Polygonatum sibiricum polysaccharides prevent LPS‑induced acute lung injury by inhibiting inflammation via the TLR4/Myd88/NF‑κB pathway

Abstract

Inflammation plays an important role in cases of acute lung injury (ALI), and the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway, which can be regulated by Polygonatum sibiricum polysaccharides (PSPs), is closely related to the dynamics of lipopolysaccharide (LPS)-induced inflammation. Thus, we sought to evaluate whether or not PSPs prevent LPS-induced ALI by way of inhibiting inflammation via the TLR4/NF-κB pathway in rats. We established an ALI rat model by tracheal instillation of LPS, and by pre-injection of PSPs into rats to examine PSPs in the ALI rat model. We found that PSPs attenuated LPS-induced lung pathological changes in ALI rats, decreased LPS-induced myeloperoxidase (MOP) activity, and elevated malondialdehyde (MDA) levels in lung tissue. However, PSPs also decreased the LPS-induced increase in the neutrophil ratio, and decreased inflammatory factor levels in bronchoalveolar lavage fluid (BALF). Moreover, PSPs decreased LPS-induced increases in inflammatory factors measured by mRNA expression, and altered the levels of expression of TLR4, medullary differentiation protein 88 (Myd88), p-IKB-α/IKB-α and p-p65/p65 proteins in lung tissue. In vitro, PSPs also reduced apoptosis induced by LPS in BEAS-2B cells by suppressing inflammation through its effect of inhibiting the TLR4/NF-κB pathway. In conclusion, our results suggest that PSPs may be a potential drug for effective treatment of LPS-induced ALI, due to the ability to inhibit inflammation through effects exerted on the TLR4/Myd88/NF-κB pathway.

All‑trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury

“…Furthermore, according to the KEGG database, there are many pathways downstream of CD14/TLR4 receptors ( Fig. 4B ), among which the NF-κB pathway serves a key role in ALI ( 27 , 28 ). Therefore, the mRNA and proteins of the NF-κB pathway were detected using RT-qPCR and WB.…”

The Preventive Effects of Lactobacillus casei on Acute Lung Injury Induced by Lipopolysaccharide

“…ALI is caused by various direct or indirect factors with the characteristics of diffuse interstitial lung and alveolar edema, about 30% to 50% of the cases are caused by severe infection [ 10 ]. The inflammatory response of lung tissue after ALI can be seen as a series of stress responses of lung tissue to injury, including increased capillary permeability of lung tissue, liquid and plasma protein leakage and a large number of white blood cells migrated to the inflammatory area [ 16 ].…”

“…The positive DEX + LPS control group was given dexamethasone 2 mg/kg by intraperitoneal injection 24 h before modeling. In reference to a previous report [ 10 ], for the LPS model group, the positive DEX + LPS control group and the L. casei + LPS experimental group, LPS (2 mg/kg of each mouce, Escherichia coli 055:B5, purchased from Sigma Corporation) was dissolved in 100 μL of normal saline, thereafter injected intraperitoneally to construct ALI model, and the normal group was injected with the same volume (100 μL) of normal saline. After 24 h, mice were euthanized with anhydrous ether, then blood was collected via retro-orbital route and lungs were removed together.…”

Lychee seed polyphenol protects blood–retinal barrier by increasing tight joint proteins and inhibiting the activation of TLR4/MYD88/NF-κB-mediated NLRP3 inflammasome

“…In addition, MYD88 induces the transduction of NF-κB from cytoplasm to nucleus, and initiates gene transcription and protein synthesis of various inflammatory cytokines to regulate the inflammatory responses (Wang et al, 2015). Emerging studies have shown that the TLR4/MYD88/NF-κB signalling pathway is one of the important pathways that regulate inflammatory response, and the activation of this pathway leads to the release of pro-inflammatory factors, including TNF-α, IL-1β, IL-6, IL-10 and IL-12 (Dolinay et al, 2012;Liu, Zhao, et al, 2020;Montravers et al, 1995). Therefore, the downregulation of TLR4/MYD88/NF-κB signal inhibits the inflammatory responses (Liu et al, 2012;Peng et al, 2015;Wang et al, 2016).…”