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

• Published in: PloS one 2018-04, Vol.13 (4), p.e0196405-e0196405
• Main Authors: Lu, Ying, Yu, Ting, Liu, Jingyao, Gu, Lina
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - pathology; Acute Lung Injury - prevention & control; Alveoli; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Apigenin - pharmacology; Apigenin - therapeutic use; Biochemistry; Biology and Life Sciences; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Bronchus; Care and treatment; Cellular signal transduction; Development and progression; Edema; Flavonoids; Genetic aspects; Health aspects; Heme; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hyperoxia; IL-1β; Inflammasomes; Inflammation; Injuries; Intensive care; Interleukin-1beta - metabolism; Ischemia; Laboratory animals; Leucine; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - toxicity; Lung diseases; Lungs; Male; Medicinal plants; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NRF2 protein; Oxidative stress; Oxidative Stress - drug effects; Oxygen; Oxygenase; Physiology; Plant tissues; Proteins; RAW 264.7 Cells; Reactive oxygen species; Reactive Oxygen Species - metabolism; Respiratory distress syndrome; RNA Interference; RNA, Small Interfering - metabolism; Rodents; siRNA; Trachea; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196405

A 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. ALI 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. Our 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. Vitexin suppresses LPS-induced ALI by controlling Nrf2 pathway.