Atractylodes macrocephala Koidzumi modulates human colonic motility via ICCs pacemaker suppression and cAMP/ATP-sensitive K⁺ channel pathways.

Abstract

Atractylodes macrocephala Koidzumi (AMK) is a traditional herbal medicine used for digestive disorders, yet its effects on colonic motility remain poorly understood. This study aimed to investigate the impact of AMK on human colonic contractility and pacemaker activity of interstitial cells of Cajal (ICCs), as well as its in vivo effect on intestinal transit. Human colonic tissues were obtained during non-obstructive colon surgery and used to assess spontaneous smooth muscle contractions and migrating motor complexes (MMCs). Electrophysiological recordings of pacemaker potentials were performed in murine colonic ICCs using whole-cell patch clamp. Pharmacological studies examined the involvement of ATP-sensitive K⁺ channels and cAMP signaling. The intestinal transit rate (ITR) was evaluated in a neostigmine-induced hypermotility mouse model. AMK treatment significantly reduced spontaneous contractions and MMCs in human colonic segments in a dose-dependent manner. In muine colonic ICCs, AMK suppressed pacemaker potentials, with an IC₅₀ of 37.89 µg/mL. This inhibitory effect was reversed by glibenclamide and 8-bromo-cAMP, suggesting involvement of ATP-sensitive K⁺ channels and cAMP-dependent pathways. In vivo, AMK attenuated neostigmine-induced increases in ITR. These findings highlight AMK's potential as a modulator of gastrointestinal motility.