In vitro Effects of Hydroxybenzaldehydes from Gastrodia elata and their Analogues on GABAergic Neurotransmission, and a Structure-Activity Correlation

Abstract

The present study was designed to characterize the modulatory effects of the constituents of Gastrodia elata and their analogues on the GABAergic neurotransmission. 4-Hydroxybenzaldehyde (1) and 4-hydroxy-3-methoxybenzaldehyde (4) inhibited potently the activity of GABA transaminase (IC₅₀ = 4.1 and 5.4 μg/ml, respectively), while the activity of another constituent, 4-hydroxybenzyl alcohol (2), was very weak. Further investigation with 10 analogues revealed a structure-activity correlation, suggesting that the aldehyde group and the hydroxy group at C-4 are necessary for the inhibitory effect on the enzyme activity. Some potent enzyme inhibitors were examined for the effect on the radioligands to the GABA_A receptor complexes of rat cerebral cortices. Among them, the component 4 dose-dependently increased (20 - 30 %) the binding of [³ H]flunitrazepam in the presence of GABA.

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