Abstract
Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Fibroblast-like synoviocytes (FLS) play a pathogenic role in RA. Activation of signal transducer and activator of transcription 3 (STAT3) promotes proliferation and suppresses apoptosis of RA-FLS, resulting in synovial hyperplasia and joint damage. Chrysoeriol (CSR), a flavone found in diverse medicinal herbs, has been shown to have anti-inflammatory effects and inhibit STAT3 signaling.
Objective: This study aimed to determine whether CSR has anti-RA effects, and to investigate the involvement of STAT3 signaling in its effects. Methods: The collagen-induced arthritis (CIA) DBA-1J mouse model was used to assess the in
vivo anti-RA effects of CSR. IL-6/soluble IL-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS were used to evaluate the in vitro effects of CSR.
Results: In animal assays, we found that intragastric administration of CSR attenuated paw swelling and bone erosion, suppressed synovial hyperplasia, down-regulated serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17), and improved body weight gain of CIA mice. We also found that CSR treatments down-regulated Th17 cell proportion, and up-regulated Treg cell proportion in splenocytes of CIA mice. The immunological imbalance of CIA mice,
characterized by a high Th17/Treg ratio, was markedly decreased by CSR treatments. In cell assays, CSR suppressed hyperproliferation of, and evoked apoptosis in, IL-6/sIL-6R-stimulated RA-FLS. Mechanistic studies revealed that CSR inhibited activation/phosphorylation of STAT3 (Tyr705) in synovial tissues of CIA mice and in IL-6/sIL-6R-stimulated RA-FLS. CRS also decreased STAT3 nuclear level and down-regulated protein levels of cleaved caspase-3, cleaved
caspase-9, Bcl-2 and Mcl-1 in the cell model. Over-activation of STAT3 significantly diminished CSR’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS.
Conclusions: We for the first time demonstrated that CSR ameliorates CIA in mice and suppresses hyperproliferation of RA-FLS. Inhibition of STAT3 signaling is involved in CSR’s anti-RA effects. This study provides a pharmacological basis for developing CSR into a novel anti-RA agent.
Objective: This study aimed to determine whether CSR has anti-RA effects, and to investigate the involvement of STAT3 signaling in its effects. Methods: The collagen-induced arthritis (CIA) DBA-1J mouse model was used to assess the in
vivo anti-RA effects of CSR. IL-6/soluble IL-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS were used to evaluate the in vitro effects of CSR.
Results: In animal assays, we found that intragastric administration of CSR attenuated paw swelling and bone erosion, suppressed synovial hyperplasia, down-regulated serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17), and improved body weight gain of CIA mice. We also found that CSR treatments down-regulated Th17 cell proportion, and up-regulated Treg cell proportion in splenocytes of CIA mice. The immunological imbalance of CIA mice,
characterized by a high Th17/Treg ratio, was markedly decreased by CSR treatments. In cell assays, CSR suppressed hyperproliferation of, and evoked apoptosis in, IL-6/sIL-6R-stimulated RA-FLS. Mechanistic studies revealed that CSR inhibited activation/phosphorylation of STAT3 (Tyr705) in synovial tissues of CIA mice and in IL-6/sIL-6R-stimulated RA-FLS. CRS also decreased STAT3 nuclear level and down-regulated protein levels of cleaved caspase-3, cleaved
caspase-9, Bcl-2 and Mcl-1 in the cell model. Over-activation of STAT3 significantly diminished CSR’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS.
Conclusions: We for the first time demonstrated that CSR ameliorates CIA in mice and suppresses hyperproliferation of RA-FLS. Inhibition of STAT3 signaling is involved in CSR’s anti-RA effects. This study provides a pharmacological basis for developing CSR into a novel anti-RA agent.
| Original language | English |
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| Pages | 112-113 |
| Number of pages | 2 |
| Publication status | Published - 22 Jun 2023 |
| Event | The 9th Annual Meeting of The Specialty Committee on Immunology of Traditional Chinese Medicine of the World Federation of Chinese Medicine Societies cum The 6th International Forum on Triplet Therapy for Rheumatism and Pain = 世界中医药学会联合会中医药免疫专业委员会第九届学术年会暨第六届国际风湿与疼痛三联序贯疗法高峰论坛, 2023 - Guiyang, China Duration: 22 Jun 2023 → 24 Jun 2023 |
Conference
| Conference | The 9th Annual Meeting of The Specialty Committee on Immunology of Traditional Chinese Medicine of the World Federation of Chinese Medicine Societies cum The 6th International Forum on Triplet Therapy for Rheumatism and Pain = 世界中医药学会联合会中医药免疫专业委员会第九届学术年会暨第六届国际风湿与疼痛三联序贯疗法高峰论坛, 2023 |
|---|---|
| Country/Territory | China |
| City | Guiyang |
| Period | 22/06/23 → 24/06/23 |