An Oxidized Mogrol Derivative Alleviates LPS-Induced Acute Lung Injury in Association with Reduced NLRP3 Inflammasome-Associated Inflammatory Responses in Mice
- 1College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China
- 2Guangxi Academy of Sciences, Nanning 530007, China
- 3Guangxi Engineering Research Center for High-Value Utilization of Guangxi-Produced Authentic Medicinal Herbs, Guangxi University of Chinese Medicine, Nanning 530200, China
Abstract
Acute lung injury (ALI) is a severe inflammatory pulmonary disorder with high morbidity and limited treatment options available in clinical settings. Mogrosides, natural products derived from Siraitia grosvenorii, have been shown to exhibit protective effects against ALI, but structural optimization of their aglycone moiety, mogrol, may provide opportunities to improve pharmacological efficacy. In this study, oxidized mogrol derivatives (MG-COOH and MG-CHO) were synthesized, and their anti-inflammatory activities were initially compared with those of natural mogrosides in lipopolysaccharide (LPS)-stimulated MH-S cells. MG-COOH exhibited pronounced anti-inflammatory activity and was designated for comprehensive analysis of its protective potential and underlying mechanisms in the LPS-induced ALI model. MG-COOH effectively alleviated LPS-induced injury in lung, decreased pro-inflammatory cytokine release, and reduced oxidative stress, showing a tendency toward greater efficacy relative to natural mogrosides at equimolar doses. Transcriptomic analysis indicated that MG-COOH modulated genes involved in the HIF-1, JAK-STAT, MAPK, PI3K-Akt, NF-κB, NOD-like receptor, and Toll-like receptor signaling pathways. Furthermore, MG-COOH reduced the expression of NLRP3, ASC, caspase-1, and IL-1β mRNA and protein in lung. In conclusion, the oxidized mogrol derivative MG-COOH exhibits pronounced anti-ALI activity, which is associated with reduced NLRP3 inflammasome-related inflammatory responses in the lung, which serves as a pivotal node in multiple inflammatory signaling cascades.
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BibTeX
@article{feng2026oxidized,
title = {{An Oxidized Mogrol Derivative Alleviates LPS-Induced Acute Lung Injury in Association with Reduced NLRP3 Inflammasome-Associated Inflammatory Responses in Mice}},
author = {Guizeng Feng and Yinting Tuo and Jian Su and Feng Huang and Dianpeng Li and Lini Huo and Xing Xia},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219584},
url = {https://www.mdpi.com/1422-0067/27/21/9584},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An Oxidized Mogrol Derivative Alleviates LPS-Induced Acute Lung Injury in Association with Reduced NLRP3 Inflammasome-Associated Inflammatory Responses in Mice
AU - Guizeng Feng
AU - Yinting Tuo
AU - Jian Su
AU - Feng Huang
AU - Dianpeng Li
AU - Lini Huo
AU - Xing Xia
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219584
UR - https://www.mdpi.com/1422-0067/27/21/9584
AB - Acute lung injury (ALI) is a severe inflammatory pulmonary disorder with high morbidity and limited treatment options available in clinical settings. Mogrosides, natural products derived from Siraitia grosvenorii, have been shown to exhibit protective effects against ALI, but structural optimization of their aglycone moiety, mogrol, may provide opportunities to improve pharmacological efficacy. In this study, oxidized mogrol derivatives (MG-COOH and MG-CHO) were synthesized, and their anti-inflammatory activities were initially compared with those of natural mogrosides in lipopolysaccharide (LPS)-stimulated MH-S cells. MG-COOH exhibited pronounced anti-inflammatory activity and was designated for comprehensive analysis of its protective potential and underlying mechanisms in the LPS-induced ALI model. MG-COOH effectively alleviated LPS-induced injury in lung, decreased pro-inflammatory cytokine release, and reduced oxidative stress, showing a tendency toward greater efficacy relative to natural mogrosides at equimolar doses. Transcriptomic analysis indicated that MG-COOH modulated genes involved in the HIF-1, JAK-STAT, MAPK, PI3K-Akt, NF-κB, NOD-like receptor, and Toll-like receptor signaling pathways. Furthermore, MG-COOH reduced the expression of NLRP3, ASC, caspase-1, and IL-1β mRNA and protein in lung. In conclusion, the oxidized mogrol derivative MG-COOH exhibits pronounced anti-ALI activity, which is associated with reduced NLRP3 inflammasome-related inflammatory responses in the lung, which serves as a pivotal node in multiple inflammatory signaling cascades.
SN - 1422-0067
ER -