RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora coriacea Juss., a medicinal plant in the family Passifloraceae, is widely used to treat anxiety and depression in Mexican folk medicine. However, its chemical profile and biological activity have not been characterized. AIM OF THE STUDY: The aim of the study was to determine the antidepressant activity, anxiolytic effect, and chemical profile of Passiflora coriacea. MATERIALS AND METHODS: An organic fraction (PcEA) from a hydroalcoholic extract of the aerial parts of P. coriacea was obtained, followed by a chemical analysis and separation, yielding six fractions (PcEA, T1, T2, T1.1, T2.1, and T2.2). Male ICR mice were used to determine the antidepressant activity of selected treatments (PcEA, T1, T2, and T1.1) based on a forced swim test (FST). The anxiolytic-like effects of various treatments (PcEA, T1, T2, T2.1, and T2.2) were determined using the elevated plus maze (EPM) test. RESULTS: The organic fraction of P. coriacea decreased anxiety-like behaviors in mice and increased the time of mobility in the FST. After chemical separation, two compounds were isolated from the species with antidepressant activity and anxiolytic-like effects, T1.1 (tricin 7-O-glucoside) and T2.2 (harmane), respectively. CONCLUSIONS: Compounds isolated from P. coriacea exerted anxiolytic and antidepressant effects in mice based on the EPM and FST. The flavonoid tricin-7-O-glucoside and the alkaloid harmane contributed to these biological activities.
RESUMEN
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Asunto(s)
Antiinflamatorios , Inhibidores de Glicósido Hidrolasas , Lactamas , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Lactamas/química , Lactamas/farmacología , Animales , alfa-Glucosidasas/metabolismo , Simulación del Acoplamiento Molecular , Ratones , Relación Estructura-Actividad , Simulación por Computador , Edema/tratamiento farmacológico , Edema/inducido químicamente , Estructura MolecularRESUMEN
Pharmacodynamic interactions between plant isolated compounds are important to understand the mode of action of an herbal extract to formulate or create better standardized extracts, phytomedicines, or phytopharmaceuticals. In this work, we propose binary mixtures using a leader compound to found pharmacodynamic interactions in inhibition of the NF-κB/AP-1 pathway using RAW-Blue™ cells. Eight compounds were isolated from Castilleja tenuiflora, four were new furofuran-type lignans for the species magnolin, eudesmin, sesamin, and kobusin. Magnolin (60.97%) was the most effective lignan inhibiting the NF-κB/AP-1 pathway, followed by eudesmin (56.82%), tenuifloroside (52.91%), sesamin (52.63%), and kobusin (45.45%). Verbascoside, a major compound contained in wild C. tenuiflora showed an inhibitory effect on NF-κB/AP-1. This polyphenol was chosen as a leader compound for binary mixtures. Verbacoside-aucubin and verbascoside-kobusin produced synergism, while verbascoside-tenuifloroside had subadditivity in all concentrations. Verbascoside-kobusin is a promising mixture to use on NF-κB/AP-1 related diseases and anti-inflammatory C. tenuiflora-based phytomedicines.
Asunto(s)
Antiinflamatorios , Glucósidos , Iridoides , Lignanos , FN-kappa B/antagonistas & inhibidores , Orobanchaceae/química , Fenoles , Factor de Transcripción AP-1/antagonistas & inhibidores , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Línea Celular , Glucósidos/química , Glucósidos/farmacología , Iridoides/química , Iridoides/farmacología , Lignanos/química , Lignanos/farmacología , Ratones , FN-kappa B/metabolismo , Fenoles/química , Fenoles/farmacología , Factor de Transcripción AP-1/metabolismoRESUMEN
Stress is an important factor in the etiology of some illnesses such as gastric ulcers and depression. Castilleja tenuiflora Benth. (Orobanchaceae) is used in Mexican traditional medicine for the treatment of gastrointestinal diseases and nervous disorders. Previous studies indicated that organic extracts from C. tenuiflora had gastroprotective effects and antidepressant activity. In this study, we aimed to evaluate the gastroprotective and antidepressant activity of fractions and isolated compounds from the methanolic extract (MECt) of C. tenuiflora in stressed mice. Chromatographic fractionation of MECt produced four fractions (FCt-1, FCt-2, CFt-3, and FCt-4) as well as four bioactive compounds which were identified using TLC, HPLC and NMR analyses. The cold restraint stress (CRS)-induced gastric ulcer model followed by the tail suspension test and the forced swim test were used to evaluate the gastroprotective effect and antidepressant activity of the extract fractions. FCt-2 and FCt-3 at 100 mg/kg had significant gastroprotective and antidepressant effects. All isolated compounds (verbascoside, teniufloroside and mixture geniposide/ musseanoside) displayed gastroprotective effects and antidepressant activity at 1 or 2 mg/kg. The above results allow us to conclude that these polyphenols and iridoids from C. tenuiflora are responsible for the gastroprotective and antidepressant effects.
Asunto(s)
Iridoides/uso terapéutico , Orobanchaceae/química , Extractos Vegetales/uso terapéutico , Animales , Antiulcerosos/química , Antiulcerosos/uso terapéutico , Antidepresivos/química , Antidepresivos/uso terapéutico , Cromatografía Líquida de Alta Presión , Glucósidos/química , Iridoides/química , Masculino , Metanol/química , Ratones , Fenoles/química , Extractos Vegetales/química , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
Castilleja tenuiflora has been used for the treatment of several Central Nervous System (CNS) diseases. Herein we report the antidepressant activity of the methanol extract from the leaves of this medicinal plant. The oral administration of MeOH extract (500 mg/kg) induced a significant (p < 0.05) decrement of the immobility parameter on Forced Swimming Test (FST) and an increment in the latency and duration of the hypnosis, induced by administration of sodium pentobarbital (Pbi, 40 mg/kg, i.p.). Chemical analysis of this antidepressant extract allowed the isolation of (+)-piperitol-4-O-xylopyranosyl-(1â6)-O-glucopyranoside. This new furofuran lignan diglycoside was named tenuifloroside (1) and its complete chemical structure elucidation on the basis of 1D and 2D NMR spectra analysis of the natural compound 1 and its peracetylated derivative 1a is described. This compound was found together with two flavones-apigenin and luteolin 5-methyl ether-a phenylethanoid-verbascoside-and three iridoids-geniposide, caryoptoside and aucubin. All these compounds were purified by successive normal and reverse phase column chromatography. Tenuifloroside, caryoptoside and luteolin 5-methyl ether were isolated from Castilleja genus for the first time. These findings demonstrate that C. tenuiflora methanol extract has beneficial effect on depressive behaviors, and the knowledge of its chemical constitution allows us to propose a new standardized treatment for future investigations of this species in depressive illness.