Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells

Abstract

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

Healing Effect of Vicenin-2 (VCN-2) on Human Dermal Fibroblast (HDF) and Development VCN-2 Hydrocolloid Film Based on Alginate as Potential Wound Dressing

“…We propose that such results might reflect the reasons of delaying inflammation reaction which lead to further deterioration effects on wound. The present results agreed with those reported by Choi et al and Vo et al [25], they found that inflammation occurs due to stimulation of NF-κB, iNOS, and COX-2; therefore, inhibited activation of these pro-inflammatory mediators have attenuated adverse inflammation related illness.…”

Anti-Allergic Effect of Oroxylin A from Oroxylum indicum Using in vivo and in vitro Experiments

“…Plates were then washed fourteen times and incubated with substrate solution for 15 min at room temperature. Stop solution was then added and absorbance was read at 450 nm ( Vo et al ., 2014 ).…”

Apocynin Suppresses Lipopolysaccharide‐Induced Inflammatory Responses Through the Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells

“…The present study showed that apocynin attenuated LPS‐induced IκB degradation in a concentration‐dependent manner preventing nuclear translocation of NF‐κB. Suppression of NF‐κB transcription mediated anti‐inflammatory properties of natural products against LPS‐induced inflammation in RAW264.7 cells [Vo et al, ]. However, further studies are necessary to clearly delineate the exact mechanism by which apocynin leads to the suppression of iNOS and COX‐2 expression.…”

“…Other signaling pathways such as PI3K/Akt may also be involved in LPS‐induced pro‐inflammatory responses [Ha et al, ]. Activation of Akt signaling pathway suppressed LPS‐induced inflammatory gene expressions and cytokine secretion [Vo et al, ], suggesting that multiple signaling pathways are involved in LPS‐induced inflammatory processes. Therefore, further studies are necessary to further understand the contribution of other signaling pathways to LPS‐induced inflammatory events.…”