Lack of tolerance to the separate or combined hypnotic actions of different partitions of <i>Melissa officinalis</i> (total, ethyl acetate, and aqueous) and methanolic partition of <i>Albizia julibrissin</i>

Abstract Objective The present study investigates the hypnotic action of the methanolic partition of Albizia julibrissin (MPAJ) and various partitions (total, ethyl acetate, and aqueous) of Melissa officinalis (MO) in mice. Methods Pentobarbital‐induced sleep (PIS) time prolongation was used to assess the hypnotic action of test compounds. For the tolerance study, MO and MPAJ were given alone or in combination for 7 days, and then the locomotor activity of the mice was measured as an index of tolerance. Mortality of the herbal extracts was studied after intraperitoneal (i.p.) and oral administration in mice. Results Separate administration of total extracts of Melissa officinalis and methanolic extract of Albizia julibrissin at 12.5 mg/kg significantly increased the PIS time. In the combination of two plants, there was no additional or synergistic increase in sleepiness when compared to the separate administration of each plant ( p &lt; 0.05). In contrast to diazepam, the locomotor activity of the animals was not significantly altered after 7 days of injection with MPAJ or total extract of MO (TEMO), or their combinations. Conclusion Separate administration of TEMO and MPAJ provides significant hypnotic effects. The combination of two extracts, however, does not result in synergistic or additive hypnotic action. The lack of additive effects could be due to possible interaction by components of the two plants. The increase in mortality rate and undesirable reactions observed after i.p. administration of MPAJ is probably due to the absorption of certain toxic compounds that are not normally absorbed after oral administration.