Artemisia copa aqueous extract as vasorelaxant and hypotensive agent

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Abstract

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 (0.1–300 mg/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=1.1 mg/ml), 10−5 M 5-hydroxytriptamine (Emax=96.7±3.5%, EC50=1.5 mg/ml) and 80 mM KCl (Emax=97.9± 4.4%, EC50=1.6 mg/ml). In denuded aortic rings contracted by phenylephrine, a similar pattern was observed (Emax=92.7±6.5%, EC50=1.8 mg/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 3 mg/ml and 52% de-inhibition for 1 mg/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 3 mg/ml and 27% de inhibition for 1 mg/ml) in a Ca2+ free medium. Upon analyzing the composition of the extract, the presence of p-coumaric acid, isovitexin, luteolin and chrysoeriol were found. Luteolin (CE50: 1.5 μg/ml), chrysoeriol (CE50: 13.2 μg/ml) and p-coumaric acid (CE50: 95.2 μg/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 Ca2+ 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.

Graphical abstract

Three isolated compounds, p-coumaric acid, luteolin and chrysoeriol showed vasorelaxant effect on isolated aortic rings. They could be responsible, at least in part, of the vasorelaxant effect.

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Introduction

Hypertension is a common disorder leading to several chronic diseases, increasing not only the risk for progression of chronic kidney disease but also for cardiovascular morbidity and mortality. Lifestyle changes, physical exercise and intake of healthy diets can decrease blood pressure, enhance antihypertensive drug efficacy and reduce the risk for cardiovascular diseases. Despite the availability of several types of antihypertensive drugs, a successful treatment for hypertension is difficult to achieve. Thus, the development of new pharmacological tools may help improve the clinical management of this pathology (Laurent et al., 2012). Much attention has been paid to the study of medicinal plants, including the screening of natural bioactive compounds with the ability to cure, prevent or delay the progression of cardiovascular diseases (Pratt, 2010). In this field, Latin America offers a great opportunity, mainly due to its wide diversity of plants and unique seasonal crops growing in extensive natural areas. In this sense, scientific reports have pointed out the therapeutic potential of certain plants and foods in this area (Galvez Ranilla et al., 2010).

Argentina is a South American country having a rich floral biodiversity where about 2000 native plants are used in traditional medicine. The aerial parts of Artemisia copa (AC) Phil. (Asteraceae) are used in popular medicine as antitussive, digestive, febrifugue, and for the treatment of lung diseases and hypertension (Ratera and Ratera, 1980). This native plant is commonly known as “copa-copa” and it is a small bush 30–60 cm high which grows in the North West of Argentina and the North of Chile. This plant has a widespread use in the region and it is sold in markets and local herbs stores (Giberti, 1983). Previous pharmacological studies have shown that Artemisia copa possesses anti-inflammatory, antinociceptive (Miño et al., 2004) and antispasmodic activities (Gorzalczany et al., 2012).

Despite the folkloric use, no scientific evaluation of this plant on the cardiovascular system has been carried out to date. Therefore, experiments were undertaken to evaluate the effects of the aqueous extract of Artemisia copa on both in vitro and in vivo assays. Attempts have been made to investigate some of the possible mechanisms underlying the vasorelaxant activity of the extract. Finally, a phytochemical analysis was performed in order to study the activity of compounds isolated from this species.

Section snippets

List of abbreviations

Acetic acid (AcOH), acetylcholine (Ach), analysis of variance (ANOVA), cycloxygenase (COX), effective concentration 50 (EC50), glibenclamide (GLB), High-performance liquid chromatography (HPLC), intraperitoneal administration (i.p.), intravenous administration (i.v.), l- NG-Nitroarginine methyl ester (l-NAME), mean arterial pressure (MAP), nitric oxide (NO), norepinephrine HCl (NE), NO synthase inhibitor (NOS), phenylephrine (Phe), potassium (K+ ), prostacyclin (PGI2) standard error of the mean

Phytochemical studies

In order to analyze the aqueous extract used in this study, HPLC was performed. The extract showed the presence of p-coumaric acid (Rt: 24.011 min), isovitexin (Rt: 32.309 min), luteolin (Rt: 39.201 min) and chrysoeriol (Rt: 40.629 min). Compounds were identified by comparison with external standards. The corresponding fingerprint chromatogram is shown in Fig. 1.

Effects of Artemisia copa on vascular tonus

The addition of cumulative concentrations of Artemisia copa (0.5–3.5 mg/ml) generated a potent relaxation in endothelium-intact aortic

Discussion

The main finding of the present study is that the extract of Artemisia copa was able to relax rat aortic rings and to reduce the blood pressure of anaesthetized SHR, representing the first attempt to describe the pharmacological evidences of vasodilator and antihypertensive effect of this extract.

Although the relaxation–contraction mechanisms that take place in each smooth muscle type share certain features, differences in the signaling pathways prevailing in vessels and the gastrointestinal

Conclusion

The results presented herein demonstrated, for the first time, that the aqueous extract of Artemisia copa possessed vasorelaxant and antihypertensive effects that may be related to the presence of luteolin, chrysoeriol and p-coumaric acid. The inhibition of Ca2+ influx via membranous calcium channels and its release from the intracellular stores could explain its folkloric repute as antihypertensive agent.

Acknowledgments

This work was supported by Grant 20020110200267BA from the University of Buenos Aires.

References (23)

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