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Momordicoside G Regulates Macrophage Phenotypes to Stimulate Efficient Repair of Lung Injury and Prevent Urethane-Induced Lung Carcinoma Lesions
- Source :
- Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 10 (2019)
- Publication Year :
- 2018
-
Abstract
- Momordicoside G is a bioactive component from Momordica charantia, this study explores the contributions of macrophages to the effects of momordicoside G on lung injury and carcinoma lesion. In vitro, when administered at the dose that has no effect on cell viability in M2-like macrophages, momordicoside G decreased ROS and promoted autophagy and thus induced apoptosis in M1-like macrophages with the morphological changes. In the urethane-induced lung carcinogenic model, prior to lung carcinoma lesions, urethane induced obvious lung injury accompanied by the increased macrophage infiltration. The lung carcinoma lesions were positively correlated with lung tissue injury and macrophage infiltration in alveolar cavities in the control group, these macrophages showed mainly a M1-like (iNOS+/CD68+) phenotype. ELISA showed that the levels of IL-6 and IL-12 were increased and the levels of IL-10 and TGF-β1 were reduced in the control group. After momordicoside G treatment, lung tissue injury and carcinoma lesions were ameliorated with the decreased M1-like macrophages and the increased M2-like (arginase+/CD68+) macrophages, whereas macrophage depletion by liposome-encapsulated clodronate (LEC) decreased significantly lung tissue injury and carcinoma lesions and also attenuated the protective efficacy of momordicoside G. The M2 macrophage dependent efficacy of momordicoside G was confirmed in a LPS-induced lung injury model in which epithelial closure was promoted by the transfer of M2-like macrophages and delayed by the transfer of M1-like macrophages. To acquire further insight into the underlying molecular mechanisms by which momordicoside G regulates M1 macrophages, we conduct a comprehensive bioinformatics analysis of momordicoside G relevant targets and pathways involved in M1 macrophage phenotype. This study suggests a function of momordicoside G, whereby it selectively suppresses M1 macrophages to stimulate M2-associated lung injury repair and prevent inflammation-associated lung carcinoma lesions.
- Subjects :
- 0301 basic medicine
Lung injury
Lesion
03 medical and health sciences
0302 clinical medicine
macrophage phenotypes
medicine
Carcinoma
Macrophage
Pharmacology (medical)
lung injury
Original Research
Pharmacology
Lung
injury repair
business.industry
CD68
lcsh:RM1-950
M2 Macrophage
medicine.disease
030104 developmental biology
medicine.anatomical_structure
lcsh:Therapeutics. Pharmacology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
momordicoside G
medicine.symptom
business
carcinoma lesions
Subjects
Details
- ISSN :
- 16639812
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in pharmacology
- Accession number :
- edsair.doi.dedup.....50ecd9050ab3b304c69292ed7cd83a86