Abstract

Inflammatory bowel disease (IBD) is a serious digestive system disease, for which the clinical therapeutic choices remain limited. Dried fruits of Citrus aurantium L. (CAL) are a traditional medicine used for regulation of the digestive system. The aim of this study was to identify the regulatory effects of CAL on IBD and to clarify the mechanism of the active compounds. In trinitrobenzene sulfonic acid-induced IBD rats, 125 to 500 mg/kg of oral CAL significantly alleviated weight loss and diarrhea, decreased colitis inflammatory cell infiltration, and inhibited pro-inflammatory cytokine production. The mechanisms of characteristic flavonoids in CAL were evaluated involving inflammation and intestine contraction aspects. Naringenin, nobiletin, and hesperetin showed anti-inflammatory effects on lipopolysaccharide-induced RAW cells. The mechanism may be related to the inhibition of the tumor necrosis factor-α (TNF-α)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway to suppress cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Naringenin and nobiletin showed inhibitory effects on isolated jejunum contraction. The mechanism of naringenin is partly related to COX, NOS, inositol triphosphate (IP3), and finally, to decreased jejunum motility. This study demonstrated that CAL, and its flavonoids’ regulatory effects on IBD through anti-inflammation and inhibition of intestine muscle contraction, can provide basic information on developing new drugs or supplements against IBD based on CAL.

Highlights

  • Inflammatory bowel disease (IBD) is a serious digestive system disease, characterized as a chronic and relapsing inflammation of the gastrointestinal tract [1]

  • In this paper, we found that Citrus aurantium L. (CAL) 70% ethanol (EtOH) extract had an amelioratory effect on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD rats

  • To define whether CAL had a positive effect on TNBS-induced rats, a series of indices were measured in the experiment, such as body weight, diarrhea and bloody-stool incidence, colon length, etc

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Summary

Introduction

Inflammatory bowel disease (IBD) is a serious digestive system disease, characterized as a chronic and relapsing inflammation of the gastrointestinal tract [1]. Epidemiological studies showed a large variation in the prevalence of IBD in different regions in the world. Patients with IBD may have symptoms of abdominal cramping, bloody diarrhea, and bloating with a change in stool frequency and form. These symptoms are embarrassing and uncomfortable, and they seriously affect the quality of life. Gut luminal factors, such as food, microbiota, and bile acids, together with their internal interactions might be important for the generation of symptoms in IBD patients. The pathogenesis of IBD is yet to be fully elucidated [8]

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