Research On The Anti-anxiety Effects And The Mechanisms Of Rhizoma Coptidis Active Substance

Objective:To investigate the anti-anxiety effect of the Rhizoma Coptidis (RC) extractive and monomeric alkaloids of RC in anxiety model mouse and explore the mechanism.Methods:(1) The pharmacodynamic studies of RC active substance on anxiety models:Anti-anxiety effect of RC active substance (the RC extractive and monomeric alkaloids of RC) was evaluated with two behavior experimental including light-dark box test and elevated plus-maze (EPM) in anxiety mices.(2) The effects of RC active substance on central nervous system:The mice spontaneous locomotor activity test was used to investigate the side effect of RC active substance on central nervous system.(3) The mechanisms of anxiety effects of RC active substance:The content of norepinephrine (NE), dopamine (DA) and5-hydroxytryptamine (5-HT) in brain of the mice tested in the EPM model were detected by high performance liquid chromatography-fluorescence detector (HPLC-FLD) to explore the mechanisms of anxiolytic effects of RC active substance preliminarily.Results:(1) The results from the pharmacodynamic studies of RC active substance showed that the RC extract and monomeric alkaloids of RC had anxiolytic effect. The light-dark box test indicated that the group of extract sample2(18.667±5.08) and sample4(17.001±3.319) could obviously increase the number of transitions (P<0.05). The group of RC extract (127.833±8.245), extract sample1(139.831±8.545), sample2(145.332±4.745) and sample4(149.003±6.228) could obviously increase the time spent in light box (P<0.05) compared the control group (106.832±8.256). The number of rearing in light box (11.003±2.356),the number of transitions (18.604±1.856)and the time in light box (220.201±14.012)in berberine group was significantly increased (P<0.05). RCine group also increased the number of rearing in light box (9.402±1.009) and the time in light box (215.001±13.445). The results of EPM showed that the group of extract sample1(38.778±3.045) and sample4(17.001±3.319) significantly increased (P<0.05) the percentage of staying duration in the total period (OT%). The group of extract sample1(42.756±6.144), sample2(39.089±3.531) and sample3(39.824±3.533) significantly increased (P<0.05) the percentage of the times entering the open arms (OE%). Whereas, OT (109.972+7.703), OT%(45.834±3.032) and OE%(45.533±3.756) of the berberine increased significantly (P<0.05), so did OT%(43.243±2.289) of the RCine group.(2) The results from mice spontaneous locomotor activity test displayed that the RC extractive and monomeric alkaloids of RC had no excitant or inhibitory effects on central nervous system in mice.(3) The results of effects on contents of neurotransmitters in the brain of the mice by RC active substance showed that the contents of DA (78.509±2.229) and5-HT (6.261±0.431) in group of extract sample2were significantly decreased (P<0.05), the contents of NE (43.883±1.032) and5-HT (5.250±0.527) in group of sample3were also significantly decreased (P<0.05), and the contents of5-HT (7.003±0.305) in group of sample4were lower too (P<0.05). The concentration of monoamine neurotransmitters of berberine (NE101.933±3.259; DA107.905±2.274;5-HT14.415±1.841) and RCine (NE97.046±2.041;DA112.132±6.495;5-HT14.710±1.236) were significantly decreased (P<0.05), the contents of DA (109.859±2.679)and5-HT (14.490±1.048)were also significantly reductions in epiberberine (P<0.05), so did the contents of DA (104.872±7.979)in group jateorhizine (P<0.05).Conclusion:RC active substance had certain anxiolytic effect. The mechanism may be related to the regulation the content of NE, DA and5-HT in the brain tissues.