8-Oxo-9-Dihydromakomakine Isolated from Aristotelia chilensis Induces Vasodilation in Rat Aorta: Role of the Extracellular Calcium Influx.

Fredi Cifuentes,Cristian Paz,Javier Palacios,Chukwuemeka Nwokocha,Adrián Paredes

doi:10.3390/molecules23113050

Abstract

8-Oxo-9-dihydromakomakine is a tetracyclic indole alkaloid extracted from leaves of the Chilean tree Aristotelia chilensis. The present study investigated the effects of this alkaloid on vascular response in tissues isolated from aortic segments obtained from normotensive rats. Our results showed that 8-oxo-9-dihydromakomakine induced a dose-dependent relaxation of aortic rings pre-contracted with phenylephrine (PE; 10−6 M). The vasorelaxation induced by 8-oxo-9-dihydromakomakine in rat aortic rings is independent of endothelium. The pre-incubation of aortic rings with 8-oxo-9-dehydromakomakine (10−4 M) significantly reduced the contractile response to KCl (p < 0.001) more than PE (p < 0.05). The highest dose of 8-oxo-9-dehydromakomakine (10−4 M) drastically reduced the contraction to KCl (6·10−2 M), but after that, PE (10−6 M) caused contraction (p < 0.05) in the same aortic rings. The addition of 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to tetraethylammonium (a voltage-dependent potassium channels blocker; TEA; 5 × 10−3 M; p < 0.01) and BaCl2 (a non-selective inward rectifier potassium channel blocker; 5 × 10−3 M; p < 0.001) in rat aorta. 8-oxo-9-dihydromakomakine (10−5 M) decreased the contractile response to PE in rat aorta in the presence or absence of ouabain (an inhibitor of Na,K-ATPase; 10−3 M; p < 0.05). These results could indicate that 8-oxo-9-dihydromakomakine partially reduces plasma membrane depolarization-induced contraction. In aortic rings depolarized by PE, 8-oxo-9-dihydromakomakine inhibited the contraction induced by the influx of extracellular Ca2+ in a Ca2+ free solution (p < 0.01). 8-oxo-9-dihydromakomakine reduced the contractile response to agonists of voltage-dependent calcium channels type L (Bay K6844; 10−8 M; p < 0.01), likely decreasing the influx of extracellular Ca2+ through the voltage-dependent calcium channels. This study provides the first qualitative analysis indicating that traditional folk medicine Aristotelia chilensis may be protective in the treatment of cardiovascular pathologies.

Highlights

Maqui (Aristotelia chilensis (Molina) Stuntz, Elaeocarpaceae) is a Chilean native tree sacred to theMaqui (Aristotelia chilensis (Molina)Elaeocarpaceae) is a Chilean native sacred to the Araucanian people
Aristotelia chilensis produce various active components including a high concentration of Aristotelia chilensis various active a high concentration of flavonoids in fruits [1,2].produce
Mexican plants shown that triterpenes and vasodilator effects could explain or have suggest vasodilatory activity bypolyphenolic the fruits of compounds

Summary

Introduction

Maqui (Aristotelia chilensis (Molina) Stuntz, Elaeocarpaceae) is a Chilean native tree sacred to theMaqui (Aristotelia chilensis (Molina)Elaeocarpaceae) is a Chilean native sacred to the Araucanian people. Maqui fruits have aroused special interest due to their beneficial properties for human health, such as antioxidant, cardioprotective, anti-inflammatory, and properties human [1,2,3]. Health,These such as antioxidant, cardioprotective, and enzymatic enzymaticfor activities bioactivities could be useful for anti-inflammatory, the treatment of vascular diseases activities [1,2,3] These bioactivities could be useful for the treatment of vascular diseases such as such as hypertension, myocardial ischemia, and cerebral infarction, which have become worldwide hypertension, ischemia, epidemics in myocardial modern society [4]. Chemical analysis have components reported that including maqui leaves consists of non-iridoid flavonoids in fruits [1,2]. It is known that several pure monoterpene and polyphenolic compounds

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