Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Zuxiang Chen
- Li Zhou
- Yanzhi Ge
- Junjie Chen
- Wenxi Du
- Luwei Xiao
- Peijian Tong
- Jiefeng Huang
- Letian Shan
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000794990600002&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2022.154071
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1F2GH
- PubMed Identifier: 35378415
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Fuzi decoction
- Osteoarthritis
- PI3K
- Akt
- Chondrocyte
- Artikelnummer
- ARTN 154071
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence
- Sub types
- Article
- Ausgabe der Zeitschrift
- 100
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Zuxiang Chen
- Li Zhou
- Yanzhi Ge
- Junjie Chen
- Wenxi Du
- Luwei Xiao
- Peijian Tong
- Jiefeng Huang
- Letian Shan
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2022.154071
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 154071
- Paginierung
- 154071 - 154071
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2022.154071
- Datum der Datenerfassung
- 2023
- Titel
- Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence
- Ausgabe der Zeitschrift
- 100
Data source: Crossref
- Abstract
- <h4>Background</h4>Osteoarthritis (OA) is a difficult disease but the clinic lacks effective therapy. As a classic formula of traditional Chinese medicine (TCM), Fuzi decoction (FZD) has been clinically applied for treating OA-related syndromes, but its anti-OA efficacy and mechanism remain unclear.<h4>Purpose</h4>To experimentally and clinically determine the anti-OA efficacy of FZD and clarify the underlying mechanism.<h4>Methods</h4>UPLC/MS/MS was applied to identify the main components of FZD. A monoiodoacetate (MIA)-induced OA rat model was employed to evaluate the in vivo efficacy of FZD against OA, by using pain behavior assessment, histopathological observation, and immunohistochemical analysis. Primary rat chondrocytes were isolated to determine the in vitro effects of FZD by using cell viability assay, wound healing assay, and real-time PCR (qPCR) analysis on anabolic/catabolic mRNA expressions. RNA sequencing (RNA-seq) and network pharmacology analysis were conducted and the overlapping data were used to predict the mechanism of FZD, followed by verification with qPCR and Western blot assays. Finally, a retrospective analysis was performed to confirm FZD's efficacy and safety in OA patients.<h4>Results</h4>The UPLC/MS/MS result showed that FZD contained atractylenolide I, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, hypaconitine, mesaconitine, aconitine, lobetyolin, paeoniflorin, and pachymic acid. The in vivo data showed that FZD restored the cartilage degeneration in MIA-induced OA rats by ameliorating pain behavior parameters, recovering histopathological alterations, benefitting cartilage anabolism (up-regulating Col2 expression), and suppressing catabolism (down-regulating MMP13 and Col10 expressions). The in vitro data showed that FZD increased cell viability and wound healing capacity of chondrocytes, and restored the altered expressions of anabolic and catabolic genes of chondrocytes. The overlapping results of RNA-seq and network pharmacology analysis suggested that PI3K/Akt signaling mediated the anti-OA mechanism of FZD, which was verified by qPCR and Western blot experiments. Clinically, the anti-OA efficacy and safety of FZD were confirmed by the retrospective analysis on OA patients.<h4>Conclusion</h4>The scientific innovation of this study was the determination of anti-OA efficacy of FZD by experimental and clinical evidence and the discovery of its mechanism by integrated RNA-seq, network pharmacology, and molecular experiments, which suggests FZD as a promising TCM agency for OA treatment.
- Addresses
- The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.
- Autoren
- Zuxiang Chen
- Li Zhou
- Yanzhi Ge
- Junjie Chen
- Wenxi Du
- Luwei Xiao
- Peijian Tong
- Jiefeng Huang
- Letian Shan
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2022.154071
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 35378415
- Funding acknowledgements
- National Natural Science Foundation of China:
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cartilage
- Cartilage, Articular
- Animals
- Humans
- Rats
- Rats, Sprague-Dawley
- Osteoarthritis
- Pain
- Diterpenes
- Drugs, Chinese Herbal
- Retrospective Studies
- Signal Transduction
- Proto-Oncogene Proteins c-akt
- Tandem Mass Spectrometry
- Phosphatidylinositol 3-Kinases
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Paginierung
- 154071
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 100
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: Osteoarthritis (OA) is a difficult disease but the clinic lacks effective therapy. As a classic formula of traditional Chinese medicine (TCM), Fuzi decoction (FZD) has been clinically applied for treating OA-related syndromes, but its anti-OA efficacy and mechanism remain unclear. PURPOSE: To experimentally and clinically determine the anti-OA efficacy of FZD and clarify the underlying mechanism. METHODS: UPLC/MS/MS was applied to identify the main components of FZD. A monoiodoacetate (MIA)-induced OA rat model was employed to evaluate the in vivo efficacy of FZD against OA, by using pain behavior assessment, histopathological observation, and immunohistochemical analysis. Primary rat chondrocytes were isolated to determine the in vitro effects of FZD by using cell viability assay, wound healing assay, and real-time PCR (qPCR) analysis on anabolic/catabolic mRNA expressions. RNA sequencing (RNA-seq) and network pharmacology analysis were conducted and the overlapping data were used to predict the mechanism of FZD, followed by verification with qPCR and Western blot assays. Finally, a retrospective analysis was performed to confirm FZD's efficacy and safety in OA patients. RESULTS: The UPLC/MS/MS result showed that FZD contained atractylenolide I, benzoylhypaconitine, benzoylmesaconitine, benzoylaconitine, hypaconitine, mesaconitine, aconitine, lobetyolin, paeoniflorin, and pachymic acid. The in vivo data showed that FZD restored the cartilage degeneration in MIA-induced OA rats by ameliorating pain behavior parameters, recovering histopathological alterations, benefitting cartilage anabolism (up-regulating Col2 expression), and suppressing catabolism (down-regulating MMP13 and Col10 expressions). The in vitro data showed that FZD increased cell viability and wound healing capacity of chondrocytes, and restored the altered expressions of anabolic and catabolic genes of chondrocytes. The overlapping results of RNA-seq and network pharmacology analysis suggested that PI3K/Akt signaling mediated the anti-OA mechanism of FZD, which was verified by qPCR and Western blot experiments. Clinically, the anti-OA efficacy and safety of FZD were confirmed by the retrospective analysis on OA patients. CONCLUSION: The scientific innovation of this study was the determination of anti-OA efficacy of FZD by experimental and clinical evidence and the discovery of its mechanism by integrated RNA-seq, network pharmacology, and molecular experiments, which suggests FZD as a promising TCM agency for OA treatment.
- Date of acceptance
- 2022
- Autoren
- Zuxiang Chen
- Li Zhou
- Yanzhi Ge
- Junjie Chen
- Wenxi Du
- Luwei Xiao
- Peijian Tong
- Jiefeng Huang
- Letian Shan
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35378415
- DOI
- 10.1016/j.phymed.2022.154071
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Chondrocyte
- Fuzi decoction
- Osteoarthritis
- PI3K/Akt
- Animals
- Cartilage
- Cartilage, Articular
- Diterpenes
- Drugs, Chinese Herbal
- Humans
- Osteoarthritis
- Pain
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- Rats
- Rats, Sprague-Dawley
- Retrospective Studies
- Signal Transduction
- Tandem Mass Spectrometry
- Sprache
- eng
- Country
- Germany
- Paginierung
- 154071
- PII
- S0944-7113(22)00149-0
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Fuzi decoction ameliorates pain and cartilage degeneration of osteoarthritic rats through PI3K-Akt signaling pathway and its clinical retrospective evidence.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 100
Data source: PubMed
- Beziehungen:
- Property of