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

Ethnopharmacological relevance

Disturbed 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 methods

Mechanical 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.

Results

Naringenin induced a concentration-dependent inhibition (1–1000 μM) 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 (100 μM). In rat colonic SMCs, naringenin-induced membrane potential hyperpolarization was sensitive to TEA and selective large-conductance calcium-activated K⁺ (BK_Ca) channel inhibitor iberiotoxin. Under whole cell patch-clamp condition, naringenin stimulated an iberiotoxin-sensitive BK_Ca current, which was insensitive to changes in the Ca²⁺]_i concentration. Furthermore, naringenin significantly suppressed neostigmine-enhanced rat colon transit in vivo.

Conclusion

Our 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 BK_Ca 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.