Astragalus membranaceus and Salvia miltiorrhiza Ameliorate Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating the Toll-Like Receptor 4/Nuclear Factor-Kappa B Signaling Pathway.

Li Qin,Min Li,Cheng-Yong Xu,Jian Feng,Hong-Ling Tan,Yong-Qi Dou,Yu-Guo Wang

doi:10.1155/2018/3017571

Abstract

Astragalus membranaceus and Salvia miltiorrhiza (AM/SM) are well used in Traditional Chinese Medicines (TCM) for nourishing Qi and activating blood circulation method. From TCM theory, the pathogenesis of acute lung injury (ALI) was determined as Qi deficiency and blood stagnation. In this study, we are aiming to investigate the protective and therapeutic effects of AM/SM on a rat model of lipopolysaccharide- (LPS-) induced ALI in rats and to elucidate potential molecular mechanisms. ALI was induced by intratracheal instillation of LPS (5 mg/kg) in Sprague–Dawley rats. SM/AM was given orally before and after LPS administration. Results demonstrated that AM/SM attenuated lung histopathological changes induced by LPS, decreased wet/dry weight ratios and protein concentrations, and inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in BALF. Moreover, AM/SM significantly downregulated protein and mRNA expression of toll-like receptors 4 (TLR-4), interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear factor-kappa B (NF-κB/p65). These findings suggest that AM/SM showed protective and therapeutic effects in LPS-induced ALI rat through modulating TLR-4 signaling pathways. Nourishing Qi and activating blood circulation may be a beneficial treatment for ALI.

Highlights

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are characterized by uncontrolled hyperinflammatory responses in the lung airspaces and lung parenchyma and involves alveolar capillary membrane damage, increased vascular permeability, neutrophils recruitment, pulmonary edema, and respiratory failure [1,2,3]
Lung wet/dry ratios and bronchoalveolar lavage fluid (BALF) protein concentrations significantly increased after LPS challenge compared with the sham group (P < 0.01) (Figures 1 and 2)
AM/SM significantly downregulated protein and mRNA expression of toll-like receptors 4 (TLR-4), interleukin-1 receptor-associated kinase-1 (IRAK-1), and NF-κB. These results suggest that the effects of AM/SM on LPS-induced ALI are possibly because of its ability to modulate toll-like receptor superfamily (TLRs)-4 signaling pathways and that this particular method for nourishing Qi

Summary

Introduction

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are characterized by uncontrolled hyperinflammatory responses in the lung airspaces and lung parenchyma and involves alveolar capillary membrane damage, increased vascular permeability, neutrophils recruitment, pulmonary edema, and respiratory failure [1,2,3]. As the primary component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), is an important risk factor for acute inflammatory responses and overwhelming innate immunity in ALI [6]. The toll-like receptor superfamily (TLRs), a major connective factor between innate and adaptive mucosal immune responses [8], can recognize pathogen-associated molecular patterns (PAMPs), such as TLR-4 recognition of LPS. Once stimulated by LPS, TLR4 is activated and recruits the adaptor molecule myeloid differentiation primary response gene 88 (MyD88) to the cytoplasmic domain of the receptor, which subsequently

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