Study on molecular biological mechanism of Chinese herbal medicines for the treatment of gastric precancerous lesions based on data mining and network pharmacology.

Abstract

To explore the molecular biological mechanisms of Chinese herbal medicines for the treatment of gastric precancerous lesions by data mining and network pharmacology. The keywords "gastric precancerous lesions""gastric precancerous disease""gastric mucosal intraepithelial neoplasia""gastric mucosal heterogeneous hyperplasia""gastric precancerous state""chronic gastritis, atrophic""combined Chinese and Western medicine""Chinese medicine therapy""efficacy evaluation" "randomized controlled trial"were searched in China Journal Full-text Database, Wanfang Data, VIP database, PubMed and Embase from 2001 to 2021. The information was extracted from the literature which met the inclusion and exclusion criteria, and the database was constructed to identify the high-frequency herbal medicines. The top six Chinese herbal medicines were analyzed by the network pharmacology methods, including the acquisition of herbs compounds and gastric precancerous lesions targets using Pharmacology Database and Analysis Platform and GeneCards databases, construction of protein-protein interaction network, and screening of core targets, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of core targets through Metascape platform, etc., to elucidate their active components, targets and pathways. A total of 482 compound prescriptions with 603 herbal medicines were included, and the top 6 herbal medicines with higher application frequency were Ume plum (63.35%), Curcuma longa (58.54%), Paeonia lactiflora (54.06%), Salvia miltiorrhiza (49.92%), Rhizoma alba (46.43%), and Astragalus membranaceus (45.44%). The results of the network pharmacological analysis showed that the active ingredients were 4 types from Ume plum, 3 from Curcuma longa, 9 from Paeonia lactiflora, 13 from Salvia miltiorrhiza, 7 from Astragalus alba, and 9 from Astragalus; 77 predicted targets were in Ume plum, 11 in Curcuma longa, 33 in Paeonia lactiflora, 58 in Salvia miltiorrhiza, 65 in Astragalus alba and 89 in Astragalus; and 98 crossover genes were obtained after these targets were compared with the disease genes, among which HSP90AA1, AKT1, TP53, STAT3, MAPK1 and TNF had higher relevance to the treatment of gastric precancerous lesions. The results of the GO enrichment analysis showed that the active ingredients of high frequency Chinese medicine mostly acted through biological processes such as response to inorganic substance, response to hormone, gland development, positive regulation of cell migration, positive regulation of cell motility, etc. The targets include cellular components such as vesicle lumen, secretory granule lumen, cytoplasmic vesicle lumen, transcription regulator complex, and with molecular functions such as kinase binding, protein kinase binding and DNA-binding transcription factor binding. The results of the KEGG pathway enrichment analysis showed that Paeonia lactiflora, Ulmus lucidus, Salvia miltiorrhiza and Astragalus mainly act through the cancer pathway and PI3K-AKT pathway; Curcuma longa and Rhizoma alba mainly act through the cancer pathway and proteoglycans in cancer, and all six herbs were involved in the cancer pathway and five herbs are involved in the PI3K-AKT pathway. In this study, we obtained the top 6 high-frequency Chinese herbal medicines in the treatment of gastric precancerous lesions by data mining method, and revealed that their mechanisms are involved in cell proliferation, differentiation, immunity, inflammation and other processes mainly through cancer pathway, PI3K-AKT signaling pathway, proteoglycans in cancer.