Red ginseng polysaccharide attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of Nrf2/AMPK pathways

Main Article Content

Qiuhong Liu
Jinqiao Zhou
Jingrui Yang
Xiaoqin Zhang
Yuna Li
Li Zhang

Keywords

acute lung injury, endoplasmic reticulum stress, lipopolysaccharide, oxidative stress, red ginseng polysaccharide

Abstract

The present study elucidates the protective efficacy of red ginseng polysaccharide (RGP) against septic-associated acute lung injury (ALI), a critical condition exacerbated by oxidative stress and endoplasmic reticulum (ER) stress. Utilizing lipopolysaccharide (LPS)-induced mouse and cellular models, we assessed lung pathology through histological staining, injury scoring, and lung wet-to-dry ratios along with inflammatory cytokine levels. Cell viability and apoptosis were quantified using cell counting kit-8 and TUNEL assays, respectively, while fluorescence labeling was employed to gauge reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Our findings indicated that RGP markedly attenuated LPS-induced lung damage, inflammation, oxidative injury, ER stress, and apoptotic processes. Mechanistic insights revealed that RGP exerted its protective effects by activating the nuclear factor erythroid-2-related factor 2 (Nrf2)/adenosine monophosphate-activated protein kinase (AMPK) pathway in LPS-stressed lung tissues. Inhibition of Nrf2 or AMPK abrogated RGP’s benefits on apoptosis, ROS production, and MMP preservation in murine lung type II epithelial (MLE-12) cells, underscoring the Nrf2/AMPK-mediated mechanism of RGP’s action against LPS-induced ALI. These results underscore the potential of RGP as a novel therapeutic agent for sepsis-associated ALI.

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