Cinnamaldehyde Induces the Expression of MicroRNA-1285-5p and MicroRNA-140-5p in Chondrocytes to Ameliorate the Apoptosis and Inflammatory Response

Abstract

Objective Cinnamaldehyde (CA) is an active ingredient of Wenyang Tongluo capsule. This study was performed to investigate the function of CA on human chondrocytes. Design Different doses of CA were used to treat C28/I2 cells, which were stimulated by interleukin-1β (IL-1β), and then the viability and apoptosis of the cells were examined by cell counting kit-8 and flow cytometry. Interleukin-6 (IL-6), interleukin-20 (IL-20), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Quantitative real-time reverse transcriptase polymerase chain reaction was performed to measure miR-1285-5p, miR-140-5p, IL-20, and high-mobility group box 1 (HMGB1) messenger RNA (mRNA) expression. Western blot assay was performed to detect IL-20, HMGB1, IKBα, phospho-IKBα, IKKα/β, and phospho-IKKα/β expression. Moreover, the relationships between miR-1285-5p and IL-20, as well as miR-140-5p and HMGB1, were validated by dual-luciferase reporter assay. Results CA promoted the viability and inhibited the apoptosis of C28/I2 cells stimulated by IL-1β and repressed IL-6, IL-20, and TNF-α levels. CA increased miR-1285-5p and miR-140-5p expression levels. MiR-1285-5p and miR-140-5p promoted the viability and inhibited the apoptosis and inflammation of C28/I2 cells. IL-20 was a target gene of miR-1285-5p, and HMGB1 was a target gene of miR-140-5p. Overexpression of IL-20 or HMGB1 could reverse the effect of CA on C28/I2 cells treated with IL-1β. In addition, HMGB1 increased phospho-IKBα and phospho-IKKα/β expression in IL-1β- and CA-treated C28/I2 cells. Conclusions CA protects chondrocytes via regulating miR-1285-5p/IL-20 axis and miR-140-5p/HMGB1/nuclear factor kappa B pathway.

Biological fate, functional properties, and design strategies for oral delivery systems for cinnamaldehyde

“…39,43 According to Li et al, CA could alleviate cartilage destruction in the C28/I2 human chondrocyte cell line via decreasing the mRNA expression levels of MMP-1, MMP-3 and MMP-13 as well as reducing the levels of p-p38 and p-JNK, demonstrating an anti-inflammatory effect in vitro and a protective effect on chondrocytes in vivo. 10 Mateen et al discovered that CA exerted an anti-inflammatory effect in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis by effectively inhibiting the secretion of proinflammatory cytokines TNF-α and IL-6 and regulating the equilibrium of cytokines secreted by Th1 and Th2 cells. 30 Another study stated that CA alleviated collagen-induced swollen paw volume in rats with arthritis by inhibiting the phosphorylation of janus kinase 2 (JAK2) and decreasing the expression of p-signal transducer and activator of transcription 1 (STAT1) and p-STAT3.…”

“…4 The cinnamic acid is then transported to the bark tissue and reduced to CA through a catalytic reaction. 5 CA has been reported to exhibit diverse pharmacological properties, including antioxidant, 6 cardioprotective, 7,8 antiinflammatory, 9,10 anti-obesity, 11,12 antitumor, 13,14 and antibacterial activities [15][16][17] (as shown in Fig. 1).…”

“…CA has been reported to exhibit diverse pharmacological properties, including antioxidant, 6 cardioprotective, 7,8 anti-inflammatory, 9,10 anti-obesity, 11,12 antitumor, 13,14 and antibacterial activities 15–17 (as shown in Fig. 1).…”