Mechanism of Polygonum capitatum in treatment of Helicobacter Pylori associated gastritis by network pharmacology, microarray data analysis and molecular docking / 中国药理学通报

Aim To explore the mechanism of Polygonum capitatum(PC)in the treatment of Helicobacter Pylori associated gastritis(HAG). Methods The databases were used to identify the target of PC active compounds and HAG-related genes,and the intersection was taken to obtain the potential targets of PC treatment of HAG. The interaction network diagram of “drug-active compound-target-disease” and the protein-protein interaction(PPI)network of potential target protein interaction in HAG treated by PC were constructed by software Cytoscape 3.6.0. The important nodes in the network were screened by several topological indexes,and the GO and KEGG enrichment were analyzed by STRING database to obtain the potential signaling pathway of PC in the treatment of HAG. The binding ability of PC active components with key target proteins was observed by molecular docking method. On this basis,the related targets of PC in the treatment of HAG were verified in vivo and in vitro experiments. Results The PC active compounds and targets were identified through the database,and the “drug-active compound-target-disease” network diagram and the PPI network of potential target proteins were constructed. Combined with several topological indexes,the PPI network of potential target-protein interaction was analyzed,and 52 hub genes were screened. Further bioinformatics analysis and high-throughput sequencing revealed that PC exerted an effect on HAG through the Akt/NF-κB/NLRP3 pathway. Based on this,it was found that PC could reduce IL-18 and IL-1β in HAG GES-1 cells and HAG SD rats,up-regulate Akt and its phosphorylation level and reduce NF-κB expression,inhibit the activation of NLRP3 inflammatory body,so as to improve HAG inflammatory response. Conclusions PC could exert a therapeutic effect on HAG by activating Akt and its phosphorylation level,and inhibiting the expression of NF-κB and NLRP3 inflammasome related factors. This study provides a theoretical basis for explaining the mechanism of PC in the treatment of HAG.

An overview of traditional Chinese medicine therapy for Helicobacter pylori-related gastritis.

BACKGROUND: Helicobacter pylori-associated gastritis (HPAG) is a common digestive system disease that its therapeutic goal is to eradicate Helicobacter pylori. However, due to the widespread use of antibiotics, problems for example, antibiotic resistance, reinfection, and gastrointestinal side effects have emerged. The solution of above problems provides a broad space for traditional Chinese medicine (TCM) to exert its remarkable advantages on the treatment of HPAG. METHODS: Extensive database retrieval using platforms not limited to but including Web of Science, SpringerLink, ScienceDirect, Google Scholar, China National Knowledge Infrastructure, Wanfang, and VIP database was performed using keywords such as "Helicobacter pylori-associated gastritis" or "HPAG" or "Helicobacter pylori" or "H. pylori" or "gastritis" and "traditional Chinese medicine" or "TCM" or "herbs" or "Chinese herbal medicine". In addition, related books, PhD, and master's dissertations were also researched to provide a comprehensive review. RESULTS: This review mainly introduces the clinical efficacy of TCM formulas for HPAG, as well as active ingredient and pharmacological mechanisms of herbs. What's more, this review puts forward potential prospects for future research. CONCLUSION: These research works have shown the therapeutic benefits of TCM in the treatment of HPAG. The development of TCM with more specific functions and practical data will not only become a significant trend in the world market but also have an irreplaceable role in the future treatment of HPAG. More continued researches should be undertaken in the future.

FBPAII and rpoBC, the Two Novel Secreted Proteins Identified by the Proteomic Approach from a Comparative Study between Antibiotic-Sensitive and Antibiotic-Resistant Helicobacter pylori-Associated Gastritis Strains.

Helicobacter pylori infection is the leading cause of chronic gastritis, which can develop into gastric cancer. Eliminating H. pylori infection with antibiotics achieves the prevention of gastric cancer. Currently, the prevalence of H. pylori resistance to clarithromycin and metronidazole, and the dual resistance to metronidazole and clarithromycin (C_R, M_R, and C/M_R, respectively), remains at a high level worldwide. As a means of exploring new candidate proteins for the management of H. pylori infection, secreted proteins from antibiotic-susceptible and antibiotic-resistant H. pylori-associated gastritis strains were obtained by in-solution tryptic digestion coupled with nano-liquid chromatography tandem mass spectrometry (nano-LC-MS/MS). A total of 583, 582, 590, and 578 differential expressed proteins were identified from C_R, M_R, C/M_R, and antibiotic-sensitive strain (S_S) samples, respectively. Of these, 23 overlapping proteins were found by Venn diagram analysis. Based on heat map analyses, the most and least differing protein expressions were observed from C/M_R strains and S_S strains, respectively. Of the proteins secreted by the S_S strain, only nine were found. After predicting the protein interaction with metronidazole and clarithromycin via the STITCH database, the two most interesting proteins were found to be rpoBC and FBPAII. After quantitative real-time reverse transcription PCR (qRT-PCR) analysis, a downregulation of rpoB from M_R strains was observed, suggesting a relationship of rpoB to metronidazole sensitivity. Inversely, an upregulation of fba from C_R, M_R, and C/M_R strains was noticed, suggesting the paradoxical expression of FBPAII and the fba gene. This report is the first to demonstrate the association of these two novel secreted proteins, namely, rpoBC and FBPAII, with antibiotic-sensitive H. pylori-associated gastritis strains.

Effects of polygonum capitatum on helicobacter pylori associated gastritis through the regulation of acetyla-tion of NF-κB by SIRT-1 / 医学研究生学报

Objective The activation of NF-kappa B (NF-κB) signaling pathway plays an important role in the development of helicobacter pylori associated gastritis (HAG). The article aimed to investigate the effects of polygonum capitatum on the treatment of HAG in NF-κB signaling pathway and observe whether the regulation of NF-κB acetylation by silent information regulator 1 (SIRT1) affects the therapeutic effects of HAG. Methods The immortalized human gastric epithelial cells (GES-1) were cultured and the H.pylori stand- ard strain ATCC700392 was used for the replication of HAG cell model by 100∶1. The cells were divided into model group,drug group and normal control group. Cells were treated with 80 μg/mL in drug group,H.pylori and GES-1 were cultured together in model group and untreated GES-1 cells were taken as control group. Real time PCR was used to detect the mRNA levels of SIRT1,NF-κB/p65 and TNF-α. Western blotting was used to detect the expression levels of SIRT1,NF-κB/p65 and its acetylated protein in the total protein,as well as the expression levels of SIRT1 and NF-κB/p65 in cytoplasm and nuclear protein. Results At 12 h after the infection of H. pylori,the level of TNF-α in the supernatant was higher than that in the normal control group(P<0.05). The expression of SIRT1 de-creased in the cytoplasm of model group,while the expression levels of NF-κB/p65,acetyl-NF-κB p65(Lys310) and TNF-α in the nu-cleus increased (P<0.05). But after the treatment of polygonum capitatum,the expression of SIRT1 in the nucleus increased(P<0.05) while the expression of NF-κB/p65,acetyl-NF-κB p65(Lys310) and TNF-α decreased (P<0.05). Conclusion Polygonum capita-tum can activate the SIRT1 in the nucleus,which makes activated NF-κB/p65 in the nucleus carry out deacetylation modification in or-der to antagonize the cell damage induced by H.pylori.