ETHNOPHARMACOLOGICAL RELEVANCEYupingfeng San (YPFS) is a classic rousing prescription in Chinese medicine, with widly clinical application and remarkably curative effect. It consists of three herbs named Astragalus mongholicus Bunge (Huangqi), Atractylodes rubra Dekker (Baizhu) and Saposhnikovia divaricata (Turcz.) Schischk. (Fangfeng), and has a variety of pharmacological activities including immune regulation, antioxidant, anti-tumor, regulation of cytokines, etc. AIM OF THE STUDY: It has been proved that YPFS exerts its anti-tumor effect through enhancing the systemic and local immune responses in tumor patients, moreover, it has the direct tumor-suppressing effect and can reduce the adverse reactions caused by radiotherapy and chemotherapy drugs. Therefore, in this study, we explored the potential anti-HCC mechanism of YPFS based on HTS² technology and systems pharmacology, aiming to provide a scientific basis for the clinical application of YPFS and a new strategy for Chinese medicine research.MATERIALS AND METHODSIn this study, systems pharmacology plus high throughput sequencing-based high throughput screening (HTS²) technology, and experimental validation were used to investigate the therapeutic mechanisms and the chemical basis of YPFS in HCC treatment. Firstly, the potential therapeutic targets and signaling pathways of YPFS in the treatment of HCC were obtained through systems pharmacology. Subsequently, HTS² technology combined with PPI network analysis were used to reveal potential therapeutic targets. Finally, the anti-HCC effects and underlying mechanisms of YPFS were further verified in vitro in human hepatocellular carcinoma cell lines. Moreover, the possible chemical basis was explored by drug target verification and molecular docking technology.RESULTSIn total, 183 active ingredients were predicted by YPFS screening and 49 anti-HCC targets were further identified. Most of these targets were enriched into the "MAPK pathway", and the expression of 37 genes was significantly changed after herb treatment. Among them, 5 key targets, including VEGFA, GRB2, JUN, PDGFRB and CDC42, were predicted by protein-protein interaction (PPI) network analysis. According to our results, YPFS inhibited the proliferation, induced the apoptosis and caused cell cycle arrest of HCC cells. In addition, YPFS significantly reduced P38 gene expression. Fangfeng, one of the three herbs in YPFS, significantly down-regulated the expression of more target genes than that of the other two herbs. Lastly, as revealed by molecular docking analysis, 4'-O-glucosyl-5-O-methylvisamminol, an active ingredient identified in Fangfeng, showed a high affinity for P38.CONCLUSIONTaken together, this study shows that YPFS possesses the activities of anti-proliferation and pro-apoptosis in treating HCC, which are achieved by inhibiting the MAPK signaling pathway. P38 is one of the critical targets of YPFS in treating HCC, which may be directly bound and inhibited by 4'-O-glucosyl-5-O-methylvisamminol, a compound derived from YPFS.

2023-02-01·Current Pharmaceutical Design

Network Pharmacology and Integrated Molecular Docking Study on the Mechanism of the Therapeutic Effect of Fangfeng Decoction in Osteoarthritis

Article

作者: Wang, Wenqiao ; Si, Hongzong ; Li, Min ; Jiang, Zehui

Background:At present, there are no effective pharmacologic therapies for attenuating the course of osteoarthritis (OA) in humans and current therapies are geared to mitigating symptoms. Fangfeng decoction (FFD) is a traditional Chinese medicine prescribed for the treatment of OA. In the past, FFD has achieved positive clinical outcomes in alleviating the symptoms of OA in China. However, its mechanism of action has not yet been clarified.Objective:The objective of this study is to investigate and explore the mechanism of FFD and how the compound interacts with the target of OA; network pharmacology and molecular docking methods were applied in this study.Methods:The active components of FFD were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database according to the inclusion criteria as oral bioactivity (OB) ≥30% and drug likeness (DL) ≥0.18. Then, gene name conversion was performed through the UniProt website. The related target genes of OA were obtained from the Genecards database. Core components, targets, and signaling pathways were obtained through compound-target-pathway (C-T-P) and protein–protein interaction (PPI) networks were built using Cytoscape 3.8.2 software. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of gene targets. The interactions of key targets and components were analyzed by molecular docking in Sybyl 2.1 software.Results:A total of 166 potential effective components,148 FFD-related targets, and 3786 OA-related targets were obtained. Finally, 89 common potential target genes were confirmed. Pathway enrichment results showed that HIF-1 and CAMP signaling pathways were considered key pathways. The screening of core components and targets was achieved through the CTP network. The core targets and active components were obtained according to the CTP network. The molecular docking results showed that quercetin, medicarpin, and wogonin of FFD could bind to NOS2, PTGS2, and AR, respectively.Conclusion:FFD is effective in the treatment of OA. It may be caused by the effective binding of the relevant active components of FFD to the targets of OA.

2023-01-01·Combinatorial Chemistry & High Throughput Screening4区 · 医学

Exploring the Core Prescription and Underlying Mechanism of Traditional Chinese Medicine in Treating Allergic Rhinitis in Children: A Real- World Study Based on an Illustrious Senior Traditional Chinese Medicine Practitioner

4区 · 医学

Article

作者: He, Yu ; Wang, Junhong ; Yan, Yurou ; Wang, Yuhan ; Luo, Changyong ; He, Bing ; Gu, Xiaohong

Background:Traditional Chinese medicine (TCM) is widely used to treat allergic rhinitis (AR) in China, especially in children. However, due to the complicated composition rules and unclear underlying mechanisms, effective herbal prescriptions’ popularization and application are limited.Purpose:This study tried to detect the core prescription of herbs in treating AR in children, reveal its mechanism based on the ingredients’ network, and explore the main signaling pathways.Methods:We screened medical records of children patients with AR who were treated by TCM in DongZhiMen Hospital from Aug 2009 to Jan 2020 and adopted a descriptive analysis method on herbal characteristics. We used association rules to mine core prescriptions and used network pharmacology to establish the ingredient-target-pathway network through online databases and TCMSP, Genecards, KEGG pathway, Excel, R-Studio, and Cytoscape software.Results:The analysis of 1,092 clinical visits highlighted that the principle of formulating prescription was as follows: ‘pungent and warm herbs were used more frequently while cold-natured herbs were paid equal attention as warm-natured herbs.’ The core prescription was formed by FangFeng, BaiZhi, CangErzi, and ChanTui. These herbs covered 130 underlying targets and 141 signaling pathways of AR, which mainly had an effect on signal transduction and immunoregulation.Conclusion:The core prescription based on these real-world clinical records includes FangFeng, BaiZhi, CangErzi, and ChanTui. It principally acts on targets of signal transduction pathways and immune pathways.

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