Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K/AKT Signaling Pathway
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ORIGINAL ARTICLE
Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K/AKT Signaling Pathway Xiang Li1 and Yue Wang
1,2
Abstract— Cinnamaldehyde (CA), as an active compound isolated from the bark of Cinnamomum cassia, has been reported to possess the anti-fungal, anti-bacterial, antiinflammatory, anti-mutagenic, and anti-oxidant properties. However, the possible effects andunderlyingmechanismsofCAonrheumatoidarthritis(RA)havenotbeenrevealedyet.In the present study, we found that CA obviously improved the type II collagen-induced RA in rats,accompaniedwithdecreasingpro-inflammatoryfactors,proliferationandmetastasis.In addition, CA decreased the expression levels of TNF-α, IL-1β, and IL-6 in RA-FLSs. Besides, CA remarkably inhibited the proliferation, downregulated the EdU-positive cells, and promoted apoptosis of RA-FLSs by CCK-8, EdU and flow cytometry analysis. Moreover, the results of wound healing, transwell migration and invasion assays showed that CA inhibited the migration and invasion of RA-FLSs. Further, western blot experiment showed CA inhibited the activation of PI3K/AKT signaling pathway in RA-FLSs. Finally, 740Y-P, the PI3K/AKT signaling pathway activator, could reverse the effects of CA on the proliferation and metastasis in RA-FLSs. In conclusion, we confirmed that CA exhibited potential therapeutic properties against RA via suppressing proliferation and metastasis of RA-FLSs by blockage of PI3K/AKT signaling pathway. Therefore, our study provides evidence that CA may emerge as a therapeutic option for RA treatment. KEY WORDS: Cinnamaldehyde; Rheumatoid arthritis; Fibroblast-like synoviocytes; PI3K/AKT signaling pathway.
INTRODUCTION Rheumatoid arthritis (RA) is a heterogeneous, systemic, and autoimmune disease characterized by symmetrical arthritis. According to statistics, about 0.5–1.0% of 1
Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China 2 To whom correspondence should be addressed at Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China. E-mail: [email protected]
the global population suffers from RA, and nearly 1/3 of them may be seriously disabled within 20 years [1, 2]. RA can be seen in all age groups, but the main age range is 30– 50 years old, and women are susceptible; the prevalence rate of men and women is about 1: 3 [3]. According to the degree of clinical onset, RA can be divided into occult, subacute, and paroxysmal categories, and there are some differences in the course, severity, prognosis, and outcome of different types [4]. However, the common feature is that RA is the chronic, progressive, and aggressive disease. If RA is not properly treated, it will gradually aggravate and develop, and eventually lead to a considerable disability
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Li, and Wang rate and
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