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Abstract

A dichloromethane extract from twigs and leaves of Murraya exotica produced allosteric potentiation of gamma aminobutyric acid (GABA) induced chloride currents in a microelectrode assay in Xenopus laevis oocytes expressing GABA receptors of α₁, β₂, γ_2s subunit composition. The activity was tracked by HPLC-based activity profiling utilizing a zebrafish locomotor activity assay. Osthol (9) was identified as the main active compound. In addition, five other coumarins and four flavonols were identified. Osthol (9) and structurally related coumurrayin (10) were tested in the Xenopus oocyte assay. Compound 9 potentiated GABA_A-induced chloride currents by 487 ± 42%, with an EC₅0 of 46 ± 10 μM, while 10 showed negligible effects on chloride currents. In silico evaluation of physicochemical properties showed that 9 and 10 had properties that are favorable for oral bioavailability and BBB permeability.

Keywords

Murraya exotica Zebrafish larvae HPLC-based activity profiling Osthol

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HPLC-Based Activity Profiling for GABA A Receptor Modulators in Murraya exotica

Abstract

Keywords

References

Supplementary Material