Hydroalcoholic Extract of Cuscuta Epithymum Enhances Pentobarbitalinduced Sleep: Possible Involvement of GABAergic System.

BACKGROUND: Insomnia is the most common sleep disorder. The present study was undertaken to evaluate the sedative-hypnotic potential of hydroalcoholic extract (HAE) of Cuscuta epithymum and its fractions. METHOD: HAE and its fractions including: water fraction (WF), ethyl acetate fraction (EAF) and n-hexan fraction (NHF) were i.p administered to male mice and 30 min later pentobarbital (30 mg/kg, i.p.) was injected to induce sleep. Then the latent period and continuous sleeping time were recorded. Besides, 30 mins after administration of HAE motor coordination (rota-rod test) were assessed. Additionally, LD50 of HAE was determined and the possible neurotoxicity of the extract was tested on neural PC12 cells. RESULTS: The HAE and NHF decreased the latency of sleep and significantly increased the duration of sleep induced by pentobarbital. These effects of C. epithymum were reversed by flumazenil. HAE did not affect the animals' performance on the rotarod test. The LD50 value for HAE was found to be 4.8 g/kg. HAE and its fractions had no toxicity effect on the viability of PC12-cell line. CONCLUSION: The results of the present study indicate that the HAE and NHF have significant sedativehypnotic effects in mice without major toxic effect and that the benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant.

HPLC-based activity profiling--discovery of sanggenons as GABAA receptor modulators in the traditional Chinese drug Sang bai pi (Morus alba root bark).

EtOAc extracts from two batches of Morus alba root bark (Sang bai pi) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes, which transiently expressed GABA (A) receptors of the subunit composition α1ß2γ(2S). With the aid of HPLC-based activity profiling of the extract from the first batch, activity was traced to a peak subsequently identified as sanggenon G (3). The second batch had a different phytochemical profile, and HPLC-based activity profiling led to the identification of sanggenon C (4) and a stereoisomer of sanggenon D (2) as positive GABA (A) receptor modulators. The structurally related compound kuwanon L (1) was inactive. The sanggenons represent a new scaffold of positive GABA (A) receptor modulators.

GABA(A) receptor modulators from the Chinese herbal drug Junci Medulla--the pith of Juncus effusus.

The gamma-amino butyric acid (GABA) type A (GABA(A)) receptor represents a crucial target for clinical agents in the treatment of anxiety and insomnia. Using the two-microelectrode voltage clamp technique on recombinant α1ß2γ(2S) GABA (A) receptors, effusol (1) and dehydroeffusol (2) were isolated in a bioactivity-guided approach from the pith of Juncus effusus L. Both compounds concentration-dependently enhanced GABA induced chloride currents (I(GABA)) by a maximum 188 ± 20 (1) and 239 ± 18 % (2), independent of the benzodiazepine (BZ) binding site. This activity on the GABA (A) receptor may explain the traditional use of J. effusus as a sedative and anxiolytic agent in Chinese medicine.

Modulation of radioligand binding to the GABA(A)-benzodiazepine receptor complex by a new component from Cyperus rotundus.

Four sesquiterpenes, beta-selinene, isocurcumenol, nootkatone and aristolone and one triterpene, oleanolic acid were isolated from the ethylacetate fraction of the rhizomes of Cyperus rotundus and tested for their ability to modulate gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor function by radioligand binding assays using rat cerebrocortical membranes. Among these compounds, only isocurcumenol, one of the newly identified constituents of this plant, was found to inhibit [3H]Ro15-1788 binding and enhance [3H]flunitrazepam binding in the presence of GABA. These results suggest that isocurcumenol may serve as a benzodiazepine receptor agonist and allosterically modulate GABAergic neurotransmission via enhancement of endogenous receptor ligand binding.