Genipin protects rats against lipopolysaccharide-induced acute lung injury by reinforcing autophagy.

Abstract

Although the protective effects of genipin against acute lung injury (ALI) have been described previously, the associated mechanism remains unclear. We have previously reported that genipin exerts its pharmacological effects by regulating autophagy. Here, we hypothesized that the up-regulation of autophagy may contribute to the protective effects exhibited by genipin against ALI. In the present study, ALI was induced by intratracheal LPS administration in rats. Genipin treatment significantly reduced LPS-induced lung injury as evidenced by improved histopathology, decreased lung edema, total cells, and protein concentration in the bronchoalveolar lavage fluid (BALF). This protection was inhibited by 3-methyladenine (3-MA), an inhibitor of autophagy. Genipin treatment reduced the expression of P62 and increased the expression of Beclin-1 and LC3II, indicating increased autophagy. Genipin treatment also alleviated LPS-induced cell apoptosis (down-regulation of Bax, up-regulation of Bcl-2, and decreased number of terminal deoxynucleotidyl transferase dUTP nick end label-positive cells) and oxidative stress (increased SOD and decreased MDA content) in the lung. Furthermore, genipin attenuated LPS-induced production of TNF-α, IL-1β, and IL-6 in the lung and BALF. These protective effects induced by genipin were reversed by 3-MA treatment, indicating that autophagy was involved in the protective effects exerted by genipin against inflammation and apoptosis in ALI. In A549 cells incubated with LPS for 6 h, genipin treatment increased the number of GFP-LC3 punctae. 3-MA prevented the protective effects of genipin against mitochondrial dysfunction and cell death. These findings suggest that genipin protects against apoptosis and inflammation in LPS-induced ALI by promoting autophagy.

• Authors: Zhijie Zhang, Xue Wang, Chengzhou Ma, Zhiwang Li, Huayong Chen, Zhiming Zhang, Tao Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 72 Pg. 21-30 (Jul 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30959368 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Iridoids
• Lipopolysaccharides
• Protective Agents
• genipin

Topics

• A549 Cells
• Acute Lung Injury (drug therapy, immunology, pathology)
• Animals
• Autophagy (drug effects)
• Bronchoalveolar Lavage Fluid (immunology)
• Cell Survival (drug effects)
• Cytokines (immunology)
• Humans
• Iridoids (pharmacology, therapeutic use)
• Lipopolysaccharides
• Lung (drug effects, pathology)
• Male
• Protective Agents (pharmacology, therapeutic use)
• Rats, Sprague-Dawley