A Novel Functional Ingredient Derived From a Mixture of Mulberry (Morus alba L.) Leaves and Butterfly Pea (Clitoria ternatea L.) Flowers Enhances Rapid Eye Movement Sleep, Cognitive Function, and Anxiolytic Behavior via GABAA Receptor-Dependent Mechanism in Rats

Abstract

The neuropharmacological benefits for sleep quality and mental health from the extracts of Morus alba L. leaves (MA) and Clitoria ternatea L. flowers (CT) have been revealed previously. However, due to synergistic interactions of polyherbal ingredients, the positive effects of MA mixed with CT are still controversial. Preliminary outcomes from in vitro assessment exposed that a 3:1 ratio of MA:CT (MACT) yielded the highest antioxidant capacity and gamma-aminobutyric acid (GABA)-promoting activity among seven combination ratios: 0MA:1CT, 1MA:0CT, 1MA:1CT, 1MA:2CT, 1MA:3CT, 2MA:1CT, and 3MA:1CT. Male Wistar rats (n = 6/group) were electroencephalographically and electromyographically monitored to confirm the sedative-hypnotic function of the assigned ingredients over 3 h after oral administration. Cognitive and anxiolytic effects were also evaluated thereafter. Following drug administration, it was found that MACT exhibited positive influences in a dose-dependent manner (125, 250, and 500 mg/kg), and in a significantly better manner than either 500 mg/kg MA or CT alone. Interestingly, a majority of these effects, including sedative-hypnotic parameters, that is, decreasing of latency to rapid eye movements (REMs) sleep and wake duration, increasing of REM sleep duration, number of REM sleep bouts, as well as elevating of cognitive function and anxiolytic parameters was reversed by pretreatment with bicuculline methiodide (2 mg/kg), a GABA<inf>A</inf> receptor antagonist. Overall, the advantages of MACT-based polyherbal drugs, which act preferentially on GABA<inf>A</inf> receptors, may pave the way for further development of MACT as an alternative drug or food supplement for neuropharmacological improvements in GABA<inf>A</inf> receptor-related disorders.