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Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.

ABSTRACT: BACKGROUND:Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms. PURPOSE:The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards gastric emptying and inhibits colonic tone and phasic pressure activity. In addition to the well-recognized manifestations of cannabinoid hyperemesis, cannabinoid mechanisms result in human and animal models of gastrointestinal and colonic dysmotility. Decreased enteric FAAH activity is associated with colonic inertia in slow transit constipation and, conversely, the orphan G protein-coupled receptor, GPR55, is overexpressed in streptozotocin-induced gastroparesis, suggesting it is involved in inhibition of antral motility. Experimental therapies in gastrointestinal motility and functional disorders are focused predominantly on pain relief mediated through cannabinoid 2 receptors or inhibition of DAGL? to normalize colonic transit. In summary, cannabinoid mechanisms and pharmacology are relevant to the current and future practice of clinical gastroenterology.

SUBMITTER: Camilleri M

PROVIDER: S-EPMC6150799 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.

Camilleri M M

Neurogastroenterology and motility 20180510 9

<h4>Background</h4>Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms.<h4>Purpose</h4>The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards ...[more]

PMID: 29745439

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Project description:BackgroundGastrointestinal motility disorder is a common gastrointestinal disease, which seriously affects life quality. Traditional Chinese medicine (TCM) has been widely used as an alternative therapy for gastrointestinal motility disorder. Acacetin is a natural flavonoid compound that has antioxidant and anti-inflammatory, antidepressant, and anticancer properties. However, the efficacy of Acacetin in the treatment of gastrointestinal motility disorders has not been studied. Our aim was to investigate the mechanism of Acacetin-alleviated gastrointestinal motility disorder and its efficacy based on network pharmacology.MethodsWe performed network pharmacology to predict the active components, match Weishu decoction (WSD) targets in gastrointestinal motility disorders, and investigate its potential pharmacological mechanisms. We performed the GO and KEGG enrichment analysis. In vivo, we investigated the effects of Acacetin in the gastrointestinal motility disorder model.ResultsBased on network pharmacological method, the key active ingredient of WSD was identified as Acacetin, and the enrichment signaling pathway was the PI3K-AKT signaling pathway. Acacetin and Mosapride accelerated gastric emptying time, reduced gastric remnant rate, and increased small intestinal propulsion rate. The levels of GAS and MTL were increased after using Acacetin. These results indicated that Acacetin could improve gastrointestinal motility disorders. Among them, high-dose Acacetin showed a better effect. Acacetin could regulate protein and lipid metabolism in mice with gastrointestinal motility disorder. Furthermore, Acacetin could modulate gastrointestinal inflammation and apoptosis. The detection of the PI3K-AKT signaling pathway-related proteins showed that Acacetin improved gastrointestinal motility disorder by inhibiting the activation of the PI3K-AKT signaling pathway.ConclusionThe key ingredient Acacetin in WSD could alleviate gastrointestinal motility disorder by inhibiting the activation of the PI3K-AKT signaling pathway based on network pharmacology analysis. The efficacy and safety of Acacetin treatment provide strong experimental support for the clinical treatment of gastrointestinal motility disorder.

Dataset Information

Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.

Publications

Cannabinoids and gastrointestinal motility: Pharmacology, clinical effects, and potential therapeutics in humans.

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