Kirenol exerts a potent anti-arthritic effect in collagen-induced arthritis by modifying the T cells balance

• Published in: Phytomedicine (Stuttgart) Vol. 19; no. 10; pp. 882 - 889
• Main Authors: Lu, Yue, Xiao, Juan, Wu, Zai-Wang, Wang, Zhe-Ming, Hu, Jia, Fu, Hong-Zheng, Chen, Ying-Yu, Qian, Rui-Qin
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15.07.2012; Urban & Fischer Verlag
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antiarthritic agents; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Experimental - drug therapy; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Asteraceae - chemistry; Bone and Bones - drug effects; Bone and Bones - pathology; Cartilage - drug effects; Cartilage - pathology; Cattle; CD4-Positive T-Lymphocytes - metabolism; Cell Proliferation - drug effects; Collagen Type II; Collagen-induced arthritis; Cytokines - blood; Diterpenes - pharmacology; Diterpenes - therapeutic use; Drug therapy; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Health aspects; Herba Siegesbeckiae; Immunosuppression; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Inflammation - drug therapy; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - metabolism; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukins; Joint Diseases - drug therapy; Joint Diseases - immunology; Joint Diseases - metabolism; Kirenol; Leukocytes, Mononuclear - metabolism; Lymph Nodes - cytology; Lymph Nodes - drug effects; Physiological aspects; Phytotherapy; Prednisolone - pharmacology; Prednisolone - therapeutic use; Rats; Rats, Wistar; Rheumatoid arthritis; RNA, Messenger - metabolism; Severity of Illness Index; Spleen - cytology; Spleen - drug effects; Synovial Fluid - drug effects; Synovial Fluid - metabolism; T cell; T cells; T-Lymphocytes, Regulatory - metabolism; China; Herba Siegesbeckiae; Immunosuppression; Kirenol; Rheumatoid arthritis; Collagen-induced arthritis; T cell
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2012.04.010

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), 2mg/kg Kirenol or 2mg/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.