Cuihua Chen , Feiyan Chen , Ling Gu , Yucui Jiang , Zhichen Cai , Yunan Zhao , Lin Chen , Zhu Zhu , Xunhong Liu
{"title":"发现并验证 COX2 是 Apocyni Veneti Folium 中黄酮类化合物的靶标:对治疗肝损伤的意义。","authors":"Cuihua Chen , Feiyan Chen , Ling Gu , Yucui Jiang , Zhichen Cai , Yunan Zhao , Lin Chen , Zhu Zhu , Xunhong Liu","doi":"10.1016/j.jep.2024.117919","DOIUrl":null,"url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><p>Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified.</p></div><div><h3>Aim of the study</h3><p>This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets.</p></div><div><h3>Material and methods</h3><p>AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC–MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets.</p></div><div><h3>Results</h3><p>A total of 71 compounds were identified by LC–MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin.</p></div><div><h3>Conclusions</h3><p>COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.</p></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"326 ","pages":"Article 117919"},"PeriodicalIF":4.8000,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery and validation of COX2 as a target of flavonoids in Apocyni Veneti Folium: Implications for the treatment of liver injury\",\"authors\":\"Cuihua Chen , Feiyan Chen , Ling Gu , Yucui Jiang , Zhichen Cai , Yunan Zhao , Lin Chen , Zhu Zhu , Xunhong Liu\",\"doi\":\"10.1016/j.jep.2024.117919\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Ethnopharmacological relevance</h3><p>Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified.</p></div><div><h3>Aim of the study</h3><p>This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets.</p></div><div><h3>Material and methods</h3><p>AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC–MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets.</p></div><div><h3>Results</h3><p>A total of 71 compounds were identified by LC–MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin.</p></div><div><h3>Conclusions</h3><p>COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.</p></div>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\"326 \",\"pages\":\"Article 117919\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-02-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378874124002186\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378874124002186","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Discovery and validation of COX2 as a target of flavonoids in Apocyni Veneti Folium: Implications for the treatment of liver injury
Ethnopharmacological relevance
Apocyni Veneti Folium (AVF), a popular traditional Chinese medicine (TCM), is known for its effects in soothing the liver and nerves and eliminating heat and water. It is relevant from an ethnopharmacological perspective. Pharmacological research has confirmed its benefits on antihypertension, antihyperlipidemia, antidepression, liver protection, immune system boosting, antiaging, and diabetic vascular lesions. Previous studies have shown that flavonoids, the active ingredients, have a hepatoprotective effect. However, the exact mechanism has not been clarified.
Aim of the study
This study aimed to identify the active flavonoids in AVF and their corresponding targets for liver injury. Multiple methods were introduced to confirm the targets.
Material and methods
AVF compounds were analyzed using liquid chromatography-mass spectrometry (LC–MS). Then, network pharmacology was utilized to screen potential hepatoprotection targets of the compounds. An enzyme activity assay was performed to determine the effect of the compounds on the targets. Biolayer interferometry (BLI) was applied to confirm the direct interaction between the compounds and the targets.
Results
A total of 71 compounds were identified by LC–MS and 19 compounds and 112 shared targets were screened using network pharmacology. These common targets were primarily involved in the TNF signaling pathway, cancer pathways, hepatitis B, drug responses, and negative regulation of the apoptotic process. Flavonoids were the primary pharmacological substance basis of AVF. The cyclooxygenase 2 (COX2) protein was one of the direct targets of flavonoids in AVF. The enzyme activity assay and BLI-based intermolecular interactions demonstrated that the compounds astragalin, isoquercitrin, and hyperoside exhibited stronger inhibition of enzyme activity and a higher affinity with COX2 compared to epigallocatechin, quercetin, and catechin.
Conclusions
COX2 was preliminarily identified as a target of flavonoids, and the mechanism of the hepatoprotective effect of AVF might be linked to flavonoids inhibiting the activity of COX2. The findings can establish the foundation for future research on the traditional hepatoprotective effect of AVF on the liver and for clinical studies on liver disorders.
期刊介绍:
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.