Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways
Abstract Background Osteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-025-05525-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861837916012544 |
|---|---|
| author | Liang Zhu Yanchi Bi Ting Liang Po Zhang Xiao Xiao Tengbo Yu |
| author_facet | Liang Zhu Yanchi Bi Ting Liang Po Zhang Xiao Xiao Tengbo Yu |
| author_sort | Liang Zhu |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic chemical, has proven anti-inflammatory, antioxidant, anti-tumor, and neuroprotective effects. Methods First, this study utilizes network pharmacology to explore the intrinsic connection between GK and OA. In vitro, SW1353 human cartilage cells were stimulated with Tert-butyl hydrogen peroxide (TBHP), and different GK concentrations were pre-treated to evaluate its protective effects. GK's anti-inflammatory and antioxidative effects were comprehensively assessed via MTT assay, western blot, cell immunofluorescence, ELISA, and transcriptome sequencing. Potential underlying mechanisms were also explored. In vivo, OA was induced in rats via anterior cruciate ligament transection (ACLT), and GK's impact on cartilage protection was further assessed via histological analysis and western blot. Results Network pharmacology has revealed that GK regulates OA via several key pathways, especially NF-κB, HIF-1, PI3K-AKT, and substances like reactive oxygen species. In vitro experiments showed GK effectively reverses oxidative stress damage from TBHP, inhibits inflammatory factor release, and protects Extracellular matrix (ECM) from degradation. These functions may be achieved via the NF-κB and MAPK signaling pathways. In vivo experiments showed GK significantly reduced proteoglycan loss from ACLT and inhibited matrix metalloproteinase 13 (MMP13) and ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) production, effectively preventing cartilage degeneration in rats. Conclusion These findings suggest that GK has potential as a therapeutic agent for OA, offering new strategies and directions for OA treatment. |
| format | Article |
| id | doaj-art-b72189cbc4f94eae9450610fed9e44ca |
| institution | Kabale University |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-b72189cbc4f94eae9450610fed9e44ca2025-02-09T12:46:59ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-02-0120112010.1186/s13018-025-05525-5Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathwaysLiang Zhu0Yanchi Bi1Ting Liang2Po Zhang3Xiao Xiao4Tengbo Yu5Department of Orthopedic Surgery, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Orthopedic Surgery, Qingdao Municipal Hospital, Qingdao UniversityRehabilitation Section, Qingdao Municipal Hospital, Qingdao UniversityDepartment of Orthopedic Surgery, Qingdao Municipal Hospital, Qingdao UniversityCentral Laboratories, Qingdao Municipal Hospital, University of Health and Rehabilitation SciencesDepartment of Orthopedic Surgery, Qingdao Municipal Hospital, University of Health and Rehabilitation SciencesAbstract Background Osteoarthritis (OA) is considered an advancing chronic degenerative joint disease, leading to severe physical functional impairment of patients. Its development is closely related to increased inflammation and oxidative stress within the joint. Ginkgetin (GK), a natural non-toxic chemical, has proven anti-inflammatory, antioxidant, anti-tumor, and neuroprotective effects. Methods First, this study utilizes network pharmacology to explore the intrinsic connection between GK and OA. In vitro, SW1353 human cartilage cells were stimulated with Tert-butyl hydrogen peroxide (TBHP), and different GK concentrations were pre-treated to evaluate its protective effects. GK's anti-inflammatory and antioxidative effects were comprehensively assessed via MTT assay, western blot, cell immunofluorescence, ELISA, and transcriptome sequencing. Potential underlying mechanisms were also explored. In vivo, OA was induced in rats via anterior cruciate ligament transection (ACLT), and GK's impact on cartilage protection was further assessed via histological analysis and western blot. Results Network pharmacology has revealed that GK regulates OA via several key pathways, especially NF-κB, HIF-1, PI3K-AKT, and substances like reactive oxygen species. In vitro experiments showed GK effectively reverses oxidative stress damage from TBHP, inhibits inflammatory factor release, and protects Extracellular matrix (ECM) from degradation. These functions may be achieved via the NF-κB and MAPK signaling pathways. In vivo experiments showed GK significantly reduced proteoglycan loss from ACLT and inhibited matrix metalloproteinase 13 (MMP13) and ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) production, effectively preventing cartilage degeneration in rats. Conclusion These findings suggest that GK has potential as a therapeutic agent for OA, offering new strategies and directions for OA treatment.https://doi.org/10.1186/s13018-025-05525-5GinkgetinOsteoarthritisNetwork pharmacologyOxidative stress |
| spellingShingle | Liang Zhu Yanchi Bi Ting Liang Po Zhang Xiao Xiao Tengbo Yu Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways Journal of Orthopaedic Surgery and Research Ginkgetin Osteoarthritis Network pharmacology Oxidative stress |
| title | Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways |
| title_full | Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways |
| title_fullStr | Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways |
| title_full_unstemmed | Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways |
| title_short | Ginkgetin delays the progression of osteoarthritis by inhibiting the NF-κB and MAPK signaling pathways |
| title_sort | ginkgetin delays the progression of osteoarthritis by inhibiting the nf κb and mapk signaling pathways |
| topic | Ginkgetin Osteoarthritis Network pharmacology Oxidative stress |
| url | https://doi.org/10.1186/s13018-025-05525-5 |
| work_keys_str_mv | AT liangzhu ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways AT yanchibi ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways AT tingliang ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways AT pozhang ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways AT xiaoxiao ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways AT tengboyu ginkgetindelaystheprogressionofosteoarthritisbyinhibitingthenfkbandmapksignalingpathways |