PMID- 33313242
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 8
IP  - 22
DP  - 2020 Nov
TI  - Ginkgolide B attenuates collagen-induced rheumatoid arthritis and regulates 
      fibroblast-like synoviocytes-mediated apoptosis and inflammation.
PG  - 1497
LID - 10.21037/atm-20-6420 [doi]
LID - 1497
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic disease characterized by 
      chronic synovial infiltration and proliferation, cartilage destruction, and joint 
      injury. Ginkgolide B (GB) is an extract of the leaves of Ginkgo biloba, and 
      pharmacological studies have shown that it has anti-inflammatory and 
      anti-apoptotic activities. The purpose of this study was to investigate the 
      anti-RA properties of GB. METHODS: In vivo, we established a collagen II-induced 
      arthritis (CIA) mouse model. Mice were divided into five groups (n=10): sham, 
      CIA, GB (10 microM), GB (20 microM), and GB (40 microM). We measured arthritis score, 
      synovial histopathological change, and peripheral blood cytokine levels. In 
      vitro, we used lipopolysaccharide (LPS)-induced-fibroblast-like synoviocytes 
      (RA-FLSs) as the study subject. Cell viability, apoptosis, and inflammatory 
      cytokines levels were detected by 3-(4,5)-dimethylthiahiazo 
      (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flow cytometry, and 
      quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), 
      respectively. Finally, the protein expression of wingless-type family member 5A 
      (Wnt5a), c-Jun N-terminal kinase (JNK), and nuclear factor 
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) p65 were detected by 
      Western blot. RESULTS: Arthritis scores, synovial hyperplasia, and cartilage and 
      bone destruction were significantly ameliorated by GB. Additionally, GB decreased 
      the serum levels of interleukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1 
      (MCP-1), and tumor necrosis factor alpha (TNF-alpha), matrix metalloproteinase 
      (MMP)-3 and MMP-13, and increased IL-10. In vitro, we found that GB remarkably 
      inhibited RA-FLSs viability at 24 or 48 h in a concentration-dependent manner. 
      The apoptotic ratio was reduced by GB, and it increased the expression of 
      cleaved-Caspase-3 and Bax while decreasing Bcl-2 expression in RA-FLSs. 
      Furthermore, GB attenuated the progression of inflammation by mediating 
      inflammatory cytokine release and MMPs gene expression. Meanwhile, GB inactivated 
      the expression levels of Wnt5a, phosphorylated (p)-JNK, and p-P65 in the synovial 
      tissues and RA-FLSs. CONCLUSIONS: This study was the first to demonstrate that 
      the anti-RA effect of GB is related to reducing articular cartilage and bone 
      destruction, inducing RA-FLSs apoptosis, and regulating inflammatory cytokine 
      release and the Wnt5a/JNK/NF-kappaB axis. All the findings highlight that GB might 
      provide a novel treatment approach for RA.
CI  - 2020 Annals of Translational Medicine. All rights reserved.
FAU - Xie, Chuanmei
AU  - Xie C
AD  - Department of Rheumatology, the Affiliated Hospital of North Sichuan Medical 
      College, Nanchong, China.
FAU - Jiang, Jing
AU  - Jiang J
AD  - Department of Gynecology and Obstetrics, the Affiliated Hospital of North Sichuan 
      Medical College, Nanchong, China.
FAU - Liu, Jianping
AU  - Liu J
AD  - Department of Rheumatology, the Affiliated Hospital of North Sichuan Medical 
      College, Nanchong, China.
FAU - Yuan, Guohua
AU  - Yuan G
AD  - Department of Rheumatology, the Affiliated Hospital of North Sichuan Medical 
      College, Nanchong, China.
FAU - Zhao, Zhenyi
AU  - Zhao Z
AD  - Department of Rheumatology, the Affiliated Hospital of North Sichuan Medical 
      College, Nanchong, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC7729381
OTO - NOTNLM
OT  - Ginkgolide B (GB)
OT  - fibroblast-like synoviocytes (FLSs)
OT  - inflammation
OT  - rheumatoid arthritis (RA)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-20-6420). The authors have no 
      conflicts of interest to declare.
EDAT- 2020/12/15 06:00
MHDA- 2020/12/15 06:01
PMCR- 2020/11/01
CRDT- 2020/12/14 11:00
PHST- 2020/12/14 11:00 [entrez]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2020/12/15 06:01 [medline]
PHST- 2020/11/01 00:00 [pmc-release]
AID - atm-08-22-1497 [pii]
AID - 10.21037/atm-20-6420 [doi]
PST - ppublish
SO  - Ann Transl Med. 2020 Nov;8(22):1497. doi: 10.21037/atm-20-6420.