Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance.
Rheumatoid arthritis is characterized by the imbalance of T cells, which leads to increased pro-inflammatory and reduced anti-inflammatory cytokines. Modulating the balance among T cells is crucial for the treatment of RA. Kirenol is a major diterpenoid components of Herba Siegesbeckiae, which has been applied for arthritic therapy for centuries. Since prior research showed Kirenol exhibited anti-inflammatory effect in rats, in this study we have evaluated the effect and mechanism of bioactive Kirenol in a rat model of collagen-induced arthritis (CIA) on modulation of T cells. After immunization with bovine type II collagen (CII), Wistar rats were orally administered saline (CIA group), 2 mg/kg Kirenol or 2 mg/kg prednisolone daily for 30 days. The severity of arthritis was clinically and histologically assessed. The numbers of CD4⁺CD25⁺Foxp3⁺ T regulatory cells (Tregs) and IFNγ⁺CD4⁺ and IL4⁺CD4⁺ T cells were determined by flow cytometry, the mRNA expression level of Foxp3 was quantified by RT-PCR, cytokine levels were measured by ELISA and CII-induced cell proliferation was quantified in vitro. Kirenol significantly delayed the occurrence and reduced the disease severity of CIA. Histological analysis confirmed Kirenol suppressed joint inflammation and inhibited cartilage and bone destruction, compared to the CIA group. Kirenol also upregulated the mRNA expression of Foxp3, increased the numbers of CD4⁺CD25⁺Foxp3⁺ and IL4⁺CD4⁺ T cells, and reduced the number of IFNγ⁺CD4⁺ T cells. Kirenol reduced the levels of TNF-α, IL-17A and IL-6 in synovial fluid and TNF-α, IL-17A and IFN-γ in serum, and increased the serum levels of IL-4, IL-10 and TGF-β1. In addition, Kirenol inhibited the ability of CII to induce splenocyte, PBMC and lymph node cell proliferation in vitro, compared to cells from CIA rats. In conclusion, these results suggest that Kirenol may be a potential immunosuppressant for the treatment for rheumatoid arthritis.
Department of Integrated Chinese Traditional with Western Medicine, Peking University Health Science Center, Beijing 100191, China.
Yue
Y
Lu
Juan
J
Xiao
Zai-Wang
ZW
Wu
Zhe-Ming
ZM
Wang
Jia
J
Hu
Hong-Zheng
HZ
Fu
Ying-Yu
YY
Chen
Rui-Qin
RQ
Qian
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D019659:Asteraceae / Q000737:chemistry*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II; D016207:Cytokines / Q000097:blood*; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007592:Joint Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008517:Phytotherapy; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D024043:Collagen Type II; D016207:Cytokines; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; C560087:kirenol; D011239:Prednisolone