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Glycyrrhizic Acid Alleviates Lipopolysaccharide (LPS)-Induced Acute Lung Injury by Regulating Angiotensin-Converting Enzyme-2 (ACE2) and Caveolin-1 Signaling Pathway

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Abstract—

Acute lung injury (ALI) is mainly caused by severe infection, shock, trauma, and burn, which causes the extensive release of inflammatory factors and other mediators. As a major bioactive constituent of traditional Chinese herb licorice, glycyrrhizic acid (GA) plays an important effect on inflammatory regulation. Nevertheless, the exact mechanism of this effect remains unclear. The present study aims to explore the potential protective effect of GA on LPS-induced ALI. Our results showed that GA significantly attenuated LPS-induced ALI and decreased the production of inflammatory factors, including IL-1β, MCP-1, COX2, HMGB1, and adhesion molecules, such as E-selectin, VCAM-1, and modulated expression of angiotensin-converting enzyme 2 (ACE2). Moreover, treatment of ACE2 inhibitor (MLN-4760) reversed the effects of GA on the secretion of pro-inflammatory factors in ALI. Additionally, GA exerts its protective effect by regulating the ACE2 and caveolin-1/NF-κB signaling pathway. In conclusion, this study showed that GA alleviated LPS-induced ALI by upregulating ACE2 and inhibiting the caveolin-1/NF-κB signaling pathway.

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Abbreviations

ALI:

Acute lung injury

ACE2:

Angiotensin converting enzyme 2

COX-2:

Cyclooxygenase-2

GA:

Glycyrrhizic acid

HUVECs:

Human umbilical vein endothelial cells

HMGB1:

High-mobility group box 1

IL-1β:

Interleukin-1β

LPS:

Lipopolysaccharide

MCP-1:

Monocyte chemotactic factor 1

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Acknowledgements

We are very grateful to the Hunan Normal University School of Medicine for providing the laboratory facilities.

Funding

This work was supported by Hunan Provincial Innovation Foundation for Postgraduate (CX20190406), National Natural Science Foundation of China (No. 81100054), Hunan Natural Science Foundation (No. 2018JJ2255), and Hunan Natural Science Foundation Joint Project of Science and Health (No. 2018JJ6052).

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Author notes

  1. Yangye Chen and Lihua Qu contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, Hunan Normal University School of Medicine, 371 TongZiPo Road, Changsha, 410013, Hunan, China

    Yangye Chen, Lihua Qu, Yi Li & Li Shen

  2. Department of Immunology, Hunan Normal University School of Medicine, 371 TongZiPo Road, Changsha, 410013, Hunan, China

    Ran Zhang

  3. Department of Pathogenic Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Lihua Qu

  4. School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210013, China

    Chao Chen

  5. Department of Ultrasonography, The Third Xiangya Hospital of Central South University, Changsha, 410013, China

    Wei He

  6. Department of Physiology and Department of Immunology, Hunan Normal University School of Medicine, 371 TongZiPo Road, Changsha, 410013, Hunan, China

    Li Shen & Ran Zhang

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  1. Yangye Chen
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Contributions

Li Shen and Ran Zhang presented the concept of manuscript and edited it. Yangye Chen and Lihua Qu wrote the manuscript and data analysis. Yi Li, Chao Chen, and Wei He contributed to the editing of the manuscript and data acquisition. All the authors contributed to the article and approved the final manuscript.

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Chen, Y., Qu, L., Li, Y. et al. Glycyrrhizic Acid Alleviates Lipopolysaccharide (LPS)-Induced Acute Lung Injury by Regulating Angiotensin-Converting Enzyme-2 (ACE2) and Caveolin-1 Signaling Pathway. Inflammation 45, 253–266 (2022). https://doi.org/10.1007/s10753-021-01542-8

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