Nerolidol Suppresses the Inflammatory Response during Lipopolysaccharide-Induced Acute Lung Injury via the Modulation of Antioxidant Enzymes and the AMPK/Nrf-2/HO-1 Pathway

Abstract

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway

“…The dioscin treated mMECs for different time periods (0, 0.5, 1, 3, 6, and 12 h), and the results showed that dioscin increased the protein expression of total Nrf2 and nuclear Nrf2 and phosphorylation of AMPK and HO-1 (Figures 5(a) and 5(c) – 5(f) ), decreased the protein of Nrf2 in the cytoplasm, and reduced reactive oxygen (Figures 5(a) , 5(b) , and 5(g) ). Previous studies suggested that AMPK is an upstream of Nrf2 [ 34 ]. The results showed dioscin also promoted AMPK phosphorylation.…”

Protective Effects of Kirenol against Lipopolysaccharide-Induced Acute Lung Injury through the Modulation of the Proinflammatory NFκB Pathway and the AMPK2-/Nrf2-Mediated HO-1/AOE Pathway

“…The content of intracellular ROS expression is regulated by at least two types of AOEs. The first type comprises enzymes are associated with ROS scavenger, containing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase [ 3 , 4 ]. The second type comprises oxidative stress-induced enzyme, such as heme oxygenase-1 (HO-1) [ 4 , 5 ].…”

“…The first type comprises enzymes are associated with ROS scavenger, containing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase [ 3 , 4 ]. The second type comprises oxidative stress-induced enzyme, such as heme oxygenase-1 (HO-1) [ 4 , 5 ]. Expression of SOD, GPx, catalase, and HO-1 is regulated by nuclear factor erythroid 2–related factor 2 (Nrf2), which is the transcription factor and downstream factor of 5’AMP-activated protein kinase-2 (AMPK2).…”

“…In addition, the intracellular oxidative stress leads to the secretion of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) through the activation of nuclear factor (NF)-κB, a proinflammatory transcription factor [ 6 , 7 , 8 ]. The inflammatory response in ALI is exacerbated by the generation of ROS and proinflammatory cytokines [ 4 , 7 , 8 ].…”

Acetylated Polysaccharides From Pleurotus geesteranus Alleviate Lung Injury Via Regulating NF-κB Signal Pathway

“…Thus, inhibiting inflammation is an important link for the prevention of ALI. Furthermore, previous reports have shown that ROS can produce lipid peroxidation by binding to polyunsaturated fatty acids in the cell membrane, resulting in producing highly cytotoxic malondialdehyde (MDA), which subsequently destroys the stability of the biofilm and increases its permeability, leading to cell damage or necrosis [16][17][18]. Both lipid peroxidation and excessive inflammation response caused by oxidative stress are important reasons of ALI, and the pathological changes of ALI are characterized by oxidative damage, excessive inflammation, and lipid peroxidation [19].The pathogenesis of and therapeutic drugs for ALI are have been the focus of current research for 30 years [20][21][22][23][24].…”