Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: possible involvement of GABAergic transmission.

This experiment was performed to investigate the anxiolytic-like effects of sanjoinine A, one of the major alkaloid compounds in Zizyphi Spinosi Semen (ZSS), by using experimental paradigms of anxiety in comparison with a known anxiolytic, diazepam. Sanjoinine A (2.0 mg/kg) increased the percentage of time spent on the open arms and the number of open arms entries in the elevated plus-maze test, increased the number of head dips in the hole-board test, and increased the percentage of time spent in the center zone and the center zone locomotor distance in the open field box experiment. However, sanjoinine A (0.5, 1.0, 2.0 mg/kg) had no effect on locomotor activity, while diazepam (2.0 mg/kg) significantly reduced locomotor activity. Sanjoinine A (0.5, 1.0, 2.0 mg/kg) did not influence the grip force in the grip strength meter test either. Molecular experiments showed that sanjoinine A (2.0, 5.0 microM) increased chloride influx in cultured cerebellar granule cells. In addition, sanjoinine A (5.0 microM) treatment resulted in over-expression of alpha- and gamma-subunits of GABA(A) receptors and glutamic acid decarboxylase (GAD65/67) in cultured cerebellar granule cells. It is concluded that sanjoinine A may have anxiolytic-like effects in the elevated plus-maze, hole-board test and open field test, and these effects may be mediated by GABAergic transmission.