Cinnamaldehyde inhibits inflammation of human synoviocyte cells through regulation of Jak/Stat pathway and ameliorates collagen-induced arthritis in rats.

Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine (TCM) herb Cinnamomum cassia, has been reported to have multi-pharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell cytotoxicity was measured by CCK-8 Assay. Pro-inflammatory cytokine expression was evaluated using qPCR and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg/day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histological examinations. Cin significantly inhibited IL-1β-induced interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6-induced janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1) and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1 and STAT3, without affecting NF-κB pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion and destruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1β-induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential TCM-derived disease modifying anti-rheumatic herbal drug. SIGNIFICANCE STATEMENT: Cin suppresses pro-inflammatory cytokines secretion in RA synoviocyte cells by JAK/STAT pathway. Cin ameliorates collagen-induced arthritis in rats. Cin is a potential TCM-derived disease modifying anti-rheumatic herbal drug.