Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Guo X

PROVIDER: S-EPMC8478590 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundYeju Jiangya decoction (CIF) is an herbal formula from traditional Chinese medicine (TCM) for the treatment of hypertension.Materials and methodsBased on the analysis of network pharmacology, combined with in animal experiments, the network pharmacology was used to explore the potential proteins and mechanisms of CIF against hypertension. The bioactive compounds of CIF were screened by using the platform, and the targets of hypertension and CIF were collected. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI) core targets were carried out, and the useful proteins were found by molecular docking technology. Finally, we used N-nitro-L-arginine (L-NNA) induced hypertension model rats to confirm the effect and mechanism of CIF on hypertension.Results14 bioactive compounds of CIF passed the virtual screening criteria, and 178 overlapping targets were identified as core targets of CIF against hypertension. The CIF-related target network with 178 nodes and 344 edges is constructed. The topological results show that quercetin and luteolin are the key components in the network. The key targets NOS3 (nitric oxide synthase 3) and NOS2 (nitric oxide synthase 2) were screened by the protein-protein interaction network. The analysis of target protein pathway enrichment showed that the accumulation pathway is related to the vascular structure of CIF regulation of hypertension. Further verification based on molecular docking results showed that NOS3 had the good binding ability with quercetin and luteolin. On the other hand, NOS3 has an important relationship with the composition of blood vessels. Furthermore, the animal experiment indicated that after the L-NNA-induced hypertension rat model was established, CIF intervention was given by gavage for 3 weeks, and it can decrease serum concentrations of endothelin-1 (ET-1) and thromboxane B2 (TXB2), increase the expression of nitric oxide (NO) and prostacyclin 2 (PGI2), and improve renal, cardiac, and aortic lesions. At the same time, it can reduce blood pressure and shorten vertigo time. Western blot (WB) and immunohistochemistry (IHC) analyses indicated that CIF may downregulate the expression of NOS3, guanylyl cyclase-alpha 1 (GC-α1), guanylyl cyclase-alpha 2 (GC-α2), and protein kinase CGMP-dependent 1 (PRKG1). These results suggest that CIF may play an antihypertensive role by inhibiting the activation of the NOS3/PRKG1 pathway.ConclusionsThe results of this study indicate that CIF has the ability to improve target organs, protect endothelial function, and reduce blood pressure and that CIF might be a potential therapeutic drug for the prevention of hypertension. It provides new insight into hypertension and the potential biological basis and mechanism for CIF clinical research.

Project description:BackgroundCholangiocarcinoma refers to an epithelial cell malignancy with poor prognosis. Yinchenhao decoction (YCHD) showed positive effects on cancers, and associations between YCHD and cholangiocarcinoma remain unclear. This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma.MethodsBy the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods.Results32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions.ConclusionsAs predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effectsthrough multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.