Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels.

Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1-30 µmol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (NaV), calcium (CaV), and delayed rectifier potassium (IK) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC50 values in the range of 1.3-13.3 µmol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (IA) and four types of ligand-gated channels (γ-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50-100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels.

[Effects of light intensity on growth and content of active components of Uncaria rhynchophyll].

The aim of this study was to study the effects of different light intensity on the growth,biomass accumulation and distribution,chlorophyll content and effective components of Uncaria rhynchophylla seedlings,and explore the suitable light intensity conditions for artificial cultivation of U. rhynchophylla seedlings. Three-year-old U. rhynchophylla seedlings were used as experimental materials. Four light intensity levels( 100%,70%-75%,30%-35%,5%-10%) were set up with different layers of black shading net. With the decrease of light intensity,the results showed that the plant height,basal diameter and biomass( root,stem,leaf and hook) of U.rhynchophylla seedlings exhibited the trend of " increase-decrease". Under 70%-75% light intensity,the plant height,basal diameter,biomass( root,stem,leaf,hook) of U. rhynchophylla seedlings were significantly higher than those of other treatments( P< 0. 05);under 5%-10% light intensity,the plant height,basal diameter and biomass( root,hook) of U. rhynchophylla seedlings were significantly lower than those of other treatments( P<0. 05). With the decrease of light intensity,the chlorophyll content of U. rhynchophylla seedlings increased gradually: under 100% light intensity,the chlorophyll content of U. rhynchophylla seedlings were the smallest,while under 100% light intensity,its chlorophyll content was the highest. With the decrease of light intensity,the contents of rhynchophylline and isorhynchophylline in different organs of U. rhynchophylla seedlings varied: under 30%-35% light intensity,the contents of rhynchophylline and isorhynchophylline in hooks and rhynchophylline content in stems were the highest; under 5%-10% light intensity,the contents of rhynchophylline and isorhynchophylline in leaves and stems of U. rhynchophylla were the highest. In conclusion,70%-75% light intensity is suitable for seedling growth and biomass accumulation,and 30%-35% light intensity is suitable for the accumulation of effective components in U. rhynchophylla seedlings.