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A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis.

ABSTRACT: Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs participate in the regulations of 24 pathways associated with RA and that 5 herbs in the 7 herbs and 25 compounds in the 5 herbs participate in the regulation of hsa05323 (rheumatoid arthritis). The results indicated that all herbs in LZTB and some compounds in those herbs participate in the treatment of RA; 25 compounds are main active ingredients and hsa05323 (rheumatoid arthritis) is the major pathway in the treatment of RA. We have also found that three pathways (inflammatory mediator regulation of TRP channels, PPAR signaling pathway, and mTOR signaling pathway) might have some effect on the treatment of RA.

SUBMITTER: Huang A

PROVIDER: S-EPMC6354157 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis.

Huang An A Fang Gang G Pang Yuzhou Y Pang Zongran Z

Evidence-based complementary and alternative medicine : eCAM 20190117

Longzuan Tongbi Formula (LZTB) is an effective proved prescription in Zhuang medicine for treating active rheumatoid arthritis (RA). However, its active ingredients, underlying targets, and pharmacological mechanism are still not clear in treating RA. We have applied network pharmacology to study LZTB and found that 8 herbs in LZTB and 67 compounds in the 8 herbs are involved in the regulation of RA-related genes; we have conducted pathway analysis of overlapping genes and found that 7 herbs par ...[more]

PMID: 30792744

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Project description:Purpose:We explored the mechanism of Shugan Jianpi Formula (SGJPF) and its effective components for the treatment of liver fibrosis (LF). Materials and Methods:We collected the active ingredients in SGJPF through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and screened the effective components by absorption, distribution, metabolism, and excretion. Herb-associated target proteins were predicted and screened based on the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Search Tool for Interactions of Chemicals databases. LF-associated target proteins were predicted and screened based on the Online Mendelian Inheritance in Man® Database and Comparative Toxicogenomics Database. Common genes with LF and herbs were selected, and Cytoscape 3.5.1 software was used to construct an herb pathway and component-LF common target network. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to build a protein-protein interaction, and quantitative PCR was used to verify the related target genes. Finally, clusterProfiler was applied for the analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results:The pharmacological network contained 252 active compounds (e.g., Astragaloside A, saikosaponin, linoleic acid, and Poria acid A), 84 common target genes, and 94 significant signaling pathways. Among them, interleukin 6 (IL-6), tumor protein 53 p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), AKT1, IL-1?, and the nucleotide-binding and oligomerization domain-like receptor and Janus kinase-signal transducer and activator of transcription signaling pathways were selected as the critical target gene and critical signal pathway, respectively. Conclusion:The mechanisms of SGJPF in protecting against LF include the regulation of multiple targets such as IL-6, TP53, PTGS2, and AKT1. These target proteins affect LF through various signal transduction pathways.

Project description:BackgroundAcute-on-chronic liver failure (ACLF) is a clinical syndrome with acute jaundice and coagulation dysfunction caused by various inducements on the basis of chronic liver disease. Western medical treatment is limited. Previous studies have confirmed that Jieduan-Niwan Formula (JDNW Formula), an empirical prescription for the treatment of ACLF, can inhibit inflammation and resist hepatocyte apoptosis. However, potential targets and mechanisms still need to be explored.MethodsIn this study, network pharmacological analysis was performed to investigate the key components and potential mechanisms of JDNW Formula treating ACLF. Firstly, we predicted the potential active ingredients of JDNW Formula and the corresponding potential targets through TCMSP, BATMAN-TCM platform, and literature supplement. Then, the ACLF targets database was built using OMIM, DisGeNET, and GeneCard database. Based on the matching targets between JDNW Formula and ACLF, the PPI network was constructed for MCODE analysis and common targets were enriched by Metascape. Furthermore, the ACLF rat model was used to verify the potential mechanism of JDNW Formula in treating ACLF.Results132 potential bioactive components of JDNW Formula and 168 common targets were obtained in this study. The enrichment analysis shows that the AMPK signaling pathway was associated with the treating effects of JDNW Formula. Quercetin was hypothesized to be the key bioactive ingredient in JDNW Formula and has a good binding affinity to AMPK based on molecular docking verification. JDNW Formula and quercetin were verified to treat ACLF by regulating the AMPK/PGC-1α signaling pathway as a prediction.ConclusionThe study predicted potential mechanisms of JDNW Formula in the treatment of ACLF, involving downregulation of inflammatory factor expression, antioxidant stress, and inhibition of hepatocyte apoptosis. JDNW Formula may improve mitochondrial quality in ACLF via the AMPK signaling pathway, which serves as a guide for further study.

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A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis.

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A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis.

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