Química y farmacología de una planta medicinal argentina: Artemisia copa / Chemistry and pharmacology of an Argentine medicinal plant: Artemisia copa

Artemisia copa Phil. (Asteraceae) crece en el Noroeste de la Argentina y Norte de Chile. Tradicionalmente se usa para dolores reumáticos, disminuir la presión arterial, dolor de estómago, neumonías, resfríos y como sedante. Con el propósito de estudiar la composición química de A. copa se realizó el análisis fitoquímico de los extractos diclorometánico, etanólico y de la infusión. En el extracto diclorometánico de A. copa se identificaron escopoletina, jaceosidina, espinacetina, penduletina, axilarina y tricina. En el extracto etanólico y la infusión, isovitexina, ácido p-cumárico, luteolina y crisoeriol. En el extracto etanólico se identificó además, luteolina-7-metil-éter. Todos los compuestos aislados, excepto luteolina, fueron informados por primera vez para esta especie vegetal. No se detectó la presencia de artemisinina, presente en Artemisia annua L., por cromatografía en capa delgada. Teniendo en cuenta los usos de A. copa en la medicina tradicional, se evaluó su actividad analgésica y antiinflamatoria (sistémica y local), su actividad sobre el sistema nervioso central, y su actividad espasmolítica, en modelos animales. La infusión mostró actividad analgésica. Los extractos diclorometánico y etanólico exhibieron actividad antiinflamatoria local. En los ensayos para determinar la actividad antiinflamatoria in vitro, los flavonoides aislados de A. copa, espinacetina, jaceosidina, axilarina, crisoeriol, penduletina y tricina inhibieron la producción de mediadores relevantes en la respuesta inflamatoria. Jaceosidina resultó el más activo. La infusión de A. copa mostró actividad ansiolítica y anticonvulsivante en los ensayos realizados para evaluar su actividad sobre el sistema nervioso central en animales. La infusión exhibió además, actividad espasmolítica en el ensayo de yeyuno aislado de rata, predominantemente por el bloqueo de canales de calcio. Crisoeriol, luteolina, y espinacetina resultaron activos ejerciendo su acción por este mecanismo.

Artemisia copa aqueous extract as vasorelaxant and hypotensive agent.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia copa Phil. (Asteraceae) is a medicinal plant commonly used in traditional medicine in Argentina. AIM OF THE STUDY: The vasorelaxant and hypotensive activities of the aqueous extract of Artemisia copa have been investigated. MATERIALS AND METHODS: The in vitro effect of the extract and isolated compounds from Artemisia copa was investigated using isolated rat aortic rings. The acute effect caused by the intravenous (i.v.) infusion (0.1-300mg/kg) on blood pressure and heart rate was evaluated in spontaneous hypertensive rats. In addition, a phytochemical analysis of the extract was performed by HPLC. RESULTS: Artemisia copa had a relaxant effect in endothelium-intact aortic rings that had been pre-contracted with 10(-7)M phenylephrine (Emax=96.7±1.3%, EC50=1.1mg/ml), 10(-5)M 5-hydroxytriptamine (Emax=96.7±3.5%, EC50=1.5mg/ml) and 80mM KCl (Emax=97.9± 4.4%, EC50=1.6mg/ml). In denuded aortic rings contracted by phenylephrine, a similar pattern was observed (Emax=92.7±6.5%, EC50=1.8mg/ml). l-NAME, indomethacin, tetraethylammonium and glibenclamide were not able to block the relaxation induced by the extract. Nevertheless, the pre-treatment with Artemisia copa attenuated the CaCl2-induced contraction in a concentration-dependent manner (Emax: 86% of inhibition for 3mg/ml and 52% de-inhibition for 1mg/ml). This pre-treatment also induced a significant attenuation of the norepinephrine-induced contraction in a concentration-dependent manner (Emax: 72.7% of inhibition for 3mg/ml and 27% de inhibition for 1mg/ml) in a Ca(2+) free medium. Upon analyzing the composition of the extract, the presence of p-coumaric acid, isovitexin, luteolin and chrysoeriol were found. Luteolin (CE50: 1.5µg/ml), chrysoeriol (CE50: 13.2µg/ml) and p-coumaric acid (CE50: 95.2µg/ml), isolated from the aqueous extract, caused dilatation of thoracic aortic rings pre-contracted with phenylephrine. Artemisia copa administered i.v. also induced a decrease in the mean arterial pressure but did not affect the heart rate in hypertensive rats. CONCLUSIONS: The aqueous extract of Artemisia copa proved to have vasorelaxing and hypotensive effects through the inhibition of Ca(2+) influx via membranous calcium channels and intracellular stores. The presence of luteolin, chrysoeriol and p-coumaric acid found in this plant could be involved in this effect.

Spasmolytic activity of Artemisia copa aqueous extract and isolated compounds.

Artemisia copa Phil. (Compositae) is used in popular medicine as a digestive and for gastric pains. The effects of A. copa aqueous extract and its isolated compounds were evaluated on isolated rat jejunum. The extract inhibited non-competitively the cumulative concentration-response curves induced by acetylcholine and CaCl2. The tonic jejunum contractions induced by 80 mM KCl were inhibited by A. copa. Relaxant effects of A. copa on the tonic contraction induced by 25 mM KCl, [EC50: 0.94 mg mL(-1) (0.64-1.39)], was not inhibited by glibenclamide, TEA, l-NAME or methylene blue. Chrysoeriol, spinacetin and luteolin (30 µg mL(-1)), produced an antagonism on the CaCl2 concentration-response curve, showing an inhibition of the maximum contractions (70.0% ± 5.0%, 49.1% ± 4.5% and 77.0% ± 3.5% of E max, respectively), whereas tricin did not inhibit when the same concentration was used. A. copa exerts spasmolytic activity by blocking calcium channels and three isolated compounds could be, at least partly, responsible for the effect.

Psychopharmacological effects of Artemisia copa aqueous extract in mice.

OBJECTIVE: To evaluate the aqueous extract from aerial parts of Artemisia copa Phil. (Asteraceae) administered orallyfor its psychopharmacological activities in several experimental models. METHODS: The extract was administered p.o. in Swiss albino mice and tested on pentobarbital-induced hypnosis, locomotor activity, exploration in the hole-board, anxiolytic like profile evaluated in the marble-burying test and anticonvulsant activity on convulsions induced by pentylenetetrazol. RESULTS: Artemisia copa at doses up to 1.5 g/kg produced a dose-dependent sleep induction and potentiation of sub-hypnotic and hypnotic doses of pentobarbital. The extract also produced a dose-dependent increase and decrease in the spontaneous motor activity (0.5-1.5 g/kg, respectively), no disruption or a decrease on exploratory (hole-board) behavioral profiles (0.5-1.5 g/kg respectively) and a dose-related anxiolytic-like activity as indicated by increases in the percentage of marbles they left uncovered in the marble-burying test at doses (0.5 g/kg) that do not disrupt the motor activity. In addition, the extract (1.5 g/kg) produced a significant increase in the latency time and a decrease in the duration of seizures and mortality induced by PTZ 75 mg/kg in mice. CONCLUSION: These results suggest that the aqueous extract of Artemisia copa may contain sedative principles with potential anxiolytic and anticonvulsant activities.

Flavonoids from Artemisia copa with anti-inflammatory activity.

Bioactivity-guided fractionation of the dichloromethane and ethanol extracts from the aerial parts of Artemisia copa led to the isolation of the flavonoids spinacetin, jaceosidin, axillarin, penduletin, tricin and chrysoeriol. These compounds were studied for possible inhibitory activity on the generation of inflammatory mediators in a cell line of mouse macrophages (RAW 264.7) stimulated with lipopolysaccharide. Spinacetin and jaceosidin weakly inhibited nitric oxide production whereas all flavonoids reduced prostaglandin E2 levels to different extents. The most active flavonoid was jaceosidin that inhibited cyclooxygenase-2 activity in a concentration-dependent manner with an IC50 value of 2.8 microM. In addition, the other flavonoids partially inhibited synovial phospholipase A2 activity. These mechanisms may provide a basis for explaining the anti-inflammatory activity of this plant.