Laxative Effect of Spicatoside A by Cholinergic Regulation of Enteric Nerve in Loperamide-Induced Constipation: ICR Mice Model

Abstract

Researches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of SpiA on chronic constipation, we investigated alterations in the excretion parameters, histological structure, and cholinergic regulation of the enteric nerve in the colons of Institute of Cancer Research (ICR) mice with loperamide (Lop)-induced constipation after exposure to 20 mg/kg of SpiA. Decrease in the number, weight and water contents of stools in the Lop+Vehicle treated group significantly recovered after SpiA treatment, and alterations in the histological structure and transmission electron microscopy (TEM) images were improved in the Lop+SpiA treated group. Similar recovery effects were observed in the ability for mucin secretion and expression of the membrane water channel gene (aquaporin 8, AQP8). Furthermore, significant improvements were observed in the acetylcholinesterase (AChE) activity and acetylcholine receptors’ (AChRs) downstream signaling pathway after treatment of SpiA. The levels of gastrointestinal (GI) hormones including cholecystokinin (CCK) and gastrin were also remarkably enhanced in the Lop+SpiA treated group as compared to the Lop+Vehicle treated group. The expression of receptor tyrosine kinase (C-kit) and protein gene product 9.5 (PGP9.5) in Cajal and neural cells, as well as the phosphorylation of myosin light chain (MLC) in smooth muscle cells, were recovered after SpiA exposure. Taken together, the results of the present study provide the first strong evidence that SpiA improves chronic constipation through muscarinic cholinergic regulation of the enteric nerve in a Lop-induced constipation ICR mice model.

Auricular Vagal Nerve Stimulation Improves Constipation by Enhancing Colon Motility via the Central-Vagal Efferent Pathway in Opioid-Induced Constipated Rats

“…Kovacic et al (54) performed a clinical study using auricular neurostimulation for treating GI disorders in adolescents and reported that its effects were related to vagal efficiency (55). Our previous studies (31,34) reported that loperamide reduced vagal activity via the autonomic-cholinergic function while other studies (56,57) showed inhibitory effects of loperamide on enteric neurons and ICC, similar to the findings in the present study. To further explore whether aVNS was involved in the vagal efferent pathway in loperamide-induced constipated rats, we analyzed the ECG, neural and ICC changes in the ENS.…”

Molecular Characterization of Constipation Disease as Novel Phenotypes in CRISPR-Cas9-Generated Leptin Knockout Mice with Obesity

“…The immunoreactive expression for PGP9.5 was significantly lower in the myenteric and submucosal plexus of BDNF-/- mice with slow gut motility [ 6 ]. The lop-induced constipation institute of cancer research (ICR) and Sprague Dawley (SD) model showed a decrease in two ICC markers (C-kit and SCF), an increase in two enteric-nerve-related factors (transient receptor potential vanilloid 1 (TRPV1) and NOS), and a decrease in the other enteric-nerve-related factors (PGP9.5, Brain-derived neurotrophic factor (BDNF), and GNDT) [ 43 , 44 ]. In a few studies, however, the density and distribution of ICC in patients with slow transit constipation were not significantly different from normal colon [ 45 ].…”

Lactobacillus plantarumKFY02 enhances the relieving effect of gardenoside on montmorillonite induced constipation in mice

“…Another study showed that Cajal bodies (ICC), which have an abnormal number of mesenchymal cells, can cause changes in the cell morphology and network structure, which can slow down colonic peristalsis and induce constipation, which may be the basic pathogenesis of slow transit constipation. 48,49 c-Kit is one of the specic markers of ICC, and is a factor in maintaining ICC proliferation and growth under normal conditions, 50 SCF is a natural ligand of the c-Kit receptor. 51 Studies have found that the concentration of SCF is very important to the cultivation of the ICC.…”