Sophoridine inhibits endotoxin-induced acute lung injury by enhancing autophagy of macrophage and reducing inflammation

Abstract

Acute lung injury (ALI) is characterized by uncontrolled inflammation, which can lead to respiratory distress syndrome and cause patient death. In this study, we sought to determine the role of sophoridine, a compound purified from sophora, in ALI. A mouse model of ALI was established by treating mice with LPS through nonexposed tracheal instillation. After LPS‐induced mice were treated with sophoridine, LPS‐induced alveolar wall thickening, alveolar interstitial inflammatory exudation and thickening, and the degree of pulmonary edema were found to be inhibited. Macrophages play an important role in inflammation, and in vitro experiments have demonstrated that sophoridine reduces the LPS‐induced expression of inflammatory factors by macrophages, suggesting that sophoridine may inhibit lung inflammation in LPS‐treated mice through reduces the secretion of inflammatory factors. Further, treatment with sophoridine up‐regulated autophagy in macrophage cells in vitro and mouse lung tissues in vivo. LPS can bind to TLRs and activate the MyD88/NF‐κB pathways, leading to increased inflammation in the pathogenesis of ALI. Our findings revealed that sophoridine down‐regulated the expression of TLR4/MyD88/NF‐κB and mTOR mRNA and protein in mouse pulmonary tissue. Collectively, these findings indicate that sophoridine may inhibit LPS‐induced ALI by enhancing autophagy of macrophages and reducing inflammation.

Attenuation of the Severity of Acute Respiratory Distress Syndrome by Pomiferin through Blocking Inflammation and Oxidative Stress in an AKT/Foxo1 Pathway-Dependent Manner

“…Interstitial macrophages are differentiated from alveolar macrophages by their localization, regulating immune reactions and participating in the inflammation process. During ARDS, both alveolar macrophages and interstitial macrophages are activated, which could then release excessive proinflammatory cytokines and result in lung tissue injury [ 39 , 40 ]. ROS is a very important factor driving inflammatory response, which performs an integral role in the development of ARDS.…”

Research Progress on Autophagy Regulation by Active Ingredients of Traditional Chinese Medicine in the Treatment of Acute Lung Injury

“…and Sophora moocrorftinan with antitumour, anti-inflammatory and antiviral activities. 111 Studies have shown 112 that mice with LPS-induced ALI exhibit hyperaemia in the large alveolar wall, thickening of the lung interstitium, inflammatory cell infiltration, and increased expression of inflammatory factors (HMGB1, TNF-α, IL-6 and IL-1β) in lung tissue and serum. The expression of autophagy-related proteins was increased, autophagy flux was increased, and TLR4, MYD88, P65 and P-mTOR protein levels in lung tissues were also increased.…”

The Role of Macrophage Autophagy in Asthma: A Novel Therapeutic Strategy

“…Thus, it can be speculated that macrophage autophagy impedes the production of inflammatory mediators and alleviates inflammatory responses in asthma. Activation of autophagy macrophage by sophoridine, a natural compound, alleviates LPS-mediated inflammation and acute lung injury by suppressing the TLR4/NF- κ B and mTOR signaling pathways [ 58 ]. Further investigation of the regulation of macrophage autophagy in asthmatic inflammation could provide a promising therapeutic strategy for this disease.…”