Abstract
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-1β, 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.
Highlights
Liver fibrosis (LF) is a pathological reaction of the liver to chronic liver injury [1]
11 types of herbs in the Shugan Jianpi Formula (SGJPF) contained 1048 compounds; detailed information about all compounds can be visualized in the Upset plot, which demonstrates the quantitative results of multiple interactive sets more effectively than the traditional Venn diagram [15]
Palmitic acid was in six types of herbs including Chaihu, Huangqi, Baizhu, Fuling, Targeted gene interleukin 6 (IL-6) tumor protein 53 p53 (TP53) AKT1 IL-1β
Summary
Liver fibrosis (LF) is a pathological reaction of the liver to chronic liver injury [1]. Liver injury leads to activation of hepatic stellate cells (HSCs) and an increase in extracellular matrix (ECM) synthesis and secretion. A large amount of ECM causes insufficient blood supply to the liver, and some HSCs are transformed into proliferative and contractile myofibroblasts, followed by the development of LF [2]. LF is reversible, there is no specific drug for the treatment of hepatic fibrosis. Traditional Chinese Medicine (TCM) has received an increasing amount of attention due to its notable effectiveness and low side effects. TCM has special advantages in antiliver fibrosis as it is characterized by holistic concepts and TCM syndrome differentiation and treatment [3]. Shugan Jianpi Formula (SGJPF), a classical TCM formula, consists of Baishao (BS, Paeoniae Radix Alba), Baizhu (BZ, Atractylodis Macrocephalae Rhizoma), Banlan Gen
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