{"title":"Multi-omics joint analysis reveals the mechanism underlying Chinese herbal Yougui Pill in the treatment of knee osteoarthritis.","authors":"Siyu Li, Yongju Yang, Yu Zhang, Fanyu He, Jie Chen, Yuanhe Fan, Hui Zhang, Xuefeng Guan","doi":"10.1016/j.jep.2024.119098","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Yougui Pill (YGP), originating from Jingyue Quanshu, comprises 10 traditional Chinese medicines (TCMs). This classic prescription is renowned for its ability to tonify the kidney, warm the kidney, promote yang, warm the interior, and dispel cold. YGP has proven effective in treating degenerative knee arthritis, osteoporosis, delayed fracture healing, and other orthopedic conditions, making it a widely used clinical prescription for knee osteoarthritis (KOA).</p><p><strong>Aim of the study: </strong>Although YGP is commonly used in clinical practice, its pharmacodynamic material basis and anti-arthritis mechanisms remain unclear. This study aims to comprehensively analyze the chemical constituents of YGP and elucidate its anti-arthritis mechanisms.</p><p><strong>Materials and methods: </strong>Ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry(ESI-Q TRAP-MS/MS) was used to identify the chemical constituents of YGP. The Hulth method was utilized to establish KOA rat model, and pathological examinations were performed to assess the anti-arthritis effects of YGP. Integrated metabolomics and transcriptomics analyses were conducted to explore the anti-arthritis mechanisms of YGP. Key targets were confirmed via immunohistochemistry.</p><p><strong>Results: </strong>A total of 1981 chemical components were identified in YGP, predominantly phenolic acids and flavonoids. Compared with the model group, 422 differentially expressed metabolites and 214 differentially expressed genes were identified, primarily involving the MAPK signaling pathway, FoxO signaling pathway, and PI3K-Akt pathway. YGP exerted an anti-osteoarthritis effect by inhibiting the excessive activation of the EGFR/ERT/FOS signaling pathway.</p><p><strong>Conclusions: </strong>TCM offers significant advantages in the treatment of KOA, addressing the shortcomings of current clinical medications. YGP displayed exceptional pharmacodynamic effects. This study elucidated its pharmacodynamic material basis and anti-osteoarthritis mechanisms, providing substantial support for its clinical application and the development of related drugs.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119098"},"PeriodicalIF":4.8000,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2024.119098","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: Yougui Pill (YGP), originating from Jingyue Quanshu, comprises 10 traditional Chinese medicines (TCMs). This classic prescription is renowned for its ability to tonify the kidney, warm the kidney, promote yang, warm the interior, and dispel cold. YGP has proven effective in treating degenerative knee arthritis, osteoporosis, delayed fracture healing, and other orthopedic conditions, making it a widely used clinical prescription for knee osteoarthritis (KOA).
Aim of the study: Although YGP is commonly used in clinical practice, its pharmacodynamic material basis and anti-arthritis mechanisms remain unclear. This study aims to comprehensively analyze the chemical constituents of YGP and elucidate its anti-arthritis mechanisms.
Materials and methods: Ultra-high performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry(ESI-Q TRAP-MS/MS) was used to identify the chemical constituents of YGP. The Hulth method was utilized to establish KOA rat model, and pathological examinations were performed to assess the anti-arthritis effects of YGP. Integrated metabolomics and transcriptomics analyses were conducted to explore the anti-arthritis mechanisms of YGP. Key targets were confirmed via immunohistochemistry.
Results: A total of 1981 chemical components were identified in YGP, predominantly phenolic acids and flavonoids. Compared with the model group, 422 differentially expressed metabolites and 214 differentially expressed genes were identified, primarily involving the MAPK signaling pathway, FoxO signaling pathway, and PI3K-Akt pathway. YGP exerted an anti-osteoarthritis effect by inhibiting the excessive activation of the EGFR/ERT/FOS signaling pathway.
Conclusions: TCM offers significant advantages in the treatment of KOA, addressing the shortcomings of current clinical medications. YGP displayed exceptional pharmacodynamic effects. This study elucidated its pharmacodynamic material basis and anti-osteoarthritis mechanisms, providing substantial support for its clinical application and the development of related drugs.
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.
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