Effects of Zhengtian Pills on Migraine Headache in Rats via Transient Receptor Potential Vanilloid 1

Objective To investigate the effects and molecular mechanism of Zhengtian Pills （ZTP） on migraine headache. Methods All rats were randomly divided into control, positive control, migraine model, low- and high-dose ZTP groups, and glyceryl trinitrate was injected to induce migraine headache. The time of ears turning red, frequency of scratching head, climbing the cage, and head-twitching were used to evaluate rat behaviors. After 10 d administration of ZTP, the expression levels of transient receptor potential vanilloid 1 （TRPV1） both in cortex and hippocampus were determined by Western blotting. Results After 2 min of glyceryl trinitrate injection, rats showed headache phenomena that parallels the clinical symptoms of migraine, which peaked in 30 min, and lasted for 60 min. Frequency of head-twitching and numbers of scratching head in glyceryl trinitrate （GTN） group were significantly increased. In contrast, after ZTP （1.08 g/kg, ig） treatment, the numbers of scratching head with fore-limb, hind-limb and the frequency of head-twitching were significantly decreased. Flunarizine （FLU） and low-dose ZTP （0.54 g/kg） also showed a trend to decrease the numbers of scratching head and head-twitching frequency, but no significant difference. Besides, ZTP significantly decreased the up-regulated TRPV1 protein expression level both in cortex and hippocampus. Conclusion The present study shows that ZTP could significantly improve the migraine symptoms of headache in rats and TRPV1 might be one of the important molecular mechanisms. This is the first report about the effect of ZTP on TRPVl protein expression level both in cortex and hippocampus of rats.

Zhengtian Pills accelerated long term potentiation both in Schaffercollateral-CA1 and perforant path-dentate gyrus synapses

Objective: To investigate the effects of Zhengtian Pills(ZTP) on long term potentiation(LTP) both in Schaffer-CA1 in vitro and perforant path-dentate gyrus(PP-DG) synapses in vivo.Methods: Sprague-Dawley rats were randomly divided into five groups: control, positive control, migraine model, low-, and high-dose ZTP groups. Glyceryl trinitrate(10 mg/kg) was injected subcutaneously to make migraine rat model. Flunarizine(0.9 mg/kg) was set as positive control. Extracellular recording technique in vivo was used to record the effects of ZTP on LTP of PP-DG pathway in anesthetized rats; Using extracellular recording technique in vitro, the effects of ZTP on LTP of Schaffer Collateral-CA1 pathway in rat hippocampal slices were investigated.Results: Compared to the control group, ZTP(1.08 g/kg) significantly enhanced population spike amplitude in PP-DG pathway; Glyceryl trinitrate(10 mg/kg) significantly reduced population spike amplitude in PP-DG pathway; Neither ZTP(0.54 g/kg) nor Flunarizine(0.9 mg/kg) had significant effects on LTP in PP-DG pathway. Compared to the model group, ZTP(1.08 g/kg), ZTP(0.54 g/kg), and flunarizine(0.9 mg/kg) significantly enhanced population spike amplitude in PP-DG pathway. Compared to the control group, ZTP(1.08 g/kg) significantly enhanced field excitatory postsynaptic potential(fEPSP) slope in Schaffer Collateral-CA1 pathway; Glyceryl trinitrate(10 mg/kg) significantly reduced f EPSP slope in Schaffer Collateral-CA1 pathway; Neither ZTP(0.54 g/kg) nor flunarizine(0.9 mg/kg) significant effects on LTP in Schaffer Collateral-CA1 pathway, Compared to the model group, ZTP(1.08 g/kg), ZTP(0.54 g/kg), and Flunarizine(0.9 mg/kg) had significantly enhanced fEPSP slope in Schaffer Collateral-CA1 pathway.Conclusion: Combined with the previous study, the results gave a clue that the effects of ZTP on TRPV1 and hippocampal LTP or their interactions could be the important molecular mechanisms of ZTP acting as migraine and headache medication.