Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells

Abstract

BackgroundLipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities.MethodsWe investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis.ResultsAEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells.ConclusionsAEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI.

Antioxidant, Antimicrobial, and Anti-Inflammatory Effects of Liriodendron chinense Leaves

“…Rhamnocitrin was more powerful in inhibiting IL-6 and COX-2 mRNA expression and increasing IL-10 mRNA expression. However, gaining a comprehensive understanding of the anti-inflammatory mechanism of fragransin B2, liriodendritol, and rhamnocitrin necessitates further in-depth experiments, such as investigations using human cell lines and additional clinical trials. − These facts evidenced that different compounds probably manifested different biological activities. The observed efficacy of LCLE was probably achieved by the synergistic effects of all of the compounds.…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Recently, the aqueous extract of Descuraniae Semen (AEDS) as well as Vitamin-D are reported to possess an anti-inflammatory effect in preclinical ALI models via targeting the ER stress markers IRE1α and ATF6, respectively, offering new insights for the treatment of ALI/ARDS [ 262 , 263 ]. However, a largest published randomised controlled trial showed no benefit of vitamin D on 90-day mortality in critically ill patients at high risk for ARDS [ 264 ].…”