Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF‐κB signaling pathway in vivo and in vitro

Abstract

Background and Objectives: Sepsis that arises from uncontrolled pulmonary inflammation could induce acute lung injury (ALI), leading to the high death rate. Dachengqi decoction (DCQD) is a common traditional Chinese herbal medicine with strong anti-inflammatory effects. The current study aimed to explore the effect of DCQD on the inflammatory cytokines production, the aquaporin-1 (AQP-1) and AQP-5 protein expression in lipopolysaccharide (LPS)-induced ALI models, and the potential mechanisms underlying its effects.Methods: Sprague-Dawley rats and HULEC-5a cells were used as study models in the research. To detect related molecules in the study, the real-time polymerase chain reaction analysis, cell counting kit-8 assay, Western blot analysis, and enzyme-linked immunosorbent assay were performed.Results: DCQD could inhibit the expression of LPS-induced inflammatory cytokines, including interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α), in lung tissues and could reduce pulmonary edema by upregulating the expression of AQP-1 and AQP-5 in rats with LPS-induced ALI. Moreover, the results suggested that the toll-like receptor 4 (TLR4)/NF-κB signaling is indispensable for DCQD to increase the expression of AQP-1 and AQP-5 and inhibits the production of IL-6, IL-8, and TNF-α in LPS-induced HULEC-5a cells. Conclusion:The results of our study suggested that DCQD suppresses the TLR4/NF-κB signaling pathway, increases the protein expression of AQP-1 and AQP-5, and inhibits the production of inflammatory cytokines, by which it may alleviate the inflammatory reactions in ALI and benefit the treatments. K E Y W O R D S acute lung injury (ALI), aquaporin-1 (AQP-1), aquaporin-5 (AQP-5), Dachengqi decoction (DCQD), inflammatory cytokines 1 | INTRODUCTION Acute lung injury (ALI), its severe complication, and pulmonary edema are acute and life-threatening diseases caused by a variety of factors, including trauma, pneumonia, shock, and sepsis; the high mortality rate remains unresolved. 1,2 A major cause of ALI is that the intestinal barrier function of patients with sepsis is often damaged. A large amount of bacteria and endotoxins in the intestinal tract invade the blood circulation through J Cell Biochem. 2019;120:8956-8964. wileyonlinelibrary.com/journal/jcb 8956 |

MicroRNA‑93 contributes to the suppression of lung inflammatory responses in LPS‑induced acute lung injury in mice via the TLR4/MyD88/NF‑κB signaling pathway

“…TLR4 is a target of miR-93 in RAW264.7 cells. According to previous research, TLR4 is a common receptor of LPS, and plays important roles in the inflammatory response in ALI (38)(39)(40)(41)(42). Through bioinformatics prediction using TargetScan 7.0 and miRanda, the present study found that miR-93 directly targeted the TLR4 gene and that the target sequences were highly conserved among species (Fig.…”

Penehyclidine Hydrochloride Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Ameliorating Apoptosis and Endoplasmic Reticulum Stress

“…4,5 Several types of studies have confirmed that continued LPS can contribute to severe acute or long-lasting lung impairment, such as lung ultrastructural changes, restoration, and pulmonary functional disorder, which is more critical than that formed through LPS itself. 6,7 Results have confirmed that LPS-induced cell apoptosis occurs because of damage from the sudden release of subsequent reactive oxygen species, which plays a crucial role in LPS-induced ALI. 8 Numerous cascades control apoptosis (a type of automatic cell death).…”

MicroRNA‑17 contributes to the suppression of the inflammatory response in lipopolysaccharide‑induced acute lung injury in mice via targeting the toll‑like receptor 4/nuclear factor‑κB pathway

“…reported that the inhibition of the TLR4 signaling pathway suppressed the production of inflammatory cytokines, thereby improving ALI in rats (28). He et al demonstrated that the LPS/TLR4 axis can activate the NF-κB signaling pathway, resulting in inflammatory cell infiltration (44).…”

“…3A and B, TLR4 was identified as a potential target gene of miR-17, with the target site located in the 3'-UTR of TLR4 mRNA. It is well known that TLR-4 is a common receptor of LPS, and its downstream signaling effector, NF-κB, is closely associated with inflammatory response in ALI (14,(27)(28)(29)(30). Thus, TLR4 was selected for the subsequent investigation.…”