sch B)-to investigate their respective modulation and possible mechanisms on primarily cultured hippocampal neurons, using calcium imaging combined with patch clamp technologies. We get the following conclusions:1. Appropriate concentration of PIP, DS or Sch B respectively and effectively inhibit the frequencies of spontaneous and synchronized calcium oscillations in primarily cultured hippocampal neuronal networks. The inhibitory effects are both dose dependent;2. PIP has no effect on voltage-gated sodium, potassium and calcium channels currents, but has neuroprotective effect on glutamate-induced excitotoxicity; DS decreases voltage-gated sodium and calcium channels currents with no effect on voltage-gated potassium channel currents; 3. PIP remarkably decreases the frequencies of spontaneous synaptic and spontaneous excitatory postsynaptic currents. However, PIP can not block KA,NMDA,Na2ATP induced postsynaptic currents; DS effectively inhibits the frequencies of spontaneous inhibitory postsynaptic currents with no effect on spontaneous excitatory postsynaptic currents;4. The mixtures of DS and Sch B with concentrations lower than respective minimal effective dose remarkably inhibite calcium oscillations. The mixtures of DS and Sch B with different ratios have different effects on the changes of frequencies.5. The mixtures of PIP and DS with concentrations lower than respective minimal effective dose slightly increase the frequencies of calcium oscillations; The mixtures of higher concentions of PIP and DS remarkably decrease the frequencies of calcium oscillations. Mixtures with different ratios of PIP and DS have different effect on the changes of calcium oscillation frequencies.