Anti-inflammatory action of Athyrium multidentatum extract suppresses the LPS-induced TLR4 signaling pathway. (10th May 2018)

• Record Type: Journal Article
• Authors: Han, Xiong-Zhe; Ma, Rui; Chen, Qi; Jin, Xin; Jin, Yuan-Zhe; An, Ren-Bo; Piao, Xuan-Mei; Lian, Mei-Lan; Quan, Lin-Hu; Jiang, Jun
• Is Part Of: Journal of ethnopharmacology. Volume 217(2018)
• Page Start: 220
• Page End: 227
• Publication Date: 2018-05-10
• Subjects: LPS lipopolysaccharide -- ALI acute lung injury -- BALF bronchoalvelar lavage fluid -- NO nitric oxide -- PGE2 prostaglandin E2 -- iNOS inducible nitric oxide synthase -- COX-2 cyclooxygenase -- TLR4 toll-like receptor 4 -- TNF-α tumor necrosis factor-α -- IL interleukin -- IFN interferons -- qPCR quantitative PCR -- HPLC high performance liquid chromatography -- ELISA enzyme linked immunosorbent assay -- MAPK mitogen-activated protein kinase -- NF-κB nuclear factor kappa B -- IκB-α NF-κB inhibitor alpha -- DEX dexamethasone; Athyrium multidentatum -- Inflammation -- Acute lung injury -- Macrophage -- MyD88 -- TRIF; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.02.031
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The aerial part of Athyrium multidentatum (Doll.) Ching (AM) is widely used in the northeastern region of China as an edible wild herb, but its medicinal value, especially its anti-inflammatory effect, has not been fully explored. Aim of the study: To investigate the anti-inflammatory activity of AM and clarify the anti-inflammatory mechanism involving the TLR4 signaling pathway using a lipopolysaccharide (LPS)-induced inflammatory model. Materials and methods: AM ethanol extract was used as the experimental material to investigate the effect that the extract has on the production of pro-inflammatory mediators (NO, PGE2, TNF-α, IL-1β and IL-6); changes in LPS-induced peritoneal macrophages (PMs); and TLR4-mediated intracellular events, including MAPKs (ERK, JNK, and p38) and IκB-α in the MyD88-dependant pathway and IRF3, STAT1, and STAT3 in the TRIF-dependent pathway. In in vivo experiments, we established an LPS-induced acute lung injury (ALI) model and investigated the cell count and cytokine (TNF-α, IL-1β and IL-6) levels in bronchoalvelar lavage fluid (BALF) of C57BL6 mice. Histological changes in the lung tissues were observed with H&E staining. Results: AM extract inhibited NO and PGE2 by suppressing their synthetase (iNOS and COX-2) gene expression in LPS-induced PMs; the secretion of IL-6, IL-1β, and TNF-α also deceased via the down-regulation of mRNA levels. Furthermore, the TLR4-mediated intracellular events involved the phosphorylated forms of MAPKs (ERK, JNK) and IκB-α in the MyD88-dependent pathway and the TRIF-dependent pathway (IRF3, STAT1, STAT3), and the relevant proteins were expressed at low levels in the AM extract groups. In in vivo experiments, the cell count and cytokine (TNF-α, IL-1β and IL-6) levels in BALF decreased significantly in a dose-dependent manner in the AM extract groups. The lung tissue structure exhibited dramatic damage in the LPS group, and the damaged area decreased in the AM extract groups; in particular, the effect of 10 mg/kg extract was similar to that of the positive control dexamethasone (DEX). Conclusion: The findings demonstrate that AM protects against LPS-induced acute lung injury by suppressing TLR4 signaling, provide scientific evidence to support further study of the safety of anti-inflammatory drugs and indicate that AM can be used as an anti-inflammatory and anti-injury agent to prevent pneumonia caused by microbial infection. Graphical abstract: