Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation

Abstract

Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.

Aquaporins as Targets of Dietary Bioactive Phytocompounds

“…Yin et al found that naringenin increased the mRNA and protein expression levels of AQP3 in the colon, both in apical and lateral mucosal epithelial cells. Furthermore, a positive correlation was observed between this increase in the AQP3 level and the increase in fecal water content (Yin et al, 2018 ). As also shown for quercetin, the antioxidant effects elicited by naringenin in HeLa cells have been recently related to its capacity to facilitate hydrogen peroxide elimination through AQPs.…”

“…Naringenin is a natural flavonoid widely found in citrus fruits and tomatoes, that has been reported to act as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective, and anticancer agent (Yin et al, 2018 ). Naringenin relieved the loperamide-induced constipation by targeting AQP3.…”

Lactobacillus plantarumKFY02 enhances the relieving effect of gardenoside on montmorillonite induced constipation in mice

“…48,49 c-Kit is one of the specic markers of ICC, and is a factor in maintaining ICC proliferation and growth under normal conditions, 50 SCF is a natural ligand of the c-Kit receptor. 51 Studies have found that the concentration of SCF is very important to the cultivation of the ICC. Without SCF, the cultivation of ICC cannot survive.…”

Standardized Natural Citrus Extract dietary supplementation influences sows’ microbiota, welfare, and preweaning piglets’ performances in commercial rearing conditions

“…In fact, Mendel et al (2016 , 2017 ) showed that Hesperidin can possess a myocontractive action on porcine intestines in a concentration-dependant matter. Moreover, the naringenin contained in citrus product has been shown to have a laxative effect ( Yin et al, 2018 ). Although SNCE supports the in vitro growth of Lactobacillu s, a genus with demonstrated effects on intestinal transit ( Husebye et al, 2001 ), the sequencing data does not support this hypothesis.…”