Regulatory Effect of Cinnamaldehyde on Monocyte/Macrophage-Mediated Inflammatory Responses

Abstract

Cinnamaldehyde (CA) has been known to exhibit anti-inflammatory and anticancer effects. Although numerous pharmacological effects have been demonstrated, regulatory effect of CA on the functional activation of monocytes and macrophages has not been fully elucidated yet. To evaluate its monocyte/macrophage-mediated immune responses, macrophages activated by lipopolysaccharide (LPS), and monocytes treated with proaggregative antibodies, and extracellular matrix protein fibronectin were employed. CA was able to suppress both the production of nitric oxide (NO) and upregulation of surface levels of costimulatory molecules (CD80 and CD69) and pattern recognition receptors (toll-like receptor 2 (TLR2) and complement receptor (CR3)). In addition, CA also blocked cell-cell adhesion induced by the activation of CD29 and CD43 but not cell-fibronectin adhesion. Immunoblotting analysis suggested that CA inhibition was due to the inhibition of phosphoinositide-3-kinase (PI3K) and phosphoinositide-dependent kinase (PDK)1 as well as nuclear factor-(NF-) κB activation. In particular, thiol compounds with sulphydryl group, L-cysteine and dithiothreitol (DTT), strongly abrogated CA-mediated NO production and NF-κB activation. Therefore, our results suggest that CA can act as a strong regulator of monocyte/macrophage-mediated immune responses by thiolation of target cysteine residues in PI3K or PDK1.

Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression

“…In addition, we found that CA treatment suppresses tumor growth in mice and vessel formation in tumors. CA reduced HIF-1a and VEGF expression in cancer cells, and it has been reported to have antioxidant and anti-inflammatory actions [19][20][21][51][52][53]. These collective findings suggest that CA could be an effective cancer therapeutic agent through its orchestrated actions on apoptosis and angiogenesis in cancer and vascular endothelial cells.…”

“…CA has been shown to have antioxidant, anti-microbial, and anti-diabetic effects [17][18][19]. Moreover, it has been reported to have chemopreventive activities against several tumors and anticancer functions by inhibiting proliferation and inducing apoptosis [20,21]. However, a role for CA in angiogenic regulation has not yet been defined.…”

Cinnamaldehyde derivatives inhibit degranulation and inflammatory mediator production in rat basophilic leukemia cells

“…Inhibitory effects of cinnamon water extract on phosphorylation of ERK1/2 and scavenger activity in macrophage has been revealed [26]. Cinnamaldehyde, the major constituents of Cinnamomi cortex [27], possesses versatile biological activities [17,18,[33][34][35]. In macrophage, cinnamaldehyde suppressed the production of pro-inflammatory mediators such as COX-2 and iNOS through attenuation of activation of ERK1/2, p38 and NF-κB [33,34].…”

“…Cinnamaldehyde, the major constituents of Cinnamomi cortex [27], possesses versatile biological activities [17,18,[33][34][35]. In macrophage, cinnamaldehyde suppressed the production of pro-inflammatory mediators such as COX-2 and iNOS through attenuation of activation of ERK1/2, p38 and NF-κB [33,34]. In addition, cinnamaldehyde inhibited activation of signaling pathway related with allergic inflammation in RBL-2H3 cells and mBMMCs [17,18].…”

Neuroprotective Effect of <i>trans</i>-Cinnamaldehyde on the 6-Hydroxydopamine-Induced Dopaminergic Injury

“…[12][13][14][15][16] As cinnamaldehyde showed the anti-inflammatory effect in macrophages, we speculated that TCA may exhibit a similar anti-inflammatory effect in microglia, which act as a sensor for pathological events in the central nervous system (CNS). 17,18) Therefore, we evaluated the effects of TCA on lipopolysaccharide (LPS)-induced nitric oxide (NO) release and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the BV2 microglial cells. We further investigated the neuroprotective efficacy of TCA on dopaminergic degeneration and its suppressive effects on the increased iNOS and COX-2 expressions, which were induced by a 6-hydroxydopamine (6-OHDA) injection to mice.…”