Bioinformatics and Animal Experiments Reveal Mechanism of Shouhui Tongbian Capsules in Treating Constipation
10.13422/j.cnki.syfjx.20241911
- VernacularTitle:基于生物信息学和实验验证探讨首荟通便胶囊治疗便秘的作用机制
- Author:
Yong LIANG
1
;
Qimeng ZHANG
1
;
Bin GE
1
;
Yang ZHANG
2
;
Yu SHI
2
;
Yue LU
2
;
Hongxi ZHANG
2
Author Information
1. Liaoning University of Traditional Chinese Medicine(TCM),Shenyang 110847,China
2. Tne Third Affiliated Hospital of Liaoning University of TCM, Shenyang 110003,China
- Publication Type:Journal Article
- Keywords:
Shouhui Tongbian capsules;
constipation;
network pharmacology;
molecular docking;
apoptosis;
phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(4):150-157
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules, and constipation-related targets were collected from disease databases. A protein-protein interaction (PPI) network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets, which was followed by gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed, and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets: protein kinase B (Akt1), B-cell lymphoma-2 (Bcl-2), glycogen synthase kinase-3β (GSK-3β), cyclooxygenase-2 (PTGS2), estrogen receptor 1 (ESR1), and epidermal growth factor receptor (EGFR). The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components: auranetin, isosinensetin, naringin, diosmetin, quercetin, apigenin, luteolin, hesperidin, isorhapontigenin, and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules, the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules, the colonic mucosal injury and glandular arrangement were alleviated, and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.