In vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models

Neurapas®balance is a combination of special extracts of Hypericum perforatum (St. John's wort), Passiflora incarnata (passion flower) and Valeriana officinialis (valerian); it is used for the treatment of mild depression, mild anxiety and sleep disorders. Since the daily dose of Hypericum in Neurapas® balance is lower than the doses of Hypericum in single extract phytomedicines, we were interested whether a combination of extracts of Hypericum and Passiflora exerts comparable effects to Neurapas® balance. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced swimming test; in both tests Hypericum has previously been shown to exert pharmacological effects. We show here for the first time, that the Passiflora extract significantly enhances the pharmacological potency of Hypericum in both models. The potency of Hypericum to inhibit serotonin uptake depended on the hyperforin content of the test batches. The dose-dependent enhancement of the Hypericum effect by Passiflora (50µg/ml) resulted in an IC50 of 14µg/ml (Hypericum containing 1% hyperforin) and 9.7µg/ml (Hypericum containing 2.1% hyperforin). A similar synergy between Passiflora and Hypericum extracts was observed in the in vivo model. A greater maximal effect (60% reduced immobility) was observed with Hypericum in a fixed (2:1) combination with Passiflora (90mg/kg) than with higher concentrations (180/360mg/kg) of Hypericum alone (maximal 45% reduced immobility). Our data prove that the anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.