RESUMEN
Two novel phenanthrenoids, juncuenin H (1) and dijuncuenin B (2), together with eight known phenanthrenoids, effusol (3), dehydroeffusol (4), juncusol (5), dehydrojuncusol (6), juncuenin B (7), dehydrojuncuenin B (8), juncuenin A (9), and dehydrojuncuenin A (10), were isolated from the underground parts of Juncus setchuenensis. The structures of the compounds were determined by 1D and 2D NMR and mass spectroscopy. The anxiolytic activities of compounds 1, 6, 9, and 10 were evaluated. In order to explore the mechanisms underlying their anxiolytic activities, the levels of serotonin (5-HT), dopamine (DA), and their metabolites in the cerebral cortex and hippocampus of mice treated with compound 1 were determined by quantitative mass spectrometry. The mice treated with compound 1 had significantly lower levels of 5-HT, 3-methoxytyramine (3-MT), 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA), and 3, 4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex than those of the vehicle control-treated mice. The levels of HVA and 5-HIAA in the hippocampus were also significantly lower in the mice treated with compound 1 than in the control group mice. These results suggest that the metabolic changes, reflected in the levels of DA and/or 5-HT, may contribute to the anxiolytic activity of the phenanthrenoids studied herein.
Asunto(s)
Ansiolíticos/farmacología , Corteza Cerebral/efectos de los fármacos , Hipocampo/efectos de los fármacos , Magnoliopsida/química , Fenantrenos/farmacología , Ácido 3,4-Dihidroxifenilacético/análisis , Animales , Ansiolíticos/aislamiento & purificación , Corteza Cerebral/química , China , Dopamina/análogos & derivados , Dopamina/análisis , Hipocampo/química , Ácido Homovanílico/análisis , Masculino , Ratones , Estructura Molecular , Fenantrenos/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Serotonina/análisisRESUMEN
Natural small-molecule phenols (NSMPs) share some bioactivities. The anxiolytic activity of NSMPs is attracting attention in the scientific community. This paper provides data supporting the hypothesis that NSMPs are generally anxiolytic. The anxiolytic activities of seven simple phenols, including phloroglucinol, eugenol, protocatechuic aldehyde, vanillin, thymol, ferulic acid, and caffeic acid, were assayed with the elevated plus maze (EPM) test in mice. The oral doses were 5, 10 and 20 mg/kg, except for phloroglucinol for which the doses were 2.5, 5 and 10 mg/kg. All tested phenols had anxiolytic activity in mice. The phenolic hydroxyl group in 4-hydroxycinnamic acid (4-OH CA) was essential for the anxiolytic activity in the EPM test in mice and rats compared to 4-chlorocinnamic acid (4-Cl CA). The in vivo spike recording of rats' hippocampal neurons also showed significant differences between 4-OH CA and 4-Cl CA. Behavioral and neuronal spike recording results converged to indicate the hippocampal CA1 region might be a part of the anxiolytic pathways of 4-OH CA. Therefore, our study provides further experimental data supporting NSMPs sharing anxiolytic activity, which may have general implications for phytotherapy because small phenols occur extensively in herbal medicines.
Asunto(s)
Ansiolíticos/química , Ansiolíticos/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Fenoles/química , Fenoles/farmacología , Animales , Ansiedad/tratamiento farmacológico , Conducta Animal , Fenómenos Electrofisiológicos/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Estructura Molecular , RatasRESUMEN
Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor, anti-bacterial, and anti-inflammatory activities. Recent literatures have demonstrated that flavonoids have a significant anti-anxiety effect on the central nervous system. In addition, studies showed that flavonoids acted as pro-drugs, which were transformed into smaller phenols through intestinal microflora. The small phenolic metabolites were crucial for the anxiolytic effects of these flavonoids, indicating that natural small-molecule phenols(NSMP) generally have anxiolytic activities. In this paper, the supporting evidences (before June 2016) from SciFinder database have been summarized. Furthermore, NSMPs were classified according to chemical structures; their anxiolytic effects, mechanisms, and the structure-activity relationships were also discussed.