Cutaneous ischemia-reperfusion (I/R) injury is one of the most crucial problems in flap surgery, which affects the survival of the skin flap and patient prognosis, luteolin, a plant derived flavonoid, has previously been shown to exert a variety of beneficial effects for reducing I/R injury in several organs. The aim of the present study was to evaluate the anti-inflammatory and anti-oxidative stress effects of luteolin on cutaneous I/R injury. The in vitro study were performed using a permanent human immortalized epidermal keratinocyte cell line (HaCaT), cells were cultured in the presence of luteolin and were then treated with hydrogen peroxide, the cell viability, mitochondrial membrane potential and the cell survival/apoptosis related signaling pathway activation were assessed to investigate the cytoprotective effects of luteolin. For in vivo experiments, skin flap I/R injury animal model was established in Sprague-Dawley rats, by measuring the area of flap survival, analyzing the expression of pro-inflammatory cytokine and evaluation of the histological changes in the skin tissue, the protective effects of luteolin on skin I/R injury were investigated. The function of protein kinase B (AKT) and heme oxygenase-1 (HO-1) activation on luteolin mediated I/R injury protection was assessed by administration of phosphoinositide-3-kinase/AKT inhibitor LY294002 and HO-1 inhibitor ZNPP. The results showed that luteolin treatment significantly increased the viability of HaCaT cells upon exposure to hydrogen peroxide, and the administration of luteolin in vivo significantly improved skin flap survival in the I/R injury rat model. The mechanisms underlying these beneficial effects included increased phosphoinositide-3-kinase/protein kinase B activation, improved expression of antioxidant enzyme, and scavenging the cytotoxic effects of reactive oxygen species (ROS). Taken together, the results suggested that luteolin preconditioning yielded significant protection against cutaneous I/R injury by protecting skin keratinocytes from ROS-induced damage.

Background: Neonatal pneumonia (NP) has a high fatality rate in neonatal illness. This research investigated the functions of emodin on lipopolysaccharide (LPS)-evoked inflammatory injury in WI-38 cells. Methods: Cell counting kit-8 (CCK-8) assay and flow cytometry were utilized for examining the impacts of LPS and emodin on viability and apoptosis, respectively. Taurine up-regulated gene 1 (TUG1) level was altered through cell transfection and investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, RT-qPCR, western blot and enzyme-linked immunosorbent assay (ELISA) were utilized for investigating expressions of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6. Western blot was carried out for investigating the levels of Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3 and NF-κB and p38MAPK pathway-related proteins. Results: LPS treatment restrained cell viability, enhanced apoptosis, and expressions of inflammation-related IL-6 and MCP-1. Emodin alleviated LPSevoked inflammatory injury and restrained the NF-κB and p38MAPK pathways. Furthermore, emodin positively regulated TUG1 expression and TUG1 silencing could reverse the efficacy of emodin on IL-6 and MCP-1 expressions. Finally, TUG1 regulates the expression of inflammatory factors through NF-κB and p38MAPK pathways. Conclusion: Emodin alleviated LPS-evoked inflammatory injury by raising TUG1 expression via NF-κB and p38MAPK pathways in WI-38 cells. K E Y W O R D S emodin, inflammatory damage, NF-κB and p38MAPK pathways, neonatal pneumonia, TUG1 1 | INTRODUCTION Neonatal pneumonia (NP) is the most familiar respiratory diseases in the neonatal stage. Most NP is caused by lung infections which are caused by inhalation of