Oroxylin-A Rescues LPS-Induced Acute Lung Injury via Regulation of NF-κB Signaling Pathway in Rodents

Abstract

Background and PurposeSuccessful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality.Experimental ApproachRats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice.Key ResultsLPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate.Conclusion and ImplicationOroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.

Resolvin D1 Stimulates Alveolar Fluid Clearance through Alveolar Epithelial Sodium Channel, Na,K-ATPase via ALX/cAMP/PI3K Pathway in Lipopolysaccharide-Induced Acute Lung Injury

“…Pulmonary edema is a hallmark of LPS-induced ALI and a lifethreatening condition, consisting of various degrees of water and proteins, resulting from an imbalance between forces driving fluid into the airspaces and biological mechanisms for its removal (27,42). It is widely accepted that resolution of alveolar edema is the key step to patient survival (5).…”

Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates

“…reported by other compounds, such as inosine, 14 bupleurum polysaccharides, 21 proxylin A, 22 and quercetin, 23 and by other pyrrol compounds, such as T-686, an inhibitor of plasminogen activator inhibitor-1 that was associated with a mortality reduction in mice exposed to LPS. 24 However, none of those compounds had described any antiapoptotic activity in sepsisinduced lung injury.…”

Structure-Activity Association of Flavonoids in Lung Diseases

“…Although the control of lung ventilation as a protection strategy has considerably reduced mortality, no specific treatment is available; the number of young people who died because of ARDS is high and the treatment only considered the cause. Some evidence suggests that substances of the flavonoid class may have a modulatory effect in ARDS, but most of the studies are in experimental models [97,98].…”

“…Isolated from Scutellaria baicalensis [103], this compound mitigated reduced inflammation, elevated levels of TNF-α and NO in the plasma, alveolar edema and thickened alveolar septa through a post-treatment administration. Altogether, oroxylin-A (32) proved to be a potential drug for ameliorating lung inflammation induced by LPS [98].…”