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Gene & Protein in Disease                                  A prediction on how Epimedii herba treat periodontitis




            3 School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China
            4 Medical Center of Hip, Luoyang Orthopedic-Traumatological Hospital, Luoyang, Henan, China
            5 Henan International Joint Laboratory for Nuclear Protein Regulation, Kaifeng, Henan, China



            1. Introduction                                    was conducted to reveal the action pathway of EH during
                                                               periodontitis treatment from a network pharmacology
            Periodontitis, one of the three common oral diseases,   perspective, explore the binding liability of EH ingredients
            has a high morbidity rate worldwide.  The progression   with key targets by molecular docking and dynamics, and
                                           1
            of periodontitis not only affects the periodontal tissue   provide a specific basis for periodontitis treatment.
            but also induces or exacerbates systemic diseases such
            as diabetes, cardiovascular disease, and rheumatoid   2. Methods
                   2-5
            arthritis.  Current therapy to control the progression
            of periodontitis comprises basic treatments such as   2.1. Collection of the active compounds and active
            supragingival and subgingival scaling as well as antibiotic   targets of EH
            and surgical treatments.  Nevertheless, there exists a risk of   The traditional Chinese medicine systems pharmacology
                               6
            increased bacterial resistance and possible toxic side effects   database and analysis platform (TCMSP) was used to
            during antibiotic treatment.  Therefore, it is important to   explore EH-active compounds. Oral bioavailability (OB) of
                                  7
            develop new therapeutic strategies and explore alternative   ≥30% and drug-likeness (DL) of ≥0.18 were used to filter the
            anti-inflammatory drugs that can better control and treat   active compounds, which are the key factors for evaluating
            periodontitis.                                     absorption, distribution, metabolism, and excretion. OB of
                                                               ≥30% indicated that the drugs had better OB, and DL of
              Traditional Chinese medicine (TCM) can regulate the
            body’s own immunity and ameliorate patient symptoms   ≥0.18 indicated that the compounds had better solubility,
                                                               chemical stability, and drug-like properties. Finally, the
            but has certain side effects. 8-10   Epimedii herba  (EH)   targets of the compounds were obtained using the UniProt
            (common name: Yin-yang-huo in China), a herbaceous   (https://www.uniprot.org) database.
            plant widely distributed in Asia and Europe, has been used
            alone or with other TCM to treat various diseases such as   2.2. Collection of disease targets
            osteoporosis and sexual dysfunction for >2000  years. 11,12
            Modern pharmacological studies have confirmed that   “Periodontitis” was used as the keyword to input in the
                                                               GeneCards database (https://www.genecards.org), OMIM
            EH exhibits numerous pharmacological activities, such   database (https://omim.org), DrugBank database (https://
            as anti-inflammatory, immune regulatory, and antitumor   www.drugbank.ca),  TTD  (https://db.idrblab.net/ttd/),
            effects. 13-15  Existing data have shown that the extracts of   and CTD (http://ctdbase.org/) to explore the targets of
            EH, icariin, and kaempferol can significantly reduce the   periodontitis. Then, using humans as the screening condition,
            inflammatory response. 16,17  Moreover, several studies have   the protein names of the disease targets were turned into gene
            reported the potential of EH for treating periodontitis,   names using the UniProt database. The GEO database was
            which may contribute to the proliferation of human   also used to screen the targets related to periodontitis. Data
            periodontal ligament cells and regeneration of alveolar   correction was performed in Perl, differential gene analysis
            bone. 18,19  However,  after entering the  human body,  the   was performed in the Limma package in R software (4.2.2),
            pathways and modes of actions of EH are diverse because   and the volcano map and heatmap were plotted using the
            of multicomponent and multitarget regulation; hence,   ggplot2 package. p-values of <0.05 and fold-change values of
            it is necessary to further explore the mechanism of core   >2 were considered to indicate significant differences. 22
            ingredients and targets for the treatment of periodontitis. 20,21
              Recently, network pharmacology has received      2.3. Screening of intersection targets
            increasing attention in TCM research as it can reveal the   The website https://bioinfogp.cnb.csic.es/tools/venny/
            interaction mechanisms between the targets and active   was used to construct a Venn  diagram and obtain the
            ingredients  of  TCM  through  bioinformatics  technology,   intersection targets.
            which  systematically links  drugs  with diseases to
            identify the mode of action of TCM on diseases from the   2.4. Construction of the EH ingredient–target
            network interaction level. However, the pharmacological   interaction network
            mechanism of EH during periodontitis treatment has   An interaction network was constructed between
            not been exhaustively elucidated. Therefore, this study   the ingredients of EH and potential targets using


            Volume 3 Issue 4 (2024)                         2                               doi: 10.36922/gpd.4427
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