Ethyl Acetate Extract from Celastrus aculeatus Merr. Suppresses Synovial Inflammation in Adjuvant Arthritis Rats through Apoptosis Induction of CD4(+)CD25(+)FOXP3(+) T Cells.

Shu-Tong Bai,Yu-Yao Chen,Xiao-Chun Lin,Pei-Hong Chen,Jun-Shan Liu,Li Tong

doi:10.1155/2014/460136

Abstract

Celastrus aculeatus Merr. has been widely used in traditional Chinese medicine to treat rheumatoid arthritis (RA) in clinic. However, the main active fraction of this plant is still unclear. In this study, we attempted to evaluate the suppressive effect of ethyl acetate extract (EAE) from Celastrus aculeatus Merr. on synovial inflammation in adjuvant arthritis (AA) rats induced by Mycobacterium tuberculosis H37Ra (Mtb) and to explore the underlying mechanisms. SD rats immunized with heat-killed Mtb were fed with EAE and observed for erythema, swelling, and induration of each paw. The pathologic changes in joint synovium were tested by hematoxylin-eosin staining. Apoptosis induction of synoviocytes was tested immunohistochemically. Apoptosis of peripheral lymphocytes and the level of regulatory T cells were analyzed by flow cytometry. After treatment with EAE, the joint inflammation in rats with AA was alleviated. Both apoptotic ratios of synoviocytes and peripheral lymphocytes and the ratio of CD4+CD25+FOXP3+ to CD4 regulatory T cells were significantly increased. In summary, we first demonstrated that EAE of Celastrus aculeatus Merr. can inhibit synovial inflammation in AA rats through apoptosis induction of CD4+CD25+FOXP3+ T cells. Our study provides a rationale for the application of Celastrus aculeatus Merr. to treat RA.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the inflammatory proliferation of synovial tissues and progressive destruction of articular cartilage
We demonstrated that the ethanol extract of Celastrus aculeatus Merr. has significant anti-inflammatory and analgesic effects in animal models [9,10,11,12] and suppresses the induction and progression of adjuvant arthritis (AA)
Lymphocyte (LY), monocyte (MO), and red blood cell (RBC) count did not change obviously, while the abnormality in blood hemogram was relived after ethyl acetate extract (EAE) injection

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the inflammatory proliferation of synovial tissues and progressive destruction of articular cartilage. It was reported that the accumulation of inflammatory cells, proliferation of synovial tissue, and bone destruction in joints are related to immune network imbalance [1, 2]. The CD4+CD25+ T cells show immune regulatory functions both in vitro and in vivo, as they can inhibit the autoimmune diseases and may participate in the induction of transplantation tolerance. CD4+CD25+ T cells play an important role in maintaining the stability of the internal environment [4], while the decrease or dysfunction of Treg may result in autoimmune diseases. We demonstrated that the ethanol extract of Celastrus aculeatus Merr. We demonstrated that the ethanol extract of Celastrus aculeatus Merr. has significant anti-inflammatory and analgesic effects in animal models [9,10,11,12] and suppresses the induction and progression of adjuvant arthritis (AA)

Methods

Results

Conclusion