Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification
Japanese <i>Ardisia</i> is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese <i>Ardisia</i> and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynam...
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MDPI AG
2022-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/12/1457 |
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| author | Tian Fu Yifei Chen Junkui Li Peili Zhu Huajuan He Wei Zhang Ken Kin Lam Yung Wei Wu |
| author_facet | Tian Fu Yifei Chen Junkui Li Peili Zhu Huajuan He Wei Zhang Ken Kin Lam Yung Wei Wu |
| author_sort | Tian Fu |
| collection | DOAJ |
| description | Japanese <i>Ardisia</i> is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese <i>Ardisia</i> and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese <i>Ardisia</i> in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese <i>Ardisia</i> were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese <i>Ardisia</i> were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound–target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese <i>Ardisia</i> mainly involved DNA–binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE–RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese <i>Ardisia</i>. Molecular docking showed that quercetin and kaempferol have good binding to <i>AKT1</i>, <i>IL6</i>, <i>VEGFA</i>, and <i>CASP3</i>. Animal experiments demonstrated that Japanese <i>Ardisia</i> could increase the expression of <i>AKT1</i> and decrease the expression of <i>CASP3</i> protein, as well as <i>IL-6</i>, in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese <i>Ardisia</i> in the treatment of AIH. At the same time, the effectiveness of Japanese <i>Ardisia</i> in treating AIH was verified by animal experiments. |
| first_indexed | 2024-03-09T15:59:50Z |
| format | Article |
| id | doaj.art-ec43a57f71cf490ea65aefa0b445b334 |
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| language | English |
| last_indexed | 2024-03-09T15:59:50Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-ec43a57f71cf490ea65aefa0b445b3342023-11-24T17:15:30ZengMDPI AGPharmaceuticals1424-82472022-11-011512145710.3390/ph15121457Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental VerificationTian Fu0Yifei Chen1Junkui Li2Peili Zhu3Huajuan He4Wei Zhang5Ken Kin Lam Yung6Wei Wu7School of Pharmacy, Guilin Medical University, Guilin 541199, ChinaSchool of Pharmacy, Guilin Medical University, Guilin 541199, ChinaDepartment of Biology, Hong Kong Baptist University, Hong Kong 999077, ChinaDepartment of Biology, Hong Kong Baptist University, Hong Kong 999077, ChinaSchool of Pharmacy, Guilin Medical University, Guilin 541199, ChinaSchool of Pharmacy, Guilin Medical University, Guilin 541199, ChinaDepartment of Biology, Hong Kong Baptist University, Hong Kong 999077, ChinaSchool of Pharmacy, Guilin Medical University, Guilin 541199, ChinaJapanese <i>Ardisia</i> is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese <i>Ardisia</i> and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese <i>Ardisia</i> in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study. Following that, the effects of Japanese <i>Ardisia</i> were evaluated using the concanavalin A (Con A)-induced acute liver injury rat model. The active ingredients and targets of Japanese <i>Ardisia</i> were searched using the Traditional Chinese Medicine Systems Pharmacology database, and hepatitis-related therapeutic targets were identified through GeneCards and Online Mendelian Inheritance in Man databases. A compound–target network was then constructed using Cytoscape software, and enrichment analysis was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular docking technology was used to simulate the docking of key targets, and the AIH rat model was used to validate the expression of key targets. Nineteen active chemical components and 143 key target genes were identified. GO enrichment analysis revealed that the treatment of AIH with Japanese <i>Ardisia</i> mainly involved DNA–binding transcription factor binding, RNA polymerase II-specific DNA transcription factor binding, cytokine receptor binding, receptor-ligand activity, ubiquitin-like protein ligase binding, and cytokine activity. In the KEGG enrichment analysis, 165 pathways were identified, including the lipid and atherosclerotic pathway, IL-17 signaling pathway, TNF signaling pathway, hepatitis B pathway, and the AGE–RAGE signaling pathway in diabetic complications. These pathways may be the key to effective AIH treatment with Japanese <i>Ardisia</i>. Molecular docking showed that quercetin and kaempferol have good binding to <i>AKT1</i>, <i>IL6</i>, <i>VEGFA</i>, and <i>CASP3</i>. Animal experiments demonstrated that Japanese <i>Ardisia</i> could increase the expression of <i>AKT1</i> and decrease the expression of <i>CASP3</i> protein, as well as <i>IL-6</i>, in rat liver tissues. This study identified multiple molecular targets and pathways for Japanese <i>Ardisia</i> in the treatment of AIH. At the same time, the effectiveness of Japanese <i>Ardisia</i> in treating AIH was verified by animal experiments.https://www.mdpi.com/1424-8247/15/12/1457Japanese <i>Ardisia</i>autoimmune hepatitisnetwork pharmacologymolecular dockingunderlying mechanism |
| spellingShingle | Tian Fu Yifei Chen Junkui Li Peili Zhu Huajuan He Wei Zhang Ken Kin Lam Yung Wei Wu Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification Pharmaceuticals Japanese <i>Ardisia</i> autoimmune hepatitis network pharmacology molecular docking underlying mechanism |
| title | Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification |
| title_full | Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification |
| title_fullStr | Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification |
| title_full_unstemmed | Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification |
| title_short | Exploring the Effective Components and Mechanism of Action of Japanese <i>Ardisia</i> in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification |
| title_sort | exploring the effective components and mechanism of action of japanese i ardisia i in the treatment of autoimmune hepatitis based on network pharmacology and experimental verification |
| topic | Japanese <i>Ardisia</i> autoimmune hepatitis network pharmacology molecular docking underlying mechanism |
| url | https://www.mdpi.com/1424-8247/15/12/1457 |
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