Protective effect of acacetin on sepsis-induced acute lung injury via its anti-inflammatory and antioxidative activity

Abstract

Sepsis is a clinical syndrome with no effective protective or therapeutic treatments. Acacetin, a natural flavonoid compound, has anti-oxidative and anti-inflammatory effects which can potentially work to reduce sepsis. We investigated the potential protective effect of acacetin on sepsis-induced acute lung injury (ALI) ALI and dissect out the underlying mechanisms. Mice were divided into five groups: a sham group, a sepsis-induced ALI group, and three sepsis groups pre-treated with 20, 40, and 80 mg/kg body weight of acacetin. We found that acacetin significantly attenuated sepsis-induced ALI, in histological examinations and lung edema. Additionally, acacetin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice. Pulmonary myeloperoxidase (MPO) activity was lower in the acacetin-pre-treated sepsis groups than in the sepsis group. The mechanism underlying the protective effect of acacetin on sepsis is related to the regulation of certain antioxidation genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutases (SODs), and heme oxygenase 1 (HO-1).Taken together, our results indicate that acacetin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity, suggesting that acacetin may be a potential protective agent for sepsis-induced ALI.

Doxorubicin cardiomyopathy is ameliorated by acacetin via Sirt1‐mediated activation of AMPK/Nrf2 signal molecules

“…Other reports showed that acacetin has anti-inflammation, anti-tumour and antioxidative properties. 24,25 Our recent studies reported that acacetin and its water-soluble prodrug confer cardioprotection against hypoxia/reoxygenation insult in cardiomyocytes 14 and ischaemia/reperfusion injury in in vivo and ex vivo hearts. 13 Acacetin prodrug significantly improves myocardial function and inhibits ventricular arrhythmia induced by ischaemia/ reperfusion injury in rats; acacetin prevents ischaemia/reperfusion by increasing myocardial antioxidation and inhibiting inflammation and apoptosis.…”

Tetramethylpyrazine Showed Therapeutic Effects on Sepsis-Induced Acute Lung Injury in Rats by Inhibiting Endoplasmic Reticulum Stress Protein Kinase RNA-Like Endoplasmic Reticulum Kinase (PERK) Signaling-Induced Apoptosis of Pulmonary Microvascular Endothelial Cells

“…Caused by trauma, shock, and infection, sepsis is one of the life-threatening situations leading to multiple organ dysfunctions and failure. ALI is one of the typical organ injuries caused by sepsis, which is characterized by lung edema and intractable hypoxemia [ 17 ]. The molecular mechanisms of ALI are still unclear.…”

Plants as Sources of Anti-Inflammatory Agents

“…It is well-known that oxidative stress plays important role in endothelial dysfunction, lung disease, gastrointestinal dysfunction, and atherosclerosis, and inflammatory symptoms are involved in all these disorders [ 112 , 113 ]. Excessive pro-inflammatory cytokines and mitochondrial dysfunction induce oxidative stress, characterized by an imbalance between the effectiveness of antioxidant defense and the speed of ROS generation, causing a net overload of oxidants [ 114 , 115 , 116 ].…”