Sedative-hypnotic, anxiolytic and possible side effects of Salvia limbata C. A. Mey. Extracts and the effects of phenological stage and altitude on the rosmarinic acid content.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia limbata C. A. Mey. (Persian name: Maryam Goli-e-labeh dar) has been used for treating central nervous disorders such as insomnia, anxiety and depression in Persian traditional medicine. S. limbata is known for its pharmacological activities which could be at least in a part, upon the presence of rosmarinic acid (RA). However, the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extract has not yet been examined. AIM OF THE STUDY: In the current study the sedative-hypnotic effect, anxiolytic activity, possible side effects, and the mechanism of action of S. limbata extracts were evaluated. Besides, the effects of altitude and phenological stage on the RA content of S. limbata were investigated. MATERIALS AND METHODS: Sedative-hypnotic and anxiolytic effects were evaluated through the pentobarbital induced loss of righting reflex test and open field test, respectively. Flumazenil was used to reveal the mechanism of action. Possible side effects were investigated in the passive avoidance and grip strength tests. Besides, the effects of altitude and phenological stage (vegetative, flowering, and seed setting) on the RA content of S. limbata were evaluated using reversed-phase high-performance liquid chromatography (RP-HPLC). RESULTS: Following behavioral tests, sedative-hypnotic and anxiolytic effects were observed. Since the observed effects were reversed by flumazenil and no side effect on the memory and muscle strength was reported, modulation of the α1-containing GABA-A receptors could be proposed as one of the involved mechanisms. According to the RP-HPLC analysis, harvesting S. limbata in the vegetative stage at the altitude of 2500 m led to the highest content of RA (8.67 ± 0.13 mg/g dry matter). Among different extract of the plant samples collected in the vegetative stage at the altitude of 2500 m, the hydroalcoholic extract showed the highest rosmarinic acid content. CONCLUSION: The obtained results help to find the optimum situation to gain the highest content of RA as well as the pharmacological activity that could be economically important for the pharmaceutical industries.

A comparison of artificial intelligence techniques for predicting hyperforin content in Hypericum perforatum L. in different ecological habitats.

Hyperforin, a major bioactive constituent of Hypericum concentration, is impacted by various phenological phases and soil characteristics. We aimed to design a model predicting hyperforin content in Hypericum perforatum based on different ecological and phenological conditions. We employed artificial intelligence modeling techniques including multilayer perceptron (MLP), radial basis function (RBF), and support vector machine (SVM) to examine the factors critical in predicting hyperforin content. We found that the MLP model (R 2 = .9) is the most suitable and precise model compared with RBF (R 2 = .81) and SVM (R 2 = .74) in predicting hyperforin in H. perforatum based on ecological conditions, plant growth, and soil features. Moreover, phenological stages, organic carbon, altitude, and total N are detected in sensitivity analysis as the main factors that have a considerable impact on hyperforin content. We also report that the developed graphical user interface would be adaptable for key stakeholders including producers, manufacturers, analytical laboratory managers, and pharmacognosists.

Prediction of hypericin content in Hypericum perforatum L. in different ecological habitat using artificial neural networks.

BACKGROUND: Hypericum is an important genus in the family Hypericaceae, which includes 484 species. This genus has been grown in temperate regions and used for treating wounds, eczema and burns. The aim of this study was to predict the content of hypericin in Hypericum perforatum in varied ecological and phenological conditions of habitat using artificial neural network techniques [MLP (Multi-Layer Perceptron), RBF (Radial Basis Function) and SVM (Support Vector Machine)]. RESULTS: According to the results, the MLP model (R2 = 0.87) had an advantage over RBF (R2 = 0.8) and SVM (R2 = 0.54) models and it was relatively accurate in predicting hypericin content in H. perforatum based on the ecological conditions of site including soil types, its characteristics and plant phenological stages of habitat. The results of sensitivity analysis revealed that phenological stages, hill aspects, total nitrogen, altitude and organic carbon are the most influential factors that have an integral effect on the content of hypericin. CONCLUSIONS: The designed graphical user interface will help pharmacognosist, manufacturers and producers of medicinal plants and so on to run the MLP model on new data to easily discover the content of hypericin in H. perforatum by entering ecological conditions of site, soil characteristics and plant phenological stages.

An In-Vivo Study on Anticonvulsant, Anxiolytic, and Sedative-Hypnotic Effects of the Polyphenol-Rich Thymus Kotschyanus Extract; Evidence for the Involvement of GABAA Receptors.

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has been so far devoted to T. kotschyanus, and there is a lack of information on the other neurobehavioral effects and side effects of this species. In the current study, the anticonvulsant, anxiolytic, and sedative-hypnotic, effects of Thymus kotschyanus extract on male NMRI mice were evaluated using pentylenetetrazole, maximal electroshock, elevated plus maze, and pentobarbital-induced sleeping tests. Since phenolic compounds and flavonoids have main roles in pharmacological effects of most plant extracts, the phenolic and flavonoid contents of the extract were measured with Folin-Ciocalteu and AlCl3 reagents. Acute toxicity, passive avoidance, and open field tests were carried out to assess the toxicity of the extract. To find out the possible mechanism of action, flumazenil as the specific GABAA receptor antagonist was used. Anticonvulsant and hypnotic effects of the extract were observed at 400 and 600 mg/kg. The extract at the dose of 200 mg/kg revealed significant anxiolytic effects, but it did not show any adverse effects on learning and memory at all the tested doses. Results of this study indicate that Thymus kotschyanus extract has anticonvulsant , anxiolytic, and hypnotic effects, which are likely related to the ability of some phenolic compounds to activate α1-containing GABAA receptors but more experiments still need to be carried out in order to find the exact mechanism, active component, and the toxicity of the Thymus kotschyanus extract.