Vasoactive Properties of a Cocoa Shell Extract: Mechanism of Action and Effect on Endothelial Dysfunction in Aged Rats.

Pilar Rodríguez-Rodríguez,Ángel L López De Pablo,Sophida Phuthong,Silvia Cañas,David Ramiro-Cortijo,Kendal Ragusky,Silvia M Arribas,Santiago Ruvira,Miguel Rebollo-Hernanz,María A Martín-Cabrejas,María Dolores Morales

doi:10.3390/antiox11020429

Abstract

Cocoa has cardiovascular beneficial effects related to its content of antioxidant phytochemicals. Cocoa manufacturing produces large amounts of waste, but some by-products may be used as ingredients with health-promoting potential. We aimed to investigate the vasoactive actions of an extract from cocoa shell (CSE), a by-product containing theobromine (TH), caffeine (CAF) and protocatechuic acid (PCA) as major phytochemicals. In carotid and iliac arteries from 5-month and 15-month-old rats, we investigated CSE vasoactive properties, mechanism of action, and the capacity of CSE, TH, CAF and PCA to improve age-induced endothelial dysfunction. Vascular function was evaluated using isometric tension recording and superoxide anion production by dihydroethidium (DHE) staining and confocal microscopy. CSE caused endothelium-dependent vasorelaxation, blocked by L-NAME, but not indomethacin, regardless of sex, age, or vessel type. CSE maximal responses and EC50 were significantly lower compared to acetylcholine (ACh). Arterial preincubation with CSE, TH, CAF or PCA, significantly reduced the number of vascular DHE-positive cells. Compared to adult males, iliac arteries from aged males exhibited reduced ACh concentration-dependent vasodilatation but larger CSE responses. In iliac arteries from aged male and female rats, preincubation with 10−4 M CSE and PCA, but not TH or CAF, improved ACh-relaxations. In conclusion, CSE has vasodilatory properties associated with increased nitric oxide bioavailability, related to its antioxidant phytochemicals, being particularly relevant PCA. Therefore, CSE is a potential food ingredient for diseases related to endothelial dysfunction.

Highlights

We demonstrated that cocoa shell (CSE) relaxes vessels with endothelial dysfunction, such as in aging, being able to improve relaxation to other vasodilators
An aqueous extract derived from the cocoa shell has vasodilatory properties in different vessels, age ranges, and both sexes
CSE has a higher potency compared to classical endothelium-dependent vasodilators, relaxing arteries at very low concentrations

Summary

Introduction

Once thought to be a mere mechanical barrier, the endothelium is currently understood to be a key player in cardiovascular regulation through the synthesis of numerous factors, which maintain the balance between contraction and dilatation, proliferation, and death [2,3]. Endothelial dysfunction refers to the disbalance in the bioavailability of these endothelial factors in favor of contractile and proliferative processes, which leads to increased vessel tone and remodeling [4,5]. Endothelial dysfunction is heavily correlated with aging, much like the overall incidence of CVD, with oxidative stress being a well-known major player [6]. Lack of endogenous antioxidants or increased superoxide anion generated in the arterial wall can play a role. Superoxide anion combines with nitric oxide (NO), one of the key vasodilators in vascular homeostasis, reducing its bioavailability and generating peroxynitrite, a highly oxidizing and stable molecule

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