Abstract
Previous studies have shown that the natural diterpene compound, sclareol, potentially inhibits inflammation, but it has not yet been determined whether sclareol can alleviate inflammation associated with rheumatoid arthritis (RA). Here, we utilized human synovial cell line, SW982, and an experimental murine model of rheumatoid arthritis, collagen-induced arthritis (CIA), to evaluate the therapeutic effects of sclareol in RA. Arthritic DBA/1J mice were dosed with 5 and 10 mg/kg sclareol intraperitoneally every other day over 21 days. Arthritic severity was evaluated by levels of anti-collagen II (anti-CII) antibody, inflammatory cytokines, and histopathologic examination of knee joint tissues. Our results reveal that the serum anti-CII antibody, cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-17, as well as Th17 and Th1 cell population in inguinal lymph nodes, were significantly lower in sclareol-treated mice compared to the control group. Also, the sclareol treatment groups showed reduced swelling in the paws and lower histological arthritic scores, indicating that sclareol potentially mitigates collagen-induced arthritis. Furthermore, IL-1β-stimulated SW982 cells secreted less inflammatory cytokines (TNF-α and IL-6), which is associated with the downregulation of p38-mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-κB pathways. Overall, we demonstrate that sclareol could relieve arthritic severities by modulating excessive inflammation and our study merits the pharmaceutical development of sclareol as a therapeutic treatment for inflammation associated with RA.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia, chronic joint inflammation, and bone destruction, where fibroblast-like synoviocytes (FLS) appear to play a vital role in the in the pathogenesis of destructive arthritis [1]
We first confirmed that the arthritic scores in collagen-induced arthritis (CIA) mice were significantly increased compared to that of the non-immunized mice throughout the experiment (Figure 1A)
To elucidate whether Th17/Th17 and regulatory (Treg) and Th1 are associated with the sclareol-mediated anti-arthritic activity, we examined the frequency of Th17, Th1, and Treg cells in draining inguinal lymph nodes (ILNs) using flow cytometry
Summary
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia, chronic joint inflammation, and bone destruction, where fibroblast-like synoviocytes (FLS) appear to play a vital role in the in the pathogenesis of destructive arthritis [1]. Sclareol (labd-14-ene-8, 13-diol) is a member of bioactive labdane-type diterpenes, extracted from the leaves and flowers of Clary sage (Salvia sclarea L.) of the Lamiaceae family, one commonly cultivated for its essential oil that has been widely used as raw material for food, cosmetic products, and folk medicine. Several studies, both in vitro and in vivo, have shown that sclareol possesses immuno-modulation activities. Sclareol exerts anti-osteoarthritic activities by regulating the balance between MMPs and TIMPs (tissue inhibitors of metalloproteinases) as well as inhibiting iNOS and COX-2 expression in interleukin-1β-induced rabbit chondrocytes and an experimental rabbit knee osteoarthritis model [13]
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