Effects of Chaihu-Shugan-San on Small Intestinal Interstitial Cells of Cajal in Mice

Abstract

Chaihu-Shugan-San (CSS) has been widely used as an alternative treatment for gastrointestinal (GI) diseases in East Asia. Interstitial cells of Cajal (ICCs) are pacemakers in the GI tract. In the present study, we examined the action of CSS on pacemaker potentials in cultured ICCs from the mouse small intestine in vitro and on GI motility in vivo. We used the electrophysiological methods to measure the pacemaker potentials in ICCs. GI motility was investigated by measuring intestinal transit rates (ITR). CSS inhibited the pacemaker potentials in a dose-dependent manner. The capsazepine did not block the effect of CSS. However, the effects of CSS were blocked by glibenclamide. In addition, N G-nitro-L-arginine methyl ester (L-NAME) also blocked the CSS-induced effects. Pretreatment with SQ-22536 or with KT-5720 did not suppress the effects of CSS; however, pretreatment with ODQ or KT-5823 did. Furthermore, CSS significantly suppressed murine ITR enhancement by neostigmine in vivo. These results suggest that CSS exerts inhibitory effects on the pacemaker potentials of ICCs via nitric oxide (NO)/cGMP and ATP-sensitive K channel dependent and transient receptor potential vanilloid 1 (TRPV1) channel independent pathways. Accordingly, CSS could provide the basis for the development of new treatments for GI motility dysfunction.

Salvia miltiorrhiza induces depolarization of pacemaker potentials in murine small intestinal interstitial cells of Cajal via extracellular Ca2+ and Na+ influx

“…an enhanced chemiluminescence reagent kit (advansta) was used for detection. all other procedures were carried out as previously described (26).…”

Potential antidepressant effects of Traditional Chinese botanical drug formula Chaihu-Shugan-San and its active ingredients

“…Prior research has identified several potential antidepressant mechanisms of CSS. These mechanisms include the regulation of monoaminergic neurotransmitters ( Hwang et al, 2020 ), effects on the HPA axis, anti-inflammatory and neuroplasticity actions ( Li et al, 2019 ), primarily affecting regions such as the hippocampus ( Zhu et al, 2021 ), prefrontal cortex ( Zhang et al, 2021a ) and amygdala ( Ying et al, 2011 ). Extensive research employing various techniques and methods has been conducted to investigate the antidepressant mechanisms of CSS and its active ingredients.…”