Effect of a cocoa-enriched diet on immune response and anaphylaxis in a food allergy model in Brown Norway rats

doi:10.1016/j.jnutbio.2015.09.022

The Journal of Nutritional Biochemistry

Volume 27, January 2016, Pages 317-326

https://doi.org/10.1016/j.jnutbio.2015.09.022 Get rights and content

Abstract

Previous studies have demonstrated that cocoa intake decreased Th2 immune-related antibodies in rats. In consequence, we aimed to study in depth this cocoa action, particularly assessing its effect on a rat model of food allergy (FA) and also on an anaphylactic response. The involvement of the intestinal immune system was analyzed to allow the action mechanisms to be investigated. The role of cocoa flavonoids in the antiallergic properties of cocoa was also established. Brown Norway rats were fed either a reference diet or diets containing conventional cocoa (CC) or nonfermented cocoa (NFC). FA to ovalbumin (OVA) was induced and, later, an anaphylactic response was provoked. As expected, the synthesis of anti-OVA IgE and other Th2-related antibodies was inhibited by CC diet. In addition, the release of mast cell protease II after anaphylaxis was partially prevented by CC, although other variables were not modified. The CC diet also attenuated the increase of some Th2-related cytokines released from mesenteric lymph node and spleen cells, and modulated the intestinal gene expression of molecules involved in allergic response. These results demonstrated the local and systemic influence of CC diet. The effects of the NFC diet were weaker than those of CC, suggesting that cocoa components other than flavonoids play a role in cocoa's action. In conclusion, by acting on intestinal and systemic immune functions, a cocoa-enriched diet in rats exhibited a protective effect against FA and partially against anaphylaxis, making this a food of high interest to the fields of health and immunonutrition.

Introduction

Cocoa has a relatively high content of antioxidant flavonoids, mainly flavanols such as epicatechin, catechin and procyanidins [1]. Its immunomodulatory effects in healthy rats have been demonstrated by its modification of the composition and functionality of spleen B and T lymphocytes [2], its promotion of T cell maturation [3] and its ability to decrease the intestinal IgM and IgA secretion [4]. Moreover, in ovalbumin-(OVA) immunized rats, the intake of a cocoa-enriched diet decreases serum-specific IgG1, IgG2a, IgG2c and IgM concentrations [5].

Allergy is an immune disease mainly mediated by IgE. After allergen intake and processing, specific T lymphocytes differentiate and expand into T helper (Th) 2 cells characterized by producing cytokines such as IL-4, IL-5, IL-10 and IL-13, which switch B cell antibody production against the allergen to predominantly IgE [6]. IgE coats the surface of mast cells, binding to the high-affinity IgE receptors (FcεRI), producing their sensitization. Later exposure to the same allergen triggers the mast cell releasing of mediators such as histamine, proteases and cytokines, which result in allergic symptoms involving the skin, respiratory and gastrointestinal systems or even the nervous and cardiovascular systems [7]. Several studies suggest the preventive role of flavonoids in allergic reactions. Thus, in a respiratory allergy model in rodent, chrysin, baicalin or quercitin can suppress the airway hyperresponsiveness, decrease the inflammatory cells in the bronchoalveolar lavage fluid and mucus production, as well as decrease the total or specific IgE synthesis [8], [9], [10]. In mice with allergic rhinitis, the administration of KOB03, mainly containing baicalin, improves the rhinitis symptoms and inhibits the mast cell activation, the release of allergic mediators and the production of inflammatory cytokines [11]. In addition, we have previously reported the inhibitory effect of a cocoa-enriched diet on specific IgE and other Th2-related antibodies in intraperitoneally (ip) sensitized allergic brown Norway (BN) rats [12]. In humans, a clinical trial in persistent allergic rhinitis patients demonstrates the ability of apple polyphenols to ameliorate clinical symptoms [13]. Since these effects are mainly reported in respiratory allergy, it is important to establish the influence of flavonoid intake on food allergy (FA), which, with its increasing prevalence, is a major public health problem in developed countries. FA involves the intestinal immune system and the loss of oral tolerance and can lead to an anaphylactic response (AR) [14]. In this regard, the prevention of the development of FA in mice through the intake of apple polyphenol has been described, providing protection against a decrease in body temperature, inhibiting histamine release and decreasing the specific IgE antibody levels [15], [16], [17]. Based on these antecedents, the present study aimed to study in depth the antiallergic properties of cocoa, in particular assessing its effect on a rat model of FA and also its repercussions on an AR. The intestinal immune system was also analyzed to allow the action mechanisms to be investigated. Finally, the role of cocoa flavonoids on the antiallergic actions of cocoa was established.

Section snippets

Diets

Three types of diets were elaborated (Table 1): reference diet with no polyphenols (RF) and two cocoa-enriched diets either including conventional cocoa (CC) or cocoa flavonoids from nonfermented cocoa (NFC), both containing 0.4% of polyphenols. The CC diet was made up from Natural Forastero cocoa containing 40.18 mg/g of polyphenols provided by Idilia Foods S.L. (formerly Nutrexpa S.L., Barcelona, Spain) The NFC diet was elaborated with an ethanol extract of nonfermented and nonroasted cocoa

Body weight, food and water intake and metabolic hormones

At the end of the study, body weight from the FA-RF group was similar to that of the H-RF (Table 2). However, in the FA-CC group but not in the FA-NFC group, the body weight was lower (P<0.05). Food and water intake was monitored throughout the study, and no significant differences among groups were found (Table 2).

The last day of the study, serum ghrelin concentrations showed no significant differences between groups (Table 2). However, GLP-1 and leptin levels were significantly increased by

Discussion

Previous studies concerning the effect of a cocoa diet on the immune system in rats reveal the ability of a cocoa diet to attenuate serum and intestinal immunoglobulin synthesis [2], [3], [4], [5], [23], [24]. In addition, a diet containing 10% of cocoa in a rat allergy model induced by only an ip immunization demonstrates an important inhibition in Th2-specific antibodies [12]. These results prompted us to ascertain both the effect of this diet on an FA model and its repercussions on AR [18].

Conflict of interests

None declared.

Acknowledgements

The authors would like to thank Dr. Antoni Díez-Noguera and Dr. Trinitat Cambras for lending us the activity meters and Maria Pérez-Cano, Malén Massot-Cladera, Filipa Vicente and Sònia Sánchez for their technical assistance.

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^☆: Grants: This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2011-24279).

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Effect of a cocoa-enriched diet on immune response and anaphylaxis in a food allergy model in Brown Norway rats☆

Abstract

Introduction

Section snippets

Diets

Body weight, food and water intake and metabolic hormones

Discussion

Conflict of interests

Acknowledgements

Pharmacol Res

J Nutr Biochem

Respir Med

J Ethnopharmacol

Phytomedicine

J Ethnopharmacol

Pharmacol Res

FEBS Lett

Toxicol Appl Pharmacol

Methods

Int Immunopharmacol

Food Chem

Arch Biochem Biophys

J Allergy Clin Immunol

Immunity

J Allergy Clin Immunol

J Allergy Clin Immunol

Spleen lymphocyte function modulated by a cocoa-enriched diet

Clin Exp Immunol

Cocoa-enriched diet enhances antioxidant enzyme activity and modulates lymphocyte composition in thymus from young rats

J Agric Food Chem

Influence of a cocoa-enriched diet on specific immune response in ovalbumin-sensitized rats

Mol Nutr Food Res

Immunological mechanisms of allergen-specific immunotherapy

Nat Rev Immunol

Chrysin attenuates allergic airway inflammation by modulating the transcription factors T-bet and GATA-3 in mice

Mol Med Rep

Clinical effects of apple polyphenols on persistent allergic rhinitis: a randomized double-blind placebo-controlled parallel arm study

J Investig Allergol Clin Immunol