Abstract
ABSTRACT Hesperidin, a citrus flavonoid, can exert numerous beneficial effects on human health. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal (GI) tract. In the present study, we investigated potential effects of hesperidin on pacemaker potential of ICC in murine small intestine and GI motility. A whole-cell patch-clamp configuration was used to record pacemaker potential in ICC, and GI motility was investigated in vivo by recording gastric emptying (GE) and intestinal transit rate (ITR). Hesperidin depolarized pacemaker potentials of ICC in a dose-dependent manner. Pre-treatment with methoctramine or 4-DAMP did not inhibit hesperidin-induced pacemaker potential depolarization. Neither a 5-HT3 receptor antagonist (Y25130) nor a 5-HT7 receptor antagonist (SB269970) reduced the effect of hesperidin on ICC pacemaker potential, whereas the 5-HT4 receptor antagonist RS39604 was found to inhibit this effect. In the presence of GDP–β–S, hesperidin-induced pacemaker potential depolarization was inhibited. Moreover, in the presence of U73122 and calphostin C, hesperidin did not depolarize pacemaker potentials. Furthermore, hesperidin accelerated GE and ITR in vivo. These results imply that hesperidin depolarized ICC pacemaker potential via 5-HT4 receptors, G protein, and PLC/PKC dependent pathways and that it increased GI motility. Therefore, hesperidin may be a promising novel drug to regulate GI motility.
Highlights
Polyphenols occur in various plants and are important for their defense systems; flavonoids are a group of polyphenols which are common in edible plants that constitute a large part of human diet (Cho et al 2018; Chung et al 2018; Stevens et al 2019)
Spontaneous pacemaker potentials were observed in Interstitial cells of Cajal (ICC)
5-HT receptors are known to be involved in the function of GI motility, we investigated the involvement of 5HT receptors (Gershon and Tack 2007)
Summary
Polyphenols occur in various plants and are important for their defense systems; flavonoids are a group of polyphenols which are common in edible plants that constitute a large part of human diet (Cho et al 2018; Chung et al 2018; Stevens et al 2019). Hesperidin is known to exert various effects on humans including anti-inflammatory activity (Garg et al 2001). GI motility is controlled by numerous different cell types in the GI tract, and among these, ICC plays a key role (Huizinga et al 1995; Sanders 1996; Kim et al 2005). ICC can generate electrical charges (Huizinga et al 1995; Sanders 1996; Kim et al 2005), and when ICC abundance and intercellular connectivity are reduced, GI motility decreases (Der et al 2000; Wei et al 2014). Potential effects of hesperidin on GI motility have not yet been comprehensively investigated; in the current study, we assessed the effects of hesperidin on ICC in vitro and on GI motility in vivo
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