Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways
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ORIGINAL ARTICLE
Andrographolide Benefits Rheumatoid Arthritis via Inhibiting MAPK Pathways Zun-zhong Li,1 Ju-peng Tan,2 Li-li Wang,3 and Qing-hua Li4,5
Abstract— Andrographolide (AD) is the main compound distributed in medicinal herb
Andrographis paniculata and exhibits anti-inflammatory activity. AD has been used for the treatment of multiple inflammatory diseases. However, the therapeutic value of AD on human rheumatoid arthritis (RA) remains unclear. In this study, we investigated the effects of AD on collagen-induced arthritis (CIA) and human RA synovial fibroblasts (RA-SFs). CIA mice were treated with AD (dissolved in 0.5% CMC-Na, 100 mg/kg per day) or vehicle (0.5% CMC-Na) daily by oral gavage for 2 weeks. The arthritis severity and joint destruction were assessed. Serum anti-collagen II antibody (anti-CII Abs) and cytokines were determined by ELISA. TNFα-stimulated human RA-SFs were treated with varying doses of AD for in vitro investigation. Results showed that AD significantly attenuated the arthritis severity and joint damage. AD treatment significantly reduced the production of serum anti-CII, TNFα, IL-1β, and IL-6. In vitro, AD decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RASFs in a dose-dependent manner. AD treatment reduced the TNFα-induced phosphorylation of p38 MAPK and ERK1/2 in a dose-dependent manner. Thus, our findings suggest that AD confers protective effects on autoimmune arthritis through inhibiting MAPK pathways. KEY WORDS: andrographolide; collagen-induced arthritis; rheumatoid arthritis; synovial fibroblasts.
INTRODUCTION Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which can cause cartilage and bone damage as Electronic supplementary material The online version of this article (doi:10.1007/s10753-017-0600-y) contains supplementary material, which is available to authorized users. 1
Department of Rheumatology and Immunology, Linyi People’s Hospital, Linyi, Shandong 276003, China 2 Department of Rheumatology and Immunology, Yidu Central Hospital, Weifang, Shandong 262500, China 3 Clinical Laboratory, Qingzhou Maternal and Child Health Hospital, Weifang, Shandong 262500, China 4 Department of Pediatrics, Women and Children’s Hospital of Linyi City, No.1 Qinghe South Road, Linyi, Shandong 276014, China 5 To whom correspondence should be addressed at Department of Pediatrics, Women and Children’s Hospital of Linyi City, No.1 Qinghe South Road, Linyi, Shandong 276014, China. E-mail: [email protected]
well as disability [1]. Besides infiltration of lymphocytes into synovial tissue, hyperproliferation of synovial fibroblasts (SF) maintains the persistence of inflammation in the joint underpinned by a unique pathological phenotype driven by multiple epigenetic modifications [2]. SF continue to grow in prominence both as the subjects of research into the pathogenesis of RA and as novel therapeutic targets [3]. Andrographis paniculata is a traditional herb that has been used in Taiwan, China, India, and other Southeast Asian countries for treating i
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