Andrographolide Protects against LPS-Induced Acute Lung Injury by Inactivation of NF-κB

Abstract

BackgroundNuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro.Methods and ResultsIn vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro.ConclusionsThese results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ–Induced IL-27 and Airway Hyperresponsiveness in Mice

“…It binds specifically to the DNA binding subunit p50 at Cys 62 residue of the NF-kB complex, preventing the complex from binding to DNA for gene transcription (39). It has been shown that andrographolide suppressed LPS-induced p65 phosphorylation, p65 nuclear translocation, and NF-kB DNA binding activity in mouse MEL-12 epithelial cells and Raw 264.7 cells (40,41). However, in the present study andrographolide could not inhibit combined LPS/IFN-g-stimulated p65 phosphorylation in the Raw 264.7 cell line (data not shown).…”

Ethanol, ethyl and sodium pyruvate decrease the inflammatory responses of human lung epithelial cells via Akt and NF-κB in vitro but have a low impact on hepatocellular cells

“…The negative effects of alcohol consumption have been linked to an increased inflammatory response, including increased cytokine release (14,15,37,38). Pro-inflammatory cytokines such as IL-1β, TNF, IL-6 and IL-8 have been identified as important contributors to the pathogenesis of organ damage, including lung as well as liver injury in models of acute inflammation (17)(18)(19)(39)(40)(41)(42). Together with IL-6, IL-8 binds to molecules that are involved in neutrophil activation, trafficking and infiltration of tissues in models of acute lung and liver injury (18,43).…”

Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression

“…0.05 in inactive elastase-treated arteries postoperative at day 14). The in vivo dosage of Andro in the literature ranges from 1 to 100 mg/kg body weight, with 5 mg/kg body weight (used in the current study) as a commonly used dosage, which is considerably lower than the LD 50 for intraperitoneally administered andrographolide (11.6 g/kg body weight) (Handa and Sharma, 1990;Wang et al, 2007;Hsieh et al, 2011;Zhu et al, 2013). At the selected time points, mice were euthanized by CO 2 inhalation.…”