Natural almond skin reduced oxidative stress and inflammation in an experimental model of inflammatory bowel disease

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Abstract

The aim of the present study was to examine the effects of natural almond skin (NS) powder in mice subjected to experimental colitis. Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). NS powder was administered daily orally (30 mg/kg). Four days after DNBS administration, colon NF-κB and p-JNK activation was increased as well as TNF-α and IL-1β productions. Neutrophil infiltration, by myeloperoxidase (MPO) activity, in the mucosa was associated with up-regulation of ICAM-1 and P-selectin.

Immunohistochemistry for i-NOS, nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed an intense staining in the inflamed colon. Treatment with NS powder significantly reduced the appearance of diarrhea and body weight loss. This was associated with a significant reduction in colonic MPO activity. NS powder also reduced NF-κB and p-JNK activation, the pro-inflammatory cytokines release, the appearance of i-NOS, nitrotyrosine and PARP in the colon and reduced the up-regulation of ICAM-1 and the expression of P-selectin.

The results of this study suggested that administration of NS powder may be beneficial for treatment of inflammatory bowel disease.

Introduction

Inflammatory bowel disease (IBD) encompasses several chronic inflammatory conditions, most significantly ulcerative colitis and Crohn's disease (CD).

IBS remains a complex and inadequately understood disease. Although the etiology of the disease remains unknown, immunological, infective and genetic factors begin to emerge as candidate mechanisms underlying disturbed sensory and motor function in this syndrome.

Several genes have been implicated in the etiology of CD, the most prominent of which are the NOD2/CARD15 located on chromosome 16 [1], [2], the OCTN1 located on chromosome 5 [3], and the DLG5 located on chromosome 10 [4]. The TLR4 gene has recently been implicated in CD but was not associated with the chromosomal region previously linked to CD.

Several possible mechanisms have been proposed for a bacterial etiology in the development of CD: (1) an immune response to a specific pathogen resulting in intestinal infection [5]; (2) alterations in normal bacterial content of the intestinal tract [6]; (3) a defective mucosal barrier and overwhelming exposure to resident bacteria and their antigens and endotoxins [7]; and (4) alterations to the intestinal immune response [5].

Oxidative stress is thought to play a significant role in the pathogenesis of inflammatory bowel disease, including CD. Endogenous antioxidants such as superoxide dismutase (SOD), glutathione, and catalase are normally able to counteract oxidative stress in the intestinal mucosa. However, inflammation increases the demand for these important antioxidants and results in an imbalance between pro-oxidants and antioxidants, with subsequent mucosal damage.

Taken together, the immunological, infective and genetic mechanisms may help better understand symptom generation and develop novel pharmacological drugs for this condition.

A number of studies have demonstrated positive effects of nut consumption in modifying lipid risk factors for coronary heart disease [8], [9], [10]. Although particular attention has been given to the unsaturated fatty acids, it has been recently suggested that the polyphenols play a role in the beneficial effects observed after nut consumption [11], [12], [13]. The polyphenols localized in almond skins include a variety flavonols, flavanones and simple phenolic acids which have a role in reducing risk factors against chronic inflammatory diseases and ageing disorders [14], [15], [16]. The antioxidant and free radical scavenging activity of almond skin polyphenols have also been demonstrated [17].

We have shown that polyphenols from almond skins are bioaccessible in the upper gastrointestinal (GI) tract and therefore potentially available for absorption during digestion [18]. Furthermore, almond skins exhibited antiviral activity and improve the immune surveillance of peripheral blood mononuclear cells (PBMC) towards viral infection, by triggering the Th1 and Th2 subset [19].

Our recent data suggested a neuroprotective effect of almond skins in spinal cord injury, reducing the development of inflammation and tissue injury [20].

The objectives of the present study were to address whether NS powder exerted protection on the development of colonic inflammation induced by dinitrobenzene sulfonic acid (DNBS) in mice.

Section snippets

Reagents

Biotin blocking kit, biotin-conjugated goat anti-rabbit IgG and avidin–biotin peroxidase complex were obtained from Vector Laboratories (Burlingame, CA, USA). All other reagents and compounds used were purchased from Sigma Chemical Company (Sigma, St. Louis, MO).

Animals

Male adult CD1 mice (25–30 g, Harlan Nossan, Milan, Italy) were housed in a controlled environment and provided with standard rodent chow and water. Mice were housed in stainless steel cages in a room kept at 22 ± 1 °C with a 12-h light,

Effects of NS powder treatment on the degree of colitis

No histological alteration was observed in the colon tissue from sham-treated mice (Fig. 1A see macroscopic score 1D; 2A see histological score 2D). Four days after intra-colonic administration of DNBS, the colon appeared flaccid and filled with liquid stool. The macroscopic inspection of cecum, colon and rectum showed presence of mucosal congestion, erosion and hemorrhagic ulcerations (Fig. 1B see macroscopic score 1D). The histopathological features included a transmural necrosis and edema

Discussion

In the present study we have shown that NS powder attenuated DNBS-induced colitis in the rats. What, then, is the mechanism by which almond skin inhibits colon inflammation caused by injection of DNBS?

The intestinal mucosa is vulnerable to oxidative stress from constant exposure to reactive oxygen species (ROS) generated by the lumen contents [30], [31]. Oxidative stress can cause cell damage either directly or through altering signaling pathways. It has been demonstrated that oxidant-mediated

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