Coelonin protects against PM_2.5‐induced macrophage damage via suppressing TLR4/NF‐κB/COX‐2 signaling pathway and NLRP3 inflammasome activation in vitro

Abstract

One of the important monitoring indicators of the air pollution is atmospheric fine particulate matter (PM 2.5 ), which can induce lung inflammation after inhalation. Coelonin can alleviate PM 2.5 -induced macrophage damage through anti-inflammation.However, its molecular mechanism remains unclear. We hypothesized that macrophage damage may involve the release of inflammatory cytokines, activation of inflammatory pathways, and pyrosis induced by inflammasome. In this study, we evaluated the anti-inflammation activity of coelonin in PM 2.5 -induced macrophage and its mechanism of action. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured by NO Assay kit and dichlorofluorescein-diacetate (DCFH-DA), and apoptosis were measured by Flow cytometry and TUNEL staining. The concentration of inflammatory cytokines production was measured with cytometric bead arrays and ELISA kits. The activation of NF-κB signaling pathway and NLRP3 inflammasome were measured by immunofluorescence, quantitative reverse transcription-polymerase chain reaction and western blot. As expected, coelonin pretreatment reduced NO production significantly as well as alleviated cell damage by decreasing ROS and apoptosis. It decreased generation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in PM 2.5 -induced RAW264.7 and J774A.1 cells. Moreover, coelonin markedly inhibited upregulating the expression of toll-like receptor (TLR)4 and cyclo-oxygenase (COX)-2, blocked activation of p-nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed expression of NLRP3 inflammasome, ASC, GSDMD, IL-18 and IL-1β. In conclusion, the results showed that coelonin could protect against PM 2.5 -induced macrophage damage via suppressing TLR4/NF-κB/ COX-2 signaling pathway and NLRP3 inflammasome activation in vitro.

Air-pollutant particulate matter 2.5 (PM2.5)-induced inflammation and oxidative stress in diseases: Possible therapeutic approaches

“…The OP-D exerts its anti-inflammatory effect through downregulation of NFB signaling and activation of AMPK activity as pretreatment of cells with AMPK inhibitor (Compound C, 10 µM) blocks anti-inflammatory activity of OP-D [80]. As the dihydrophenanthrene Coelonin, derived from the flowering plant Bletilla striata, is a known anti-inflammatory agent [81,82], its therapeutic efficacy in amelioration of PM2.5-induced inflammation has been evaluated [83]. Pretreatment with Coelonin (1.25, 2.5 or 5 µg/ml for 2h) ameliorates PM2.5 (200µ/ml for 18h)-induced inflammation, oxidative stress and pyroptosis of RAW264.7 and J774A.1 macrophages through suppression of Nlrp3 inflammasome, IL-6, TNF-, TLR4, COX2, and NF-B signaling [83].…”

“…As the dihydrophenanthrene Coelonin, derived from the flowering plant Bletilla striata, is a known anti-inflammatory agent [81,82], its therapeutic efficacy in amelioration of PM2.5-induced inflammation has been evaluated [83]. Pretreatment with Coelonin (1.25, 2.5 or 5 µg/ml for 2h) ameliorates PM2.5 (200µ/ml for 18h)-induced inflammation, oxidative stress and pyroptosis of RAW264.7 and J774A.1 macrophages through suppression of Nlrp3 inflammasome, IL-6, TNF-, TLR4, COX2, and NF-B signaling [83]. These results suggest that different natural compounds are effective in diminishing PM2.5-induced massive inflammation, oxidative stress, and pyroptosis.…”

Air-pollutant Particulate Matter 2.5 (PM2.5)-induced Inflammation and Oxidative Stress in Diseases: Possible Therapeutic Approaches

“…The Ophiopogonin D exerts its anti-inflammatory effect through downregulation of NF B signaling and activation of AMPK activity as pretreatment of cells with AMPK inhibitor (Compound C, 10 µM) blocks anti-inflammatory activity of Ophiopogonin D [80]. As the dihydrophenanthrene Coelonin, derived from the flowering plant Bletilla striata, is a known anti-inflammatory agent [81,82], its therapeutic efficacy in amelioration of PM2.5-induced inflammation has been evaluated [83]. Pretreatment with Coelonin (1.25, 2.5 or 5 µg/ml for 2h) ameliorates PM2.5 (200µ/ml for 18h)-induced inflammation, oxidative stress and pyroptosis of RAW264 and 1774A.1 macrophages through suppression of Nlrp3 inflammasome, IL-6, TNF-, TLR4, COX2, and NFkB signaling [83].…”

“…As the dihydrophenanthrene Coelonin, derived from the flowering plant Bletilla striata, is a known anti-inflammatory agent [81,82], its therapeutic efficacy in amelioration of PM2.5-induced inflammation has been evaluated [83]. Pretreatment with Coelonin (1.25, 2.5 or 5 µg/ml for 2h) ameliorates PM2.5 (200µ/ml for 18h)-induced inflammation, oxidative stress and pyroptosis of RAW264 and 1774A.1 macrophages through suppression of Nlrp3 inflammasome, IL-6, TNF-, TLR4, COX2, and NFkB signaling [83]. These results suggest that different natural compounds are effective in diminishing PM2.5-induced massive inflammation, oxidative stress, and pyroptosis.…”