Glycyrrhizic acid ameliorates LPS-induced acute lung injury by regulating autophagy through the PI3K/AKT/mTOR pathway.
Lihua Qu, Chao Chen, Wei He, Yangye Chen, Yi Li, Yi Wen, Sichun Zhou, Yiqun Jiang, Xiaoping Yang, Ran Zhang, Li Shen
Author Information
Lihua Qu: Department of Physiology, Hunan Normal University School of Medicine Changsha 410013, China.
Chao Chen: Department of Pathology and Key Laboratory of Cancer Stem Cells and Translational Medicine, Hunan Normal University School of Medicine Changsha 410013, China.
Wei He: Department of Ultrasonography, The Third Xiangya Hospital of Central South University Changsha 410013, China.
Yangye Chen: Department of Physiology, Hunan Normal University School of Medicine Changsha 410013, China.
Yi Li: Department of Physiology, Hunan Normal University School of Medicine Changsha 410013, China.
Yi Wen: Department of Pharmacy and Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University School of Medicine Changsha 410013, China.
Sichun Zhou: Department of Pharmacy and Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University School of Medicine Changsha 410013, China.
Yiqun Jiang: Department of Physiology, Hunan Normal University School of Medicine Changsha 410013, China.
Xiaoping Yang: Department of Pharmacy and Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University School of Medicine Changsha 410013, China.
Ran Zhang: Department of Immunology, Hunan Normal University School of Medicine Changsha 410013, China.
Li Shen: Department of Physiology, Hunan Normal University School of Medicine Changsha 410013, China.
Acute lung injury (ALI) is a major pathological issue characterized by serious inflammatory response, and a major clinically critical illness with high morbidity and mortality. Glycyrrhizic acid (GA) is a major bioactive constituent isolated from traditional Chinese herb licorice, which has been reported to have positive effects on inflammation. Nevertheless, the effects of GA on lipopolysaccharide (LPS)-treated ALI in mice have not been reported. The purpose of our study is to investigate the inhibitory effects of GA on ALI treated by LPS and to elucidate its possible mechanisms. We found that GA significantly attenuated lung injury and decreased the production of inflammatory factors TNF-α, IL-1β, and HMGB1 with LPS treatment. GA induced autophagy which was showed by enhanced number of autophagosomes through upregulating the protein levels of LC3-II/I and Beclin-1 and downregulating SQSTM1/P62. Moreover, pre-treatment of 3-Methyladenine (3-MA), an autophagy inhibitor, reversed the inhibiting effects of GA on the secretion of inflammatory factors in ALI. The PI3K/AKT/mTOR pathway was associated with GA-induced autophagy under ALI induced by LPS. In conclusion, this study indicated that GA inhibited the production of inflammatory factors in LPS-induced ALI by regulating the PI3K/AKT/mTOR pathway related autophagy, which may provide a novel therapeutic perspective of GA in ameliorating ALI.
