[Research and development practice of traditional Chinese medicine based on network target theory and technology].

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.

Uncovering the mechanisms of Yi Qi Tong Qiao Pill in the treatment of allergic rhinitis based on Network target analysis.

OBJECTIVE: The purpose of this study is to reveal the mechanism of action of Yi Qi Tong Qiao Pill (YQTQP) in the treatment of allergic rhinitis (AR), as well as establish a paradigm for the researches on traditional Chinese medicine (TCM) from systematic perspective. METHODS: Based on the data collected from TCM-related and disease-related databases, target profiles of compounds in YQTQP were calculated through network-based algorithms and holistic targets of TQTQP was constructed. Network target analysis was performed to explore the potential mechanisms of YQTQP in the treatment of AR and the mechanisms were classified into different modules according to their biological functions. Besides, animal and clinical experiments were conducted to validate our findings inferred from Network target analysis. RESULTS: Network target analysis showed that YQTQP targeted 12 main pathways or biological processes related to AR, represented by those related to IL-4, IFN-γ, TNF-α and IL-13. These results could be classified into 3 biological modules, including regulation of immune and inflammation, epithelial barrier disorder and cell adhesion. Finally, a series of experiments composed of animal and clinical experiments, proved our findings and confirmed that YQTQP could improve related symptoms of AR, like permeability of nasal mucosa epithelium. CONCLUSION: A combination of Network target analysis and the experimental validation indicated that YQTQP was effective in the treatment of AR and might provide a new insight on revealing the mechanism of TCM against diseases. Trial registration Name of the registry: Chinese Clinical Trial Registry: Trial registration number: ChiCTR-TRC-13,003,137: Date of registration: Registered 29 March 2013 - Retrospectively registered: URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=6422 .

Repositioning of clinically approved drug Bazi Bushen capsule for treatment of Aizheimer's disease using network pharmacology approach and in vitro experimental validation.

Aims: To explore the new indications and key mechanism of Bazi Bushen capsule (BZBS) by network pharmacology and in vitro experiment. Methods: The ingredients library of BZBS was constructed by retrieving multiple TCM databases. The potential target profiles of the components were predicted by target prediction algorithms based on different principles, and validated by using known activity data. The target spectrum of BZBS with high reliability was screened by considering the source of the targets and the node degree in compound-target (C-T) network. Subsequently, new indications for BZBS were predicted by disease ontology (DO) enrichment analysis and initially validated by GO and KEGG pathway enrichment analysis. Furthermore, the target sets of BZBS acting on AD signaling pathway were identified by intersection analysis. Based on STRING database, the PPI network of target was constructed and their node degree was calculated. Two Alzheimer's disease (AD) cell models, BV-2 and SH-SY5Y, were used to preliminarily verify the anti-AD efficacy and mechanism of BZBS in vitro. Results: In total, 1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula, and 1320 BZBS targets with high confidence were predicted. Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treatment of AD. GO and KEGG enrichment results provide a preliminary verification of this point. Among them, 113 functional targets of BZBS belong to AD pathway. A PPI network containing 113 functional targets and 1051 edges for the treatment of AD was constructed. In vitro experiments showed that BZBS could significantly reduce the release of TNF-α and IL-6 and the expression of COX-2 and PSEN1 in Aß25-35-induced BV-2 cells, which may be related to the regulation of ERK1/2/NF-κB signaling pathway. BZBS reduced the apoptosis rate of Aß25-35 induced SH-SY5Y cells, significantly increased mitochondrial membrane potential, reduced the expression of Caspase3 active fragment and PSEN1, and increased the expression of IDE. This may be related to the regulation of GSK-3ß/ß-catenin signaling pathway. Conclusions: BZBS formula has a potential use in the treatment of AD, which is achieved through regulation of ERK1/2, NF-κB signaling pathways, and GSK-3ß/ß-catenin signaling pathway. Furthermore, the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action. The study lays a foundation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Network pharmacology- and molecular docking-based investigation of the therapeutic potential and mechanism of daucosterol against multiple myeloma.

Background: Some studies have shown that daucosterol has potential anti-tumor activity, but its therapeutic effect on multiple myeloma (MM) has not been reported. This study aimed to evaluate the therapeutic effect daucosterol against MM and explore its possible mechanism through network pharmacology. Methods: We collected daucosterol and approved drugs for MM, and their potential target profiles were obtained. We used 2 major methods to collect the gene sets related to the physiological process of MM. Based on the protein-protein interaction (PPI) network in the STRING database, the correlation between the therapeutic targets of daucosterol and MM-related genes was calculated by using the random walk with restart (RWR) algorithm to systematically evaluate the therapeutic potential of daucosterol for MM. On this basis, through intersection analysis, the potential targets of daucosterol in treating MM were identified, and the signaling pathways were mined. Furthermore, the key targets were identified. Finally, the regulatory relationship between the predicted daucosterol and potential targets was verified by molecular docking method, and the interaction mode between daucosterol and key targets was analyzed. Results: A total of 13 approved drugs reported to treat MM were retrieved from the DrugBank database. A total of 35 potential targets of daucosterol were obtained, including 8 known targets and 27 newly predicted targets. In the PPI network, the target of daucosterol was significantly correlated with MM-related genes, indicating that it has therapeutic potential for MM. A total of 18 therapeutic targets for MM were obtained, which were significantly enriched in the FoxO signaling pathway, prostate cancer, the PI3K-Akt signaling pathway, insulin resistance, the AMPK signaling pathway, and pathways related to the regulation of TP53. The core targets were HSP90AA1, MDM2, GSK3B, AKT3, PRKAA1, and PRKAB1. Molecular docking suggested that daucosterol had potential direct regulatory effects on 13 of the 18 predicted targets. Conclusions: This study highlights the use of daucosterol as a promising therapeutic drug for MM treatment. These data provide new insights into the potential mechanism of daucosterol in the treatment of MM, which may provide references for subsequent research and even the clinical treatment.

Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Weifuchun capsule (WFC) is a traditional Chinese patent medicine for chronic atrophic gastritis (CAG) in clinic. However, the mechanism of action of WFC for CAG still remains unclear due to its complex composition. AIM OF THE STUDY: The study was projected to uncover the mechanism of action of WFC and the corresponding pharmacodynamic substance of WFC against CAG as well as providing a standard example for the research of traditional Chinese medicine (TCM) from the perspective of the network and the system. MATERIALS AND METHODS: We identified the compounds of WFC through LC-MS/MS analysis and performed a systematic network targets analysis for WFC in the treatment of CAG which thoroughly described the mechanism of action of WFC for CAG. Based on analysis integrating omics data and algorithms, we focused on the specific immune regulatory role of WFC in the treatment of CAG, especially on a hub pathway, Toll-like receptor signaling pathway and thus deciphered the role of WFC in immune regulation, anti-inflammation and mediation of HES6. In experiments part, MNNG-GES-1-cell line and rat models were used to validate our findings. RESULTS: In this study, compounds of WFC are identified through LC‒MS/MS and network target analysis is performed to dissect the specific immunoregulatory effect as well as mediation of HES6, a newly discovered biomolecule related to gastritis carcinoma progression, of WFC on CAG through the Toll-like receptor signaling pathway. Based on cell line and rat models, we verify the mechanism of action of WFC for CAG in inhibiting inflammatory cytokines, regulating immune cells like T cells and macrophages, related genes including TLR2 and CD14. It is also validated that WFC inhibits the expression of HES6 (P < 0.05). CONCLUSION: Based on the combination of computational strategy and experiments, our study offers a comprehensive analysis to reveal the role of WFC in regulating immune response, inhibiting inflammation in the treatment of CAG, and provides a standard example for the research of TCM from the perspective of the network and the system.

Research and development practice of traditional Chinese medicine based on network target theory and technology / 中国中药杂志

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.