Abstract
Background: Acute lung injury (ALI) is a complicated and severe lung disease, which is often characterized by acute inflammation. Poliumoside (POL), acteoside (ACT) and forsythiaside B (FTB) are phenylethanoid glycosides (PGs) with strong antioxidant, anti-inflammatory, and anti-apoptotic properties, which are extracted from Callicarpa kwangtungensis Chun (CK). The aim of this study was to investigate the protective effects of POL, ACT, and FTB against TNF-α-induced damage using an ALI cell model and explore their potential mechanisms. Methods and Results: MTT method was used to measure cell viability. Flow cytometry was used for detecting the apoptosis rate. Reactive oxygen species (ROS) activity was determined using fluorescence microscope. The expression of mRNA in apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) were tested by qPCR. The effects of POL, ACT, FTB on the activities of nuclear factor erythroid-2 related factor 2 (Nrf2), nuclear factor kappa-B (NF-κB) and the expression of their downstream genes were assessed by western blotting and RT-PCR in A549 cells. In the current study, POL, ACT, and FTB dose-dependently attenuated TNF-α-induced IL-1β, IL-6 and IL-8 production, cell apoptosis, the expression of apoptosis-related genes (Caspase 3, Caspase 8, and Caspase 9) and ROS activity. POL, ACT, and FTB not only increased in the mRNA levels of antioxidative enzymes NADPH quinone oxidoreductase (NQO1), glutamate cysteine ligase catalytic subunit (GCLC), heme oxygenase (HO-1), but also decreased the mRNA levels of IL-1β, IL-6 and IL-8. Furthermore, they upregulated the expression of Keap1 and enhanced the activation of Nrf2, while decreased the expression of phosphor-IκBα (p-IκBα) and nuclear p65. In addition, no significant changes were observed in anti-inflammatory and antioxidant effects of POL, ACT, FTB following Nrf2 and NF-κB p65 knockdown. Conclusion: Our study revealed that POL, ACT, and FTB alleviated oxidative damage and lung inflammation of TNF-α-induced ALI cell model through regulating the Nrf2 and NF-κB pathways.
Highlights
Acute lung injury (ALI), one of the common critical diseases in the clinical respiratory department, is often characterized by acute inflammation with complex etiology and mechanism (Butt et al, 2016)
The effects of POL, ACT, forsythiaside B (FTB) on the activities of nuclear factor erythroid-2 related factor 2 (Nrf2), nuclear factor kappa-B (NF-κB) and the expression of their downstream genes were assessed by western blotting and Real-Time Quantitative Polymerase Chain Reaction (RT-PCR) in A549 cells
Our study revealed that POL, ACT, and FTB alleviated oxidative damage and lung inflammation of TNF-α-induced ALI cell model through regulating the Nrf2 and NF-κB pathways
Summary
Acute lung injury (ALI), one of the common critical diseases in the clinical respiratory department, is often characterized by acute inflammation with complex etiology and mechanism (Butt et al, 2016). It frequently progresses to acute respiratory distress syndrome (ARDS) or even death (Komiya et al, 2017). Some agents of natural origin, such as medicinal plants and their secondary metabolites, have been reported to be potential alternatives for ALI treatment because of many pharmacological activities and few side effects (Favarin et al, 2013). Acute lung injury (ALI) is a complicated and severe lung disease, which is often characterized by acute inflammation. The aim of this study was to investigate the protective effects of POL, ACT, and FTB against TNF-α-induced damage using an ALI cell model and explore their potential mechanisms
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