Therapeutic Potential of Sclareol in Experimental Models of Rheumatoid Arthritis

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.

Terpenoids in the Essential Oil and Concentrated Aromatic Products Obtained from Nicotiana glutinosa L. Leaves

“…We also analyzed the activity of the individual component common to the three aromatic products, sclareol, a substance of importance to the fragrance industry. As stated earlier, sclareol was a characteristic component of N. glutinosa leaf derived aromatic products, and data about its antimicrobial and insecticidal activity have been documented previously [9,11,29,58]. Regrettably, the products showed very limited activity against the test-microorganisms in this study.…”

“…The waxy, musky-sweet-earthy-odored ambergris is highly appreciated and widely used as a fixative in fine perfumery, but its original supply depends on an endangered and protected animal species, sperm whales, and therefore investigations on alternative supply routes are relevant. Beside its perfume-fixating value, sclareol is also identified with a number of beneficial activities, such as antifungal, antimicrobial, growth-regulating, anti-inflammatory, and others [9,11,29,58]. Therefore, the results about the high content of sclareol in the two concentrated aromatic products of N. glutinosa, and in particular in the concrete, may be considered very promising in terms of potential future use and larger-scale production.…”

Essential Oils and Bioactive Components against Arthritis: A Novel Perspective on Their Therapeutic Potential

“…Tsai and coworkers assessed the potential therapeutic effects of sclareol on RA using the human synovial cell line SW982 and the collagen-induced arthritis (CIA) mouse model [ 63 ]. The authors demonstrated that this compound can reduce the IL-1β-induced expression of TNF-α, MMP-1, and IL-6 in the SW982 cell line via attenuating NF-κB translocation and the phosphorylation of MAPK pathways.…”

Protective effects of Zhuifeng tougu on collagen-induced arthritis in DBA/1 mice

“…On day 42-49, the synovial tissues of knee joints were extracted. Protein expressions of Bcl-2, Fas, and p53 were determined by Western blot (Sai Bao Biotechnology, Shanghai) as described previously [9].…”