Curcumin Attenuates Pulmonary Inflammation in Lipopolysaccharide Induced Acute Lung Injury in Neonatal Rat Model by Activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) Pathway

Abstract

BackgroundThis study aimed to investigate the therapeutic effect of curcumin in lipopolysaccharide (LPS) induced neonatal acute lung injury (ALI) and the possibly associated molecular mechanisms.Material/MethodsALI neonatal animal model was established by using LPS. Curcumin and/or peroxisome proliferator-activated receptor γ (PPARγ) inhibitor BADGE (bisphenol A diglycidyl ether) were administrated to animals. Lung edema was evaluated by PaO2 and lung wet/dry weight ratio (W/D) measurements. EMSA was used to determine the PPARγ activity. Levels of high-mobility group box 1 (HMGB1), secretory receptor for advanced glycation end products (RAGE), tumor necrosis factor α (TNFα), interleukin 6 (IL6), and transforming growth factor β1 (TGFβ1) in bronchoalveolar lavage fluid (BALF) were examined by ELISA. Western blotting was used to evaluate the expression levels of HMGB1, RAGE, heme oxygenase 1 (HO1), TNFα, IL6, and TGFβ1 in lung tissue.ResultsCurcumin administration significantly improved lung function by increasing PaO2 and decreasing W/D in neonatal ALI rats. Curcumin treatment upregulated the PPARγ activity and expression level of HO1 which were suppressed in lung tissue of neonatal ALI rats. Elevated levels of HMGB1, RAGE, TNFα, IL6, and TGFβ1 in both lung tissue and BALF from neonatal ALI rats were decreased dramatically by curcumin treatment. PPARγ inhibitor BADGE administration impaired curcumin’s alleviation on lung edema, inhibitory effects on inflammatory cytokine expression and recovery of PPARγ/HO1 signaling activation.ConclusionsCurcumin alleviated lung edema in LPS-induced ALI by inhibiting inflammation which was induced by PPARγ/HO1 regulated-HMGB1/RAGE pro-inflammatory pathway.

The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

“…Mechanistically, curcumin protects the lung by inhibiting inflammation and production of ROS through regulation of multiple signaling pathways engaging peroxisome proliferatoractivated receptor γ (PPARγ) (Cheng et al, 2018), JNK (Xiao et al, 2019), NF-κB (Suresh et al, 2012;Wang et al, 2018), and Nrf2 (Dai et al, 2018;Han et al, 2018). Notably, the role of curcumin in regulating Nrf2/HO-1 has been reported in IAV infection (Dai et al, 2018;Han et al, 2018).…”

Curcumin (a constituent of turmeric): New treatment option against COVID‐19

“…Curcumin is used as a spice in foods and for different purposes such as cosmetic and pharmaceutical industries in world (Hosseini & Hosseinzadeh, 2018). Curcumin has several pharmacological effects such as antioxidant, anticancer, antibacterial, antiviral, and antidiabetic effects (Fan et al., 2015; Moghadamtousi et al., 2014; Zhu et al., 2017), as well as anti‐inflammatory activity (Cheng, Yang, Hu, Zhu, & Liu, 2018). As the potential role of curcumin to treat many inflammatory disorders, at the first step we will describe all effects of curcumin that may be useful to treat COVID‐19, and then, we explain the possible molecular mechanisms of it.…”

MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway

“…The aforementioned studies have revealed that miRNAs exert protective effects against lung injury via repressing inflammatory responses. Moreover, a number of studies have indicated that attenuating pulmonary inflammation ameliorated acute lung injury in neonatal animal models ( 32-34 ). The present research confirmed that miR-490-3p was significantly downregulated in the LPS-induced neonatal ALI rat model.…”