Abstract

BackgroundThe root of Angelica sinensis (AS), also known as “Dang-gui,” was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. This study aimed to determine the effects of ethyl acetate fraction from Angelica sinensis (EAAS) on the interleukin-1β (IL-1β)-induced proliferation of rheumatoid arthritis synovial fibroblasts (RASFs), and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) 2, and prostaglandin E2 (PGE2), involved in articular bone and cartilage destruction, by RASFs.ResultsRASF proliferation was evaluated with cholecystokinin octapeptide (CCK-8) reagent in the presence of IL-1β with/without EAAS. Expression of MMPs, tissue inhibitor of metalloproteinases-1 (TIMP-1), COXs, PGE2, and intracellular mitogen-activated protein kinase (MAPK) signaling molecules, including p-ERK, p-p38, p-JNK, and NF-κB, were examined using immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. EAAS inhibited IL-1β-induced RASF proliferation; MMP-1, MMP-3, and COX-2 mRNA and protein expressions; and PGE2 production. EAAS also inhibits the phosphorylation of ERK-1/2, p38, and JNK, and activation of NF-κB by IL-1β.ConclusionEAAS might be a new therapeutic modality for rheumatoid arthritis management.

Highlights

  • The root of Angelica sinensis (AS), known as “Dang-gui,” was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time

  • ethyl acetate fraction from Angelica sinensis (EAAS) inhibits IL-1β-induced prostaglandin E2 (PGE2) production in rheumatoid arthritis synovial fibroblasts (RASFs) To confirm the effect of EAAS on the role of IL-1β in PGE2 production by RASFs, we examined the concentration of PGE2 in the culture supernatant

  • Further investigation is needed to discern how EAAS suppresses nuclear factor κB (NF-κB) activation, and to identify the components of NF-κB that are suppressed and the kind of intracellular signaling factors or directly involved in the effect of EAAS on the proliferation and PGE2 production in RASFs. This is the first study to report that EAAS can inhibit the IL-1β-induced proliferation of RASFs, expression of COX-2, and production of PGE2

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Summary

Introduction

The root of Angelica sinensis (AS), known as “Dang-gui,” was a popular herbal medicine widely used in the treatment of gynecological diseases in China, Korea, and Japan for a long time. Synovial fibroblasts mediate joint destruction in RA by producing inflammatory mediators such as cytokines, matrix metalloproteinases (MMPs), and cyclooxygenase (COX)-2 that facilitate the expansion and invasion of synovial fibroblasts into the adjacent tissue. Chemical and pharmacological studies of various extracts or compounds obtained from this herb were found to increase myocardial blood flow, reduce radiation damages [4,5,6] It was demonstrated as mainly consisting of polysaccharides and having a protective effect on gastrointestinal damage and hepatic injury [7,8]. No study has investigated the effects of EAAS on inflammatory reactions, including proliferation of RASFs and production of PGE2 by RASFs, which play a crucial role in the pathogenesis of synovitis in RA

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