Relaxant effect of flavonoid naringenin on contractile activity of rat colonic smooth muscle

Abstract

Ethnopharmacological relevanceDisturbed gastrointestinal (GI) motility can be associated with smooth muscle abnormalities and dysfunction. Exploring innovative approaches that can modulate the disturbed colonic motility are of great importance for clinical therapeutics. Naringenin, a flavonoid presented in many traditional Chinese herbal medicines, has been shown to have a relaxant effect on different smooth muscles. The aim of the present study was to investigate the effect of naringenin on regulation of GI motility. Material and methodsMechanical recording was used to investigate the effect of naringenin on isolated rat colonic smooth muscle spontaneous contractions. Whole cell patch clamp, intracellular [Ca2+] concentration ([Ca2+]i) and membrane potential measurements were examined on primary cultures of colonic smooth muscle cells (SMCs). A neostigmine-stimulated rat model was utilized to investigate the effect of naringenin in vivo. ResultsNaringenin induced a concentration-dependent inhibition (1–1000μM) on rat colonic spontaneous contraction, which was reversible after wash out. The external Ca2+ influx induced contraction and [Ca2+]i increase were inhibited by naringenin (100μM). In rat colonic SMCs, naringenin-induced membrane potential hyperpolarization was sensitive to TEA and selective large-conductance calcium-activated K+ (BKCa) channel inhibitor iberiotoxin. Under whole cell patch-clamp condition, naringenin stimulated an iberiotoxin-sensitive BKCa current, which was insensitive to changes in the [Ca2+]i concentration. Furthermore, naringenin significantly suppressed neostigmine-enhanced rat colon transit in vivo. ConclusionOur results for the first time demonstrated the relaxant effect of flavonoid naringenin on colon smooth muscle both in vitro and in vivo. The relaxant effect of naringenin was attributed to direct activation of BKCa channels, which subsequently hyperpolarized the colonic SMCs and decreased Ca2+ influx through VDCC. Naringenin might be of therapeutic value in the treatment of GI motility disorders.