MoLuoDan

Moluodan concentrated pill (MLD) is a traditional herbal formula used in China for the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism of action remains unclear.

The aim of this study was to investigate the therapeutic effect and mechanism of action of MLD in the treatment of CAG using network pharmacology and in vivo experiments.

The active compounds of MLD were determined using network pharmacology, utilizing various Chinese medicine databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Traditional Chinese Medicine Integrated Database, Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine, and a comprehensive database of Traditional Chinese Medicine on Immuno-Oncology. The compounds found in the root of Anemone altaica Fisch. were extracted from the China National Knowledge Infrastructure literature database. Additionally, the Swiss Target Prediction database and Similarity Ensemble Approach were employed to identify the potential targets of these components. CAG-related targets were gathered from the GeneCards and DisGeNET databases. Protein-protein interactions (PPIs) of the genes associated with the drug-disease crossover were examined, and a core PPI network was constructed using the STRING database (version 11.5) and Cytoscape (version 3.7.2). A gene-pathway network was established to identify significant target genes and pathways through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, based on these findings and existing data, the tumor necrosis factor (TNF) signaling pathway was selected for further validation through in vivo experiments.

A total of 724 active molecules in MLD yielded 961 identified target genes, of which 179 were found to be potentially associated with CAG. From the common targets, a PPI network revealed ten core targets. Enrichment analysis suggested that MLD may primarily target TNF and AKT in the treatment of CAG. Essential signaling pathways, such as the PI3K-AKT and TNF pathways, were found to be crucial for the therapeutic effects of MLD on CAG. Furthermore, potential interactions and crosstalk between these pathways were identified. Moreover, we confirmed that MLD effectively improved gastric mucosa atrophy and cellular ultrastructural damage, while increasing pepsinogen secretion and decreasing gastrin, somatostatin, and motilin levels. Subsequent molecular biology studies in rat models of CAG demonstrated that MLD treatment significantly reduced the expression levels of TNF-α, phosphatidylinositol 3'-kinase (PI3K), and phosphorylated Akt (P < 0.05). Notably, the expression of nuclear factor kappa-B (NF-κB) exhibited a contrasting trend (P < 0.05), potentially associated with the crucial tumor suppressor role of NF-κB p105.

This study provides evidence that MLD effectively alleviates stomach mucosal atrophy through modulation of the TNF/PI3K/AKT signaling pathway. These findings establish a solid theoretical foundation for the practical management of CAG.

To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions.

Patients aged 18–70 years diagnosed with moderate‐to‐severe atrophy and/or moderate‐to‐severe intestinal metaplasia, with or without low‐grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double‐blind, parallel‐controlled trial. The primary outcome was the improvement of global histological diagnosis at 1‐year follow‐up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia.

Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high‐dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high‐dose Moluodan. Moluodan was non‐inferior to folic acid (95% confidence interval: −9.2 to 12.5; P = 0.02). High‐dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug‐related serious adverse events were observed.

One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.