Several naturally occuring monoflavonoids, isolated from Scutellaria baicalensis Georgi using silica gel and LH-20 chromatography, inhibited [³H] flunitrazepam binding to the central benzodiazepine receptors (BDZ-Rs) with high to moderately low binding affinity. The most potent one is 5,7,2’-trihydroxy-6,8-dimethoxyflavone (K36) with a K_i of 7.7 nM and the weakest one is baicalin with a K_i of 77.1 μM. _{i A}...[ Read more ]

Several naturally occuring monoflavonoids, isolated from Scutellaria baicalensis Georgi using silica gel and LH-20 chromatography, inhibited [³H] flunitrazepam binding to the central benzodiazepine receptors (BDZ-Rs) with high to moderately low binding affinity. The most potent one is 5,7,2’-trihydroxy-6,8-dimethoxyflavone (K36) with a K_i of 7.7 nM and the weakest one is baicalin with a K_i of 77.1 μM.

The functional properties of wogonin (K_i=1.06 μM) and K36 were determined by electrophysiological studies, employing dorsal root ganglion (DRG) neurons and recombinant GABA_A receptor functionally expressed in Xenopus laevis oocytes. Wogonin and K36 brought about an enhancement of the GABA-activated current, which could be reversed by the co-application of BDZ-R antagonist Ro15-1788. Threshold of stimulation is 0.3-1 μM for wogonin and 1-3 nM for K36. Both wogonin and K36 act as partial positive allosteric modulator at the preference BDZ-R.

The pharmacological effects of wogonin and dichloromethane (DCM) extract were examined in mice. For the large-scale preparation of wogonin, it was crystallized directly from the DCM extract instead of using silica gel chromatography. The purity of the crystal (wogonin) was up to 95 %, which was determined by TLC and HPLC. The acute toxicity of wogonin and DCM extract was low with a LD₅₀ of 3.9 g/kg and 5.9 g/kg, respectively. In acute treatment, wogonin (7.5-30 mg/kg), DCM extract (4-16 mg/kg) and diazepam (1 mg/kg) had a significant anxiolytic effect in the elevated plus-maze test for anxiety. In chronic treatment (5 days pre-treatment), the anxiolytic effect of wogonin (15-30 mg/kg), DCM extract (8 mg/kg) and diazepam (1 mg/kg) were significantly reduced. The anxiolytic effect of wogonin (15 mg/kg ) and DCM extract (8 mg/kg ) was abolished by the BDZ-R antagonist Ro15-1788 (1.25 mg/kg). Wogonin (3.75-30 mg/kg), DCM extract (4-16 mg/kg) and diazepam (1 mg/kg) did not exert any significant effect on locomotor activity acutely or chronically. In the hole-board test, wogonin (7.5-30 mg/kg) and diazepam (1 mg/kg) increased the number of head dips and the time spent in head-dipping both acutely and chronically. However, they had no significant effect on the number of rearing. DCM extract (4-16 mg/kg) had no significant effect on the number of head dips, time spent in head-dipping and rearing acutely and chronically. Based on the results of hole-board test, both wogonin and DCM extract did not have the sedative effect. In the horizontal wire test, diazepam (6 mg/kg) but not wogonin (3.75-30 mg/kg) and DCM extract (4-16 mg/kg) displayed myorelaxant actions.

The results showed that wogonin and K36 are naturally occurring partial positive allosteric modulator of the GABA_A receptor acting at the BDZ-R. Wogonin could be crystallized directly from the DCM extract instead of purifying by silica gel chromatography. Wogoin and DCM extract have a low acute lethality and exert an anxiolytic action without evident myorelaxant and sedative effects. The dose of 7.5 mg/kg (wogonin) and 4 mg/kg (DCM extract) can be used in chronic treatment.