关键词: 高良姜, 大高良姜, 红豆蔻, 胃溃疡寒证, 网络药理学, AKT1, MAP2K1, mTOR

Abstract:

AIM: Through network pharmacology and molecular docking technology, the mechanism of action of three kinds of Alpinia Roxb. Chinese medicinal materials such as Alpiniae Officinarum Rhizoma in the treatment of gastric ulcer with cold syndrome was explored and verified by experiments. METHODS: Through the commonly used technical means of network pharmacology, TCMSP, CNKI and other databases were used to screen the active components in three kinds of Alpinia Roxb. Chinese medicinal materials and related targets for the treatment of gastric ulcer diseases. Venn diagram and protein-protein interaction (PPI) were drawn. Pathway enrichment analysis was performed on key targets. The obtained data of “drug-active ingredient- target- pathway- disease” were imported into Cytoscape 3.10.2 for visualization, and some compounds with higher Degree ranking were selected for molecular docking by AutoDock software. A total of 72 SPF-grade SD rats were divided into nine groups, including a blank control group, a model group, a positive control group (Zingiberis Rhizoma, 10.8 g/kg), high and low dose groups of Alpiniae Officinarum Rhizoma (10.8 and 5.4 g/kg), high and low dose groups of Galangae Rhizoma (9 and 4.5 g/kg), and high and low dose groups of Galangae Fructus (10.8 and 5.4 g/kg). A gastric ulcer with cold syndrome model was induced using cold acetic acid and cold Anemarrhenae Rhizoma. The rats were administered decoctions at different doses by gavage at 1 mL/100 g body weight, twice daily for 4 consecutive days. By calculating the ulcer index and ulcer inhibition rate of rats, the pathological changes of gastric tissue in rats were observed by HE staining, the expression of AKT1, MAP2K1 and mTOR protein in gastric tissue was detected by ELISA, so as to confirm each other with the relevant results of network pharmacology. RESULTS: A total of 45 key components were screened from all the components of three kinds of Alpinia Roxb. Chinese medicinal materials, and 124 targets were intersected with the disease. The PPI network interaction map contained 124 nodes and 923 edges. A total of 138 signal pathways were obtained by KEGG enrichment. The molecular docking scores were less than -7.0 kcal/mol, that is the core components effectively acted on the core targets. The results of verification experiments showed that compared with the model group, the different doses of three kinds of Alpinia Roxb. Chinese medicinal materials groups significantly improved the gastric ulcer with cold syndrome, mucosal edema, congestion and other symptoms caused by the replication of iced Anemarrhenae Rhizoma decoction-glacial acetic acid method, and the ulcer surface and bleeding points were significantly reduced. Compared with the model group, the AKT1 protein expression level was significantly reduced in all drug - treated groups the except low - dose Galangae Fructus group (P<0.05 or P<0.01). The MAP2K1 protein expression level was significantly reduced in all drug - treated groups except the low - dose Alpiniae Officinarum Rhizoma group (P<0.05 or P<0.01). The mTOR protein expression level was significantly reduced in all drug - treated groups except the low - dose Alpiniae Officinarum Rhizoma and Galangae Rhizoma groups (P<0.05 or P<0.01). CONCLUSION: Three kinds of Alpinia Roxb. Chinese medicinal materials may play an anti-inflammatory and regulatory role in cell proliferation through multi-component, multi-target and multi-pathway network regulation and so on to treat gastric ulcer.

Key words: Alpiniae Officinarum Rhizoma, Galangae Rhizoma, Galangae Fructus, gastric ulcer cold syndrome, network pharmacology, AKT1, MAP2K1, mTOR