Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-κB, MAPK and Inflammatory Cytokines

Abstract

Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.

Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy

“…The MAPK (ERK1/2, p38MAPK, and JNK) cascade has been shown to play an extracellular signal transduction, such as LPS-induced inflammatory cytokine production [8,32]. The defective activation or pharmacological inhibition of ERK or p38 reduces the production of LPS-induced pro-inflammatory cytokines [37].…”

“…Oxidative stress-mediated injury plays an essential role in lung failure. The protective mechanism is currently believed to be derived from antioxidant enzymes (catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx)) and nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase (HO-1) signaling against oxidative stress [ 8 ]. Nrf2 is an inducible protein with cytoprotective and antioxidant activities.…”

Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1/Nrf2/HO-1 Signaling

“…After the centrifugation, carefully transfer the supernatant to the new tube. The solution was recorded at 535 nm [15].…”

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…Then, the alveolar endothelial cells are damaged, resulting in the increased permeability of microvascular barriers, which is associated with the extravascular accumulation of protein-rich edema fluid as well as the transfer of leukocytes, erythrocytes and inflammasome-regulated cytokines into the alveolar space [ [22] , [23] , [24] ]. During the inflammatory process of ALI/ARDS, several signal transduction pathways such as nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), toll like receptors (TLRs), adrenergic receptors and JAK/STAT signaling pathways are involved [ [25] , [26] , [27] ]. Inhibition of NF-κB expression can inhibit the expression of inflammatory cytokines in the lungs, significantly reduce the inflammatory response in the lungs and improve the survival rate of lipopolysaccharide (LPS)-induced ALI mice [ 28 ].…”