Lotus Leaf Alkaloid Extract Displays Sedative–Hypnotic and Anxiolytic Effects through GABAA Receptor

• Published in: Journal of agricultural and food chemistry 2015-10, Vol.63 (42), p.9277-9285
• Main Authors: Yan, Ming-Zhu, Chang, Qi, Zhong, Yu, Xiao, Bing-Xin, Feng, Li, Cao, Fang-Rui, Pan, Rei-Le, Zhang, Ze-Sheng, Liao, Yong-Hong, Liu, Xin-Min
• Format: Article
• Language: English
• Subjects: Alkaloids - administration & dosage; Animals; Anti-Anxiety Agents - administration & dosage; Anxiety - drug therapy; Anxiety - genetics; Anxiety - metabolism; Anxiety - psychology; Behavior, Animal; Humans; Hypnotics and Sedatives - administration & dosage; Loteae - chemistry; Male; Mice, Inbred ICR; Plant Extracts - administration & dosage; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Sleep Initiation and Maintenance Disorders - drug therapy; Sleep Initiation and Maintenance Disorders - genetics; Sleep Initiation and Maintenance Disorders - metabolism; Sleep Initiation and Maintenance Disorders - psychology
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.5b04141

Lotus leaves have been used traditionally as both food and herbal medicine in Asia. Open-field, sodium pentobarbital-induced sleeping and light/dark box tests were used to evaluate sedative–hypnotic and anxiolytic effects of the total alkaloids (TA) extracted from the herb, and the neurotransmitter levels in the brain were determined by ultrafast liquid chromatography–tandem mass spectrometry. The effects of picrotoxin, flumazenil, and bicuculline on the hypnotic activity of TA, as well as the influence of TA on Cl– influx in cerebellar granule cells, were also investigated. TA showed a sedative–hypnotic effect by increasing the brain level of γ-aminobutyric acid (GABA), and the hypnotic effect could be blocked by picrotoxin and bicuculline, but could not be antagonized by flumazenil. Additionally, TA could increase Cl– influx in cerebellar granule cells. TA at 20 mg/kg induced anxiolytic-like effects and significantly increased the concentrations of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and dopamine (DA). These data demonstrated that TA exerts sedative–hypnotic and anxiolytic effects via binding to the GABAA receptor and activating the monoaminergic system.