Ginsenoside Rh2 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Regulating the TLR4/PI3K/Akt/mTOR, Raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 Signaling Pathways in Mice.

Yung-Hung Hsieh,Yuan-Shiun Chang,Jeng-Shyan Deng,Guan-Jhong Huang

doi:10.3390/nu10091208

Yung-Hung Hsieh, Yuan-Shiun Chang + Show 2 more

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https://doi.org/10.3390/nu10091208

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Journal: Nutrients	Publication Date: Sep 1, 2018
Citations: 69	License type: CC BY 4.0

Affiliation: China Medical University, Asian University

Abstract

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) has labeled it as one of the most important ginsenosides. The purpose of this study was to identify the anti-inflammatory and antioxidant effects of GRh2 using a lipopolysaccharide (LPS) challenge lung-injury animal model. GRh2 reduced LPS-induced proinflammatory mediator nitric oxide (NO), tumor necrosis factor-alpha, interleukin (IL)-1β, and anti-inflammatory cytokines (IL-4, IL-6, and IL-10) production in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and bronchoalveolar lavage fluid (BALF) protein content; total cell number also reduced in LPS-induced lung injury in mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1, and MEK protein expression, which corresponds with the growth of HO-1, Nrf-2, catalase, SOD, and GPx expression in LPS-induced lung injury. An in vivo experimental study suggested that GRh2 has anti-inflammatory effects, and has potential therapeutic efficacy in major anterior segment lung diseases.

Highlights

Acute lung injury (ALI) continues to produce the high mortality rate and mortality that it seems to be related to the shock, sepsis, and ischemia reperfusion, aspiration of gastric contents, major trauma and acute pancreatitis [1]
In the LPS-induced group of the lung specimens, neutrophils are infiltrating in the pulmonary vessel, edema of the interstitial space of the alveolar wall and those contexts causes alveolar epithelial cell damage. These improves of the pathological process by varying concentrations in ginsenoside Rh2 (GRh2) (5, 10 and 20 mg/mL) and Dex (10 mg/kg) groups mice, suggesting that GRh2 alleviated its pathological effects in LPS-induced ALI mouse model
The lung injury score showed GRh2 improved LPS induced inflammatory response (Fig. 1C). These results suggested that GRh2 evidenced by reduced inflammatory cell infiltration to protect the LPS challenge histopathological changes in the mice of lung tissues

Summary

Introduction

Acute lung injury (ALI) continues to produce the high mortality rate and mortality that it seems to be related to the shock, sepsis, and ischemia reperfusion, aspiration of gastric contents, major trauma and acute pancreatitis [1]. ALI induced either by hypoxic and ischemic stresses or bacterial endotoxin such as lipopolysaccharide (LPS), is occur with the stability of redox states can cause DNA damage, oxidative protein and lipid [2]. Activation of macrophage participate inflammatory responses in LPS inducement by releasing pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6], anti-inflammatory cytokines (IL-4 and IL-10) and proinflammatory mediator (NO) that relating to the sites of tissue injury in immune cell recruitment [5]. Toll-like receptor 4 (TLR4) is a transmembrane protein that belongs to the pattern recognition receptor for LPS from gram-positive bacteria and TLR4 activates the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) to induce the production of inflammatory mediators [6]. Phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (Akt)/ mechanistic target of rapamycin (mTOR) signaling pathway are an important intracellular mediator, which is critical for doi:10.20944/preprints201807.0426.v1

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