Vitexin attenuates lipopolysaccharide-induced acute lung injury by controlling the Nrf2 pathway

Abstract

BackgroundA major feature of acute lung injury (ALI) is excessive inflammation in the lung. Vitexin is an active component from medicinal plants which has antioxidant and anti-inflammatory activities. Oxidative stress and inflammation play important roles in the pathophysiological processes in ALI. In the current study, we investigate the effect and potential mechanisms of Vitexin on lipopolysaccharide (LPS)-induced ALI.MethodsALI was induced by LPS intratracheal instillation in C57BL/6 wild-type mice and Nrf2 gene knocked down (Nrf2-/-) mice. One hour before LPS challenge, Vitexin or vehicle intraperitoneal injection was performed. Bronchoalveolar lavage fluid and lung tissues were examined for lung inflammation and injury at 24 h after LPS challenge.ResultsOur animal study’s results showed that LPS-induced recruitment of neutrophils and elevation of proinflammatory cytokine levels were attenuated by Vitexin treatment. Vitexin decreased lung edema and alveolar protein content. Moreover, Vitexin activated nuclear factor erythroid-2-related factor 2 (Nrf2), and increased the activity of its target gene heme oxygenase (HO)-1. The LPS-induced reactive oxygen species were inhibited by Vitexin. In addition, the activation of the nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) inflammasome was suppressed by Vitexin. However, these effects of Vitexin were abolished in the Nrf2-/- mice. Our cell studies showed that Vitexin enhanced the expression of Nrf2 and HO-1 activity. Moreover, reactive oxygen species (ROS) and IL-1β productions were reduced in Vitexin-treated cells. However, knockdown of Nrf2 by siRNA in RAW cells reversed the benefit of Vitexin.ConclusionsVitexin suppresses LPS-induced ALI by controlling Nrf2 pathway.

Glycine Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Regulating NLRP3 Inflammasome and NRF2 Signaling

“…Deficiency of NRF2 signaling leads to severe lung injury of mice in response to LPS exposure [38]. In contrast, enhanced protein levels of NRF2 have been reported to alleviate LPS-induced lung injury in mice [39,40]. In consistent with previous report [41], we found that glycine pre-administration reversed LPS-induced depletion of NRF2 and led to the increased protein level of genes implicated in cellular survival [42].…”

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…Vitexin attenuated RANKL-induced activation of MAPK signal pathways and NF-κB signaling pathways [51]. Also, the activation of Nrf2/HO-1 pathway is one of the mechanisms of vitexin to limit inflammation in a model of LPS-induced acute lung injury [52]. It was demonstrated by Chen et al, [114] in isoflurane-treated PC12 cells that vitexin is neuroprotective by downregulating the expression of TRPV1 and glutamate ionotropic receptor NMDA type subunit 2B (NR2B) protein expression.…”

“…The red arrows represent endogenous pathways that are inhibited by flavonoids resulting in reduced pain and inflammation. , NF-κB [51] and Nrf2 [52], Quercetin: MAPK [53], NF-κB [53][54][55], AKT [56], Nrf2 [33,54], and NLRP3 [57] and Naringenin: NF-κB [58][59][60] and Nrf2 [59,61,62]. (B) Ion channels expressed by neurons that are targeted by Vitexin, Quercetin, and Naringenin to reduce pain.…”

Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

“…Oxidative stress is characterized by the overproduction of ROS and it plays an important role in the pathogenesis of ALI [13]. ROS accumulation aggravates the inflammatory responses by promoting the expression of proinflammatory cytokines, and infiltration of inflammatory cells, leading to ALI [15,16]. In our study, SP treatment displayed a potent DPPH radical-scavenging activity and suppressed ROS generation in TNF-α-stimulated NCI-H292 cells.…”

“…Oxidative stress also plays a major role in the pathogenesis of lung injury in LPS-induced ALI [14,15]. Nuclear factor erythroid-2 related factor 2 (Nrf2) is a redox-sensitive transcription factor and it regulates the antioxidant and detoxifying enzymes [16]. It has been reported that Nrf2 plays an essential role in protecting cells against inflammatory and oxidative stress-mediated diseases [17,18].…”