Vasorelaxation by extracts of Casimiroa spp. in rat resistance vessels and pharmacological study of cellular mechanisms
Graphical abstract
Seed and leaf extracts of Casimiroa spp. induce vasorelaxation in rat caudal and aortic tissues; the effects are dependent from M3 receptor and cGMP-dependent NO pathway. The results support the traditional use of Casimiroa decoctions as antihypertensive in the Mexican ethnomedicine.
Introduction
The genus Casimiroa (Rutaceae) includes few species spontaneous in Central America and Mexico; among these are the most common Casimiroa edulis Llave et Lex., Casimiroa pubescens Ramirez, and Casimiroa calderoniae F. Chiang & Medrano. The best known species is Casimiroa edulis, commonly named “Zapote blanco”, an evergreen tree known for its edible fruits and for traditional medicinal uses, now cultivated in many subtropical countries. The fruits (drupes) are rounded, similar to quince, about 10 cm in diameter, with green skin. Each fruit contains 5–7 seeds characterized by bitter taste. The decoction of the leaves or the seeds is traditionally used for treating anxiety, insomnia and hypertension (Lozoya-Legorreta et al., 1978, Magos and Vidrio, 1991, Vidrio and Magos, 1991). Firstly, the hypotensive activity was reported at the end of 19th century (Anonymous, 1897). Subsequently, the activity of the seed extracts was studied in various animal models in vivo; some authors have shown vasodilatation due to imidazole compounds with activity on histamine receptors (Magos et al., 1999). In guinea pig, rat and dog an initial hypotensive response, rapid but transient, has been highlighted through activation of histamine H1 receptor; followed by a delayed vascular effect, always of dilatation, probably through activation of H3 receptor (Magos and Vidrio, 1991, Vidrio and Magos, 1991, Magos et al., 1999). It was also observed that the H1-receptor-induced relaxation is partly endothelium-dependent, because removing the endothelial layer has caused the loss of the efficacy of aqueous extracts obtained from Casimiroa edulis (Baisch et al., 2004). The hypotensive action of Casimiroa edulis extracts has been related to different types of alkaloids such as N,N-dimethylhistamine and casimiroedine (Randolph Major, 1958, Lozoya-Legorreta et al., 1978, Magos et al., 1999); recently, others authors have evidenced new quinolone alkaloids with hypotensive activity (Awaad et al., 2007).
Magos et al. (1995) have studied vascular effects of pretreatment in vitro with an aqueous extract of Casimiroa edulis (1 mg/ml) showing inhibition of vasoconstriction by norepinephrine, 5-hydroxytryptamine and PGF2α, but not by KCl, independently from endothelium presence. These authors also observed vasoconstriction induced by Casimiroa edulis (0.01–1 mg/ml), through activation of α1-adrenergic receptors (Magos et al., 1995).
Overall there are conflicting data in the literature on vascular activities of Casimiroa; therefore, we investigated in vitro the vascular action of Casimiroa spp. extracts, studying the vascular activities of leaf and seed extracts obtained from Casimiroa calderoniae (Cc1–4), Casimiroa edulis (Ce 5–8), and Casimiroa pubescens (Cp 9–12), in precontracted rat caudal and aortic arteries. By using various pharmacological inhibitors we also studied the mechanisms responsible for the vasorelaxation induced by seed extracts of Casimiroa edulis (Ce8) and Casimiroa pubescens (Cp12).
Section snippets
Plant material
Seeds and leaves of all species were collected in the wild and their voucher specimens were deposited at the Herbarium of Facultad de Ciencias UNAM. Casimiroa pubescens was harvested in June 2007 between Vithe and Cardonalito Towns in Ixmiquilpan County, Hidalgo (voucher number FCME-84833). Casimiroa edulis was collected in July 2007 in the surroundings of Comala County, Colima (voucher number FCME-84859), and Casimiroa calderoniae in December 2007 in the arid zone of Oaxaca at the east of
Results
The dried extracts of leaves and seeds from Casimiroa calderoniae (Cc1, Cc2, Cc3 and Cc4), Casimiroa edulis (Ce5, Ce6, Ce7 and Ce8) and Casimiroa pubescens (Cp9, Cp10, Cp11 and Cp12) were obtained in hexane and methanol (Table 1). The HPLC chromatograms for all extracts of Casimiroa C1–C12 were obtained; Fig. 2 shows an example of them relatively to Cc1. All extracts were characterized using heraclenol, isopimpinellin, heraclenin and phellopterin as external standards (Garcia-Argaez et al., 2003
Discussion
The extracts of leaves and seeds from Casimiroa spp. showed vasorelaxation in tissues precontracted by phenylephrine although with difference in quantitative effects; the most active were the hexanic and methanolic seed extracts from Casimiroa edulis, Ce7 and Ce8, and methanolic seed extract from Casimiroa pubescens, Cp12. These experimental observations support the traditional use in Mexican medicine of Casimiroa as hypotensive treatment.
In the literature, authors evidenced in vivo hypotensive
Acknowledgements
The authors are grateful to E. Conte and S. Buttò for performing some experiments while preparing their degree thesis, and Riccardo Pasquale for performing some HPLC analyses.
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