Photodynamic anti-inflammatory activity of azulene derivatives on mammalian macrophages and their intracellular mechanism of action

Abstract

Azulene derivatives have been studied previously as photodynamic therapy agents. They have anti-cancer, anti-microbial and anti-inflammatory activities. Together with their photodynamic activity they enable more control on their activation which aims to decrease possible side effects that have been encountered with their constitutively active drug counterparts. In our current study we focused on photodynamic anti-inflammatory activities of two azulene derivatives whose synthesis methods were described before. We found that when mammalian macrophages J774.2 cells were incubated with these two derivatives in the presence of LPS in dark conditions, these molecules had anti-inflammatory activity at their highest concentrations based on ELISA results on the pro-inflammatory cytokine levels. After light application, both derivatives exerted strong anti-inflammatory activities by substantially decreasing the TNF, IL6, GMCSF and IL12p40 cytokine production levels. When the intracellular mechanism of action for both derivatives was tested, only one of them acted through p38 and PI3K pathways whereas the other derivative did not affect either of these pathways. Our results suggest that these two azulene derivatives can be utilized as photodynamic anti-inflammatory drug candidates.