Abstract
Introduction The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. Methods A search of the literature was performed using PubMed by pairing “interstitial cells of Cajal” with “medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM).” Results From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, 半夏泻心汤, and Yukgunja-tang, 六君子汤) have been shown to modulate ICC functions by both clinical and preclinical data. Conclusion This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents.
Highlights
Functional dyspepsia (FD) is one of the most common gastrointestinal (GI) disorders, affecting 10–30% of the population worldwide [1]
H. pylori eradication, proton pump inhibitors (PPIs), histamine-type-2 receptor antagonists, tricyclic antidepressants (TCAs), and prokinetic drugs are widely used for patients with FD [5]
Known as a hunger hormone, is secreted by enteroendocrine cells and increases food intake. It binds to G protein-coupled receptors and regulates intracellular and extracellular Ca2+ concentrations in ICCs, leading to the generation of pacemaker potential via inositol triphosphate 3 (IP3), Rho kinase, and protein kinase C (PKC)-dependent signaling pathways [24]
Summary
Functional dyspepsia (FD) is one of the most common gastrointestinal (GI) disorders, affecting 10–30% of the population worldwide [1]. E underlying pathophysiology of FD is not yet fully understood, but Helicobacter pylori infection, visceral hypersensitivity, acid disorders, psychosocial factors, and/or abnormal gut motility are considered to be the main contributors to FD [4]. Given these pathological factors, H. pylori eradication, proton pump inhibitors (PPIs), histamine-type-2 receptor antagonists, tricyclic antidepressants (TCAs), and prokinetic drugs are widely used for patients with FD [5]. Herbal medicines are proposed to affect the functions of ICCs, which have complex interactions with surrounding cells and express various receptors for neurotransmitters and circulating hormones [11, 14].
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