Abstract
Albiflorin, a traditional Chinese herb, is a main component of Radix paeoniae Alba, which has been used for the treatment of depressive disorders since ancient times. However, the mechanism of the antidepressant effect of albiflorin is poorly understood. Thus, we explored the binding profile of albiflorin at neurotransmitter receptors and transporters. We also characterised the in vivo effect of albiflorin on monoaminergic systems by using microanalysis to determine the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the hypothalamus of freely moving rats administered albiflorin. We found that albiflorin inhibited the uptake of 5-HT and NE and displayed robust binding affinities for the transporters of both neurotransmitters. By contrast, albiflorin (10 μM) showed no significant affinity to a wide array of central nervous system receptors. The results of our in vivo microdialysis studies showed that administration of albiflorin (3.5, 7.0, 14.0 mg/kg) significantly increased extracellular concentrations of 5-HT and NE in the hypothalamus of freely moving rats. Overall, the current study showed that albiflorin is a novel 5-HT and NE reuptake inhibitor with high selectivity.
Highlights
The monoaminergic system is one of the most important targets in the pathophysiology and therapy of depression[6,7]
We found that albiflorin showed a high affinity for the rat SERT and NET (Table 1)
Our results showed that albiflorin was 3-fold more potent than fluoxetine in binding to the rat SERT (Ki values for albiflorin: 5.25 ± 0.17; fluoxetine: 16.32 ± 1.02 nM; Table 1; Fig. 1a)
Summary
The monoaminergic system is one of the most important targets in the pathophysiology and therapy of depression[6,7]. Monoamine reuptake inhibitors work by binding to their respective transporter proteins located presynaptically. This binding interaction induces an increase in the elimination time of the neurotransmitter cycle; the extracellular concentration of neurotransmitters increases in the synaptic cleft. We used a series of competition binding assays and transporter inhibition bioassays to determine the affinities of albiflorin to the rat and cloned human (h) transporters for the monoamines 5-HT, NE and dopamine (SERT, NET and DAT, respectively). To characterise the in vivo effect of albiflorin on monoaminergic systems, we used microdialysis to determine the extracellular levels of 5-HT and NE in the hypothalamus of freely moving rats administered albiflorin
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