Discovery medicine · 2025
Glycyrrhizic Acid Ameliorates Sepsis-Induced Acute Lung Injury Through Suppression of Endoplasmic Reticulum Stress.
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Fang Ling, Wang Xuepan, Guan Wei
Аннотация
BACKGROUND: Sepsis-mediated acute lung injury (ALI) has a high mortality rate, and glycyrrhizic acid (GA) possesses diverse pharmacologic activities. Herein, we investigated the role of GA in attenuating sepsis-triggered ALI.
METHODS: Septic ALI was induced by cecal ligation and puncture (CLP). Mice were assigned into 5 groups with varied treatments. Their time of death was recorded every 6 hours after surgery. The wet/dry (W/D) weight ratio of the lung was measured. Observation of lung tissues was conducted by hematoxylin and eosin (HE) staining. Protein concentration in bronchoalveolar lavage fluid (BALF), levels of inflammatory cytokines, and production of reactive oxygen species (ROS) were detected by bicinchoninic acid (BCA), enzyme-linked immunosorbent assay, and dihydroethidium (DHE) staining, respectively. Endoplasmic reticulum (ER) stress-related genes, heme oxygenase-1 (HO-1), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) levels were quantified by western blot.
RESULTS: GA remarkably elevated survival rate and mitigated lung injury (p < 0.05). CLP markedly increased the W/D weight ratio and BALF protein concentration, while GA did the opposite (p < 0.05). CLP promoted interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), phosphorylation of eIF2α (p-eIF2α), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), the phosphorylation level of JAK/STAT3, along with DHE intensity, while GA showed opposite effects (p < 0.01). Additionally, GA markedly enhanced the HO-1 level (p < 0.05).
CONCLUSION: GA holds promise for future improvements in treating sepsis-induced ALI.
METHODS: Septic ALI was induced by cecal ligation and puncture (CLP). Mice were assigned into 5 groups with varied treatments. Their time of death was recorded every 6 hours after surgery. The wet/dry (W/D) weight ratio of the lung was measured. Observation of lung tissues was conducted by hematoxylin and eosin (HE) staining. Protein concentration in bronchoalveolar lavage fluid (BALF), levels of inflammatory cytokines, and production of reactive oxygen species (ROS) were detected by bicinchoninic acid (BCA), enzyme-linked immunosorbent assay, and dihydroethidium (DHE) staining, respectively. Endoplasmic reticulum (ER) stress-related genes, heme oxygenase-1 (HO-1), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) levels were quantified by western blot.
RESULTS: GA remarkably elevated survival rate and mitigated lung injury (p < 0.05). CLP markedly increased the W/D weight ratio and BALF protein concentration, while GA did the opposite (p < 0.05). CLP promoted interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), phosphorylation of eIF2α (p-eIF2α), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), the phosphorylation level of JAK/STAT3, along with DHE intensity, while GA showed opposite effects (p < 0.01). Additionally, GA markedly enhanced the HO-1 level (p < 0.05).
CONCLUSION: GA holds promise for future improvements in treating sepsis-induced ALI.