Suppression of the onset and progression of collagen-induced arthritis by chebulagic acid screened from a natural product library.
OBJECTIVE
Chebulagic acid (CHE) from the immature seeds of Terminalia chebula was identified from a natural product library as a potent suppressor of T cell activity. This study examined the effectiveness of CHE against the onset and progression of collagen-induced arthritis (CIA) in mice.


METHODS
Arthritis was induced in DBA/1J mice by subcutaneous immunization with bovine type II collagen on days 0 and 21. CHE was administered intraperitoneally for 3 weeks, either as prophylaxis (10 or 20 mg/kg) before disease onset or as therapy (20 mg/kg) after disease onset. Clinical scores, serum antibody levels, and cytokines were measured, and flow cytometric analysis and real-time reverse transcription-polymerase chain reaction were performed to evaluate the knee joints of mice with CIA.


RESULTS
In both the prophylactic and therapeutic CHE dosing models, all clinical scores, serum levels of total and anticollagen IgG, and levels of interleukin-10 (IL-10) and IL-6 were reduced, while serum levels of transforming growth factor beta (TGFbeta) were markedly elevated. The number of granulocytes was reduced, but the proportion of CD4+,CD25+ T cells was greater in the knee joints of CHE-treated CIA mice. Expression of Foxp3 and TGFbeta messenger RNA was also augmented significantly in the knee joints of CHE-treated CIA mice in the therapeutic dosing model.


CONCLUSIONS
CHE significantly suppressed the onset and progression of CIA in mice. Immune suppression via the induction of TGFbeta and CD4+,CD25+ T cells may represent a new strategy in the development of therapies for managing rheumatoid arthritis and other inflammatory diseases.
Lee
Sang-Ik
SI
Institute of Traditional Medicine and Bioscience, Daejeon University, Yongun-dong, Dong-gu, Daejeon 300-716, Republic of Korea.
Hyun
Pung-Mi
PM
Kim
Seung-Hyung
SH
Kim
Kyoung-Shin
KS
Lee
Sang-Keun
SK
Kim
Byoung-Soo
BS
Maeng
Pil Jae
PJ
Lim
Jong-Soon
JS
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D003094:Collagen / Q000276:immunology; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D019169:Jurkat Cells; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059004:Topoisomerase I Inhibitors
D001578:Benzopyrans; D001688:Biological Products; D016207:Cytokines; D005960:Glucosides; D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D059004:Topoisomerase I Inhibitors; C076178:chebulagic acid; D003094:Collagen