Nuciferine Ameliorates Inflammatory Responses by Inhibiting the TLR4-Mediated Pathway in Lipopolysaccharide-Induced Acute Lung Injury

Abstract

Acute lung injury (ALI) is a complex syndrome with sepsis occurring in critical patients, who usually lack effective therapy. Nuciferine is a primary bioactive component extracted from the lotus leaf, and it displays extensive pharmacological functions, including anti-cancer, anti-inflammatory, and antioxidant properties. Nevertheless, the effects of nuciferine on lipopolysaccharide (LPS)-stimulated ALI in mice has not been investigated. ALI of mice stimulated by LPS was used to determine the anti-inflammatory function of nuciferine. The molecular mechanism of nuciferine was performed on RAW264.7 macrophage cells. The results of pathological section, myeloperoxidase activity and lung wet/dry ratio showed that nuciferine alleviated LPS-induced lung injury (p < 0.05). qRT-PCR and ELISA experiments suggested that nuciferine inhibited TNF-α, IL-6, and IL-1β secretion in tissues and RAW264.7 cells but increased IL-10 secretion (p < 0.05). Molecular studies showed that TLR4 expression and nuclear factor (NF)-κB activation were both inhibited by nuciferine treatment (p < 0.05). To further investigate the anti-inflammatory mechanism of nuciferine, TLR4 was knocked down. When TLR4 was silenced, LPS induced the production of IL-1β, and TNF-α was markedly decreased by TLR4-siRNA and nuciferine treatment in LPS-induced RAW264.7 cells (p < 0.05). These results suggested that nuciferine had the ability to protect against LPS-stimulated ALI. Thus, nuciferine may be a potential drug for treating LPS-induced pulmonary inflammation.

Euphorbia cuneata Represses LPS-Induced Acute Lung Injury in Mice via Its Antioxidative and Anti-Inflammatory Activities

“…Furthermore, recruitment of inflammatory cells contributes to increase of the alveolar-capillary barrier permeability and lung edema. Results of this study were in line with previous research [ 2 , 10 , 26 ], as LPS induced marked pulmonary edema presented by increased lung W/D ratio. The total protein content in the BALF, as another index of epithelial permeability and pulmonary edema [ 2 ], was highly increased in the BALF of mice exposed to LPS.…”

“…LPS activates reactive oxygen species (ROS) generation and the release of proteases. Furthermore, LPS induces the activation of NF-κB signaling pathway and cytokine release [ 10 , 11 ]. Inflammatory mediators activate overproduction of ROS, leading to more oxidative damage.…”

Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells

“…A wide variety of phytochemicals derived from natural plant have anti-inflammatory effects, such as phenolics, terpenolids, and alkaloids [ 19 ]. Nuciferine, an alkaloid found in the lotus leaves, exerted a protective effect against inflammation, in vivo [ 20 ] and in vitro [ 21 ]. Our results showed that nuciferine decreased the expression of inflammatory cytokines IL-6 and TNFα, in both protein and gene levels, dose dependently, in the LPS-treated RAW264.7 cells, indicating that nuciferine had potential anti-inflammatory effects.…”

Identification and Functional Analysis of Long Non-coding RNAs in Human Pulmonary Microvascular Endothelial Cells Subjected to Cyclic Stretch

“…It has been reported that TNFAIP3 may stabilize the endothelial barrier by regulating the expression of VE-cadherin in acute lung injury (ALI) (Soni et al, 2018 ). Previous studies have also indicated that endothelial cells-expressed TLR4 increased vascular permeability and inflammatory responses in the early stages of ALI and/or ARDS (Tauseef et al, 2012 ; Wu et al, 2017 ; Peng et al, 2019 ). Its mechanism of action was likely to be that TLR4 induced the immune response by activating NF-κB signaling pathway via phosphorylating IRAK1 and IRAK2.…”