The Key Ingredient Acacetin in Weishu Decoction Alleviates Gastrointestinal Motility Disorder Based on Network Pharmacology Analysis

Background. Gastrointestinal 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. Methods. We 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. Results. Based 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. Conclusion. The 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.

Therapeutic Assessment of Fractions of Hawthorn on Gastrointestinal Motility Disorder by UPLC-MS/MS-based Metabolomics

Background: Hawthorn, a commonly-used traditional Chinese medicine (TCM) for treating dyspepsia，dysmenorrhea and hyperlipidemia, etc., has been proven to improve gastrointestinal motility, avoid food retention. Due to its complex ingredients, the active fractions responsible for the treatment of improving digestion remain largely unknown. To explore the underlying material and interpret its potential mechanism, the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder was studied based on the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics . Materials and Methods: The rat model of gastrointestinal motility disorder was established by subcutaneous injecting with atropine. The modeled rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn for 5 consecutive days. The stomach, small intestine, plasma samples were collected and then subjected to related measurement (gastric emptying rate and small intestine propulsion rate), UPLC-MS/MS metabolic profiling and multivariate/univariate statistical analysis. Results: The results showed that T3 had the best therapeutic effect, and T1, T2 and T4 with no obvious therapeutic effect, demonstrating that the effective components of hawthorn should be compounds of medium polarity. T3 achieved good therapeutic effects due to the gastrointestinal motility promotion activity, and by rectifying the disturbed amino acid metabolism in gastrointestinal motility disorder model. Conclusion: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Jackhammer Esophagus: From Manometric Diagnosis to Clinical Presentation

Background. Jackhammer esophagus is a hypercontractile esophageal disorder recently brought to light with the advent of high resolution manometry (HRM). As little is known about its clinical presentation, the aim of this study was to identify the clinical characteristics associated with this new gastrointestinal motility disorder. Methods. A retrospective study was conducted on patients visiting the CHUM’s Gastro-Intestinal Motility Center from January 2015 to December 2017. The HRM diagnoses were collated in a database along with age and sex of every individual. The latest Chicago classification (version 3.0) was used. Among all the patients subjected to HRM, those diagnosed with Jackhammer esophagus were included in the study. Patient charts were reviewed to collect relevant demographic and clinical data. Key Results. A total of 36 patients with Jackhammer esophagus were included (62 ± 13 years age, 89% females). Their main symptoms were dysphagia (72%), pyrosis (42%), retrosternal chest pain (36%), and epigastralgia (33%). Other manometric findings were hypertonia (22%) and/or inadequate relaxation (19%) of the lower esophageal sphincter. Among the 26 patients who had esogastroduodenoscopy, hiatal hernia was seen in 3 patients. Pathological gastroesophageal reflux was found in 4 of the 10 patients investigated by pH-monitoring. Conclusions and Inferences. Jackhammer esophagus represents 3% of the HRM diagnoses in this study, with a significant female preponderance. In more than two-thirds of cases, the clinical presentation of Jackhammer esophagus is dysphagia.