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      Modular Characteristics and Mechanism of Action of Herbs for Endometriosis Treatment in Chinese Medicine: A Data Mining and Network Pharmacology–Based Identification

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          Abstract

          Endometriosis is a common benign disease in women of reproductive age. It has been defined as a disorder characterized by inflammation, compromised immunity, hormone dependence, and neuroangiogenesis. Unfortunately, the mechanisms of endometriosis have not yet been fully elucidated, and available treatment methods are currently limited. The discovery of new therapeutic drugs and improvements in existing treatment schemes remain the focus of research initiatives. Chinese medicine can improve the symptoms associated with endometriosis. Many Chinese herbal medicines could exert antiendometriosis effects via comprehensive interactions with multiple targets. However, these interactions have not been defined. This study used association rule mining and systems pharmacology to discover a method by which potential antiendometriosis herbs can be investigated. We analyzed various combinations and mechanisms of action of medicinal herbs to establish molecular networks showing interactions with multiple targets. The results showed that endometriosis treatment in Chinese medicine is mainly based on methods of supplementation with blood-activating herbs and strengthening qi. Furthermore, we used network pharmacology to analyze the main herbs that facilitate the decoding of multiscale mechanisms of the herbal compounds. We found that Chinese medicine could affect the development of endometriosis by regulating inflammation, immunity, angiogenesis, and other clusters of processes identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The antiendometriosis effect of Chinese medicine occurs mainly through nervous system–associated pathways, such as the serotonergic synapse, the neurotrophin signaling pathway, and dopaminergic synapse, among others, to reduce pain. Chinese medicine could also regulate VEGF signaling, toll-like reporter signaling, NF-κB signaling, MAPK signaling, PI3K-Akt signaling, and the HIF-1 signaling pathway, among others. Synergies often exist in herb pairs and herbal prescriptions. In conclusion, we identified some important targets, target pairs, and regulatory networks, using bioinformatics and data mining. The combination of data mining and network pharmacology may offer an efficient method for drug discovery and development from herbal medicines.

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          FunRich: An open access standalone functional enrichment and interaction network analysis tool.

          As high-throughput techniques including proteomics become more accessible to individual laboratories, there is an urgent need for a user-friendly bioinformatics analysis system. Here, we describe FunRich, an open access, standalone functional enrichment and network analysis tool. FunRich is designed to be used by biologists with minimal or no support from computational and database experts. Using FunRich, users can perform functional enrichment analysis on background databases that are integrated from heterogeneous genomic and proteomic resources (>1.5 million annotations). Besides default human specific FunRich database, users can download data from the UniProt database, which currently supports 20 different taxonomies against which enrichment analysis can be performed. Moreover, the users can build their own custom databases and perform the enrichment analysis irrespective of organism. In addition to proteomics datasets, the custom database allows for the tool to be used for genomics, lipidomics and metabolomics datasets. Thus, FunRich allows for complete database customization and thereby permits for the tool to be exploited as a skeleton for enrichment analysis irrespective of the data type or organism used. FunRich (http://www.funrich.org) is user-friendly and provides graphical representation (Venn, pie charts, bar graphs, column, heatmap and doughnuts) of the data with customizable font, scale and color (publication quality).
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            Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi).

            Astragalus membranaceus is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The current paper reviews the botanical characteristics, phytochemistry, and pharmacology of Astragali Radix. Information on Astragali Radix was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI, and Web of Science) as well as from libraries and local books. More than 100 compounds, including flavonoids, saponins, polysaccharides, and amino acids, have so far been identified, and the various biological activities of the compounds have been reported. As an important traditional Chinese medicine, further studies on Astragali Radix can lead to the development of new drugs and therapies for various diseases. The improvement of its utilization should be studied further.
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              How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

              Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                06 March 2020
                2020
                : 11
                : 147
                Affiliations
                [1] 1The Second Clinical College of Guangzhou University of Chinese Medicine , Guangzhou, China
                [2] 2Guangzhou University of Chinese Medicine , Guangzhou, China
                [3] 3Department of Big Medical Data, Second Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                [4] 4Department of Gynecology, Second Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                [5] 5Team of Application of Chinese Medicine in Perioperative Period, Second Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou, China
                Author notes

                Edited by: Sheng-Teng Huang, China Medical University Hospital, Taiwan

                Reviewed by: Ben-Chang Shia, Taipei Medical University, Taiwan; Jing Zhao, Shanghai University of Traditional Chinese Medicine, China; Hong Nie, Jinan University, China

                *Correspondence: Xuefang Liang, liangxuefang2006@ 123456126.com ; Lixing Cao, lixingcao@ 123456126.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work

                Article
                10.3389/fphar.2020.00147
                7069061
                32210799
                d8bbc23f-185d-4a73-846d-93473d33d6bd
                Copyright © 2020 Zheng, Wu, Gu, Weng, Wang, Wang, Liang and Cao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 May 2019
                : 04 February 2020
                Page count
                Figures: 9, Tables: 6, Equations: 0, References: 105, Pages: 43, Words: 15491
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                medicinal herb,data mining,network analysis,bioinformatics,network pharmacology,endometriosis

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